| mechanism | treatment | Demonstrated benefit and harm | k | | | |
|---|
| All mechanism | serelaxin | versus No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| RELAX-AHF, 2013 | serelaxin vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| RELAX-AHF, 2013 | 48-h intravenous infusions of placebo or serelaxin (30 ìg/kg per day) within 16 h from presentation (n=-9) vs. placebo (on top stnadard care) (n=-9) | patients admitted to hospital for acute heart failure | Sample size: -9/-9 Primary endpoint: FU duration: |
|
| angiotensin-Converting Enzyme Inhibitors | benazepril | versus placebo or no treatment No demonstrated result for efficacy benazepril inferior to placebo in terms of NYHA class improvement in Colfer, 1992 | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Colfer, 1992 | benazepril vs placebo | | NYHA class improvement 2.18 [1.02; 4.66] | all cause death or hospitalisation 0.25 [0.05; 1.35] | | McGany, 1991 | benazepril vs control | | | all cause death or hospitalisation 0.92 [0.31; 2.69] |
| Trial | Treatments | Patients | Method |
|---|
| Colfer, 1992 | benazepriltitrated up to 20mg daily (n=114) vs. placebo (n=58) | Patients with chronic New York Heart Association class II to IV symptoms of CHF and an ejection fraction by radionuclide scanning of less than or equal to 35% | double blind Sample size: 114/58 Primary endpoint: exercise duration FU duration: 12-week | | McGany, 1991 | (n=29) vs. (n=32) | | Sample size: 29/32 Primary endpoint: FU duration: |
|
| angiotensin-Converting Enzyme Inhibitors | captopril | versus placebo or no treatment No demonstrated result for efficacy captopril inferior to placebo in terms of NYHA class improvement in Captopril Digoxin Multicenter Research Group, 1988 | 8 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Magnani, 1986 | captopril vs placebo | | | | | Bussmann, 1987 | captopril vs placebo | | | Death 0.61 [0.12; 3.00] | | Captopril Digoxin Multicenter Research Group, 1988 | captopril vs placebo | | NYHA class improvement 1.88 [1.20; 2.94] | all cause death or hospitalisation 0.87 [0.56; 1.34] | | Barabino, 1991 | captopril vs placebo | all cause death or hospitalisation 0.50 [0.31; 0.82] | | | | Munich MHFT (Kleber), 1992 | captopril vs placebo | | | Death 1.05 [0.63; 1.74] all cause death or hospitalisation 1.00 [1.00; 1.00] | | captopril vs placebo | | | | | captopril vs placebo | | | | | captopril vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Magnani, 1986 | captopril 25 mg t.i.d. (n=48) vs. placebo (n=46) | patients on digitalis treatment for chronic congestive heart failure (NYHA class II-III) | double blind Sample size: 48/46 Primary endpoint: Clinical status, exercise capacity, cardiac dimensions and performance FU duration: 1 year | | Bussmann, 1987 | captopril (n=12) vs. placebo (n=11) | patients with severe heart failure (NYHA classes III and IV) on treatment with digitalis and diuretics | double blind Parallel groups Sample size: 12/11 Primary endpoint: FU duration: 6 months | | Captopril Digoxin Multicenter Research Group, 1988 | captopril (n=104) vs. placebo (n=100) | patients with mild to moderate heart failure | double blind Sample size: 104/100 Primary endpoint: FU duration: | | Barabino, 1991 | captopril (37.5-75 mg/day) (n=52) vs. placebo (n=49) | old patients (>75y) under treatment with digitalis and/or diuretics | double blind Sample size: 52/49 Primary endpoint: FU duration: 6 months | | Munich MHFT (Kleber), 1992 | captopril 25 mg twice a day (n=83) vs. placebo
(n=87)
| patients with congestive heart failure New
York Heart Association (NYHA) functional
class I-III on standard treatment
| Double blind Parallel groups Sample size: 83/87 Primary endpoint: Progression of heart failure to NYHA class IV FU duration: 2.7y (median)
| | Magnani, 1990 | captopril (n=16) vs. placebo (n=16) | patients with congestive heart failure | double blind Cross over Sample size: 16/16 Primary endpoint: hemodynamic response to static exercise FU duration: | | CMRG, 1983 | captopril (n=50) vs. placebo (n=42) | patients with heart failure refractory to digitalis and diuretic therapy | double blind Sample size: 50/42 Primary endpoint: FU duration: 12 weeks | | Cilazapril-Captopril Multi-centre Group (capt vs pbo), 1995 | cilazapril 1-2.5 mg once daily (n=108) vs. placebo
(n=114) | patients with chronic heart failure (New York Heart Association classes II-IV)
| double blind Parallel groups Sample size: 108/114 Primary endpoint: exercise tolerance FU duration: 12 weeks
|
|
| angiotensin-Converting Enzyme Inhibitors | captopril | versus angiotensin-converting enzyme inhibitors No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| captopril vs enalapril | | | |
| Trial | Treatments | Patients | Method |
|---|
| packer, 1986 | captopril 150 mg/d (n=21) vs. enalapril 40mg/d (n=21) | patient with severe chronic heart failure | open Parallel groups Sample size: 21/21 Primary endpoint: none FU duration: 1-3 months |
|
| angiotensin-Converting Enzyme Inhibitors | cilazapril | versus placebo or no treatment No demonstrated result for efficacy | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Drexler, 1989 | cilazapril vs placebo | | | all cause death or hospitalisation 0.91 [0.16; 5.30] NYHA class improvement ∞ [NaN; ∞] | | cilazapril vs placebo | | | | | cilazapril vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Drexler, 1989 | cilazapril (n=11) vs. placebo (n=10) | patients with chronic heart failure | double blind Sample size: 11/10 Primary endpoint: FU duration: 3 months | | Dosseger, 1993 | cilazapril titrated up to 2.5 mg/d (n=7) vs. placebo (n=35) | patients with chronic heart failure (NYHA class II to IV) stabilized on digitalis and/or diuretics | double blind Sample size: 7/35 Primary endpoint: exercise tolerance FU duration: 12 weeks | | Cilazapril-Captopril Multi-centre Group, 1995 | cilazapril 1-2.5 mg once daily (n=221) vs. placebo (n=114) | patients with chronic heart failure (New York Heart Association classes II-IV) | double blind Parallel groups Sample size: 221/114 Primary endpoint: exercise tolerance FU duration: 12 weeks |
|
| angiotensin-Converting Enzyme Inhibitors | cilazapril | versus angiotensin-converting enzyme inhibitors No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| cilazapril vs captopril | | | |
| Trial | Treatments | Patients | Method |
|---|
| Cilazapril-Captopril Multi-centre Group (cila vs capt), 1995 | cilazapril 1-2.5 mg once daily (n=221) vs. captopril 25-50mg three times daily (n=108)
| patients with chronic heart failure (New York Heart Association classes II-IV)
| double blind Parallel groups Sample size: 221/108 Primary endpoint: exercise tolerance FU duration: 12 weeks
|
|
| angiotensin-Converting Enzyme Inhibitors | enalapril | versus placebo or no treatment No demonstrated result for efficacy enalapril inferior to placebo in terms of Death in SOLVD treatment, 1991 enalapril inferior to placebo in terms of Hospitalisation in SOLVD treatment, 1991 enalapril inferior to placebo in terms of NYHA class improvement in CONSENSUS, 1987 | 12 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| SOLVD treatment, 1991 | enalapril vs placebo | all cause death or hospitalisation 0.83 [0.77; 0.90] | Death 0.89 [0.80; 0.98] Hospitalisation 0.71 [0.63; 0.79] | | | enalapril vs placebo | | | | | Cleland, 1985 | enalapril vs placebo | | | all cause death or hospitalisation NaN [NaN; NaN] | | Rucinska-b (enalapril), 1991 | enalapril vs control | | | all cause death or hospitalisation 0.00 [0.00; NaN] | | CONSENSUS, 1987 | enalapril vs placebo | | NYHA class improvement 7.94 [1.86; 33.81] | all cause death or hospitalisation 0.97 [0.84; 1.12] | | Enalapril CHF investigators, 1987 | enalapril vs control | | | all cause death or hospitalisation 0.52 [0.18; 1.47] | | Dickstein, 1991 | enalapril vs placebo | | | all cause death or hospitalisation 0.00 [0.00; NaN] | | Rucinska-a (enalapril), 1991 | enalapril vs control | | | all cause death or hospitalisation 0.49 [0.09; 2.56] | | enalapril vs placebo | | | | | enalapril vs placebo | | | | | enalapril vs placebo | | | | | enalapril vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| SOLVD treatment, 1991 | Enalapril initial dose 2·5 or 5 mg twice daily up to 10 mg twice daily (n=1285) vs. placebo
(n=1284) | MI >1 month,Congestive HF, LVEF <=35% | Double blind Parallel groups Sample size: 1285/1284 Primary endpoint: FU duration: 3.5 y | | SOLVD prevention, 1992 | Enalapril initial dose 2·5 or 5 mg twice daily up to 10 mg twice daily (n=2111) vs. placebo
(n=2117) | MI >1 month,No treatment for CHF, LVEF <=35% | double blind Parallel groups Sample size: 2111/2117 Primary endpoint: FU duration: 3.1 y | | Cleland, 1985 | enalapril titrated up to 40mg once daily (n=10) vs. placebo (n=10) | patients with New York Heart Association functional class II to IV heart failure who were clinically stable on digoxin and diuretic therapy | double blind Cross over Sample size: 10/10 Primary endpoint: FU duration: 8 weeks | | Rucinska-b (enalapril), 1991 | (n=55) vs. (n=55) | | Sample size: 55/55 Primary endpoint: FU duration: | | CONSENSUS, 1987 | enalapril (2.5 to 40 mg per day) (n=127) vs. placebo (n=126) | severe congestive heart failure (New York Heart Association [NYHA] functional class IV) | double blind Parallel groups Sample size: 127/126 Primary endpoint: mortality FU duration: 188 days | | Enalapril CHF investigators, 1987 | (n=126) vs. (n=130) | | Sample size: 126/130 Primary endpoint: FU duration: | | Dickstein, 1991 | enalapril (n=20) vs. placebo (n=21) | men with symptomatic heart failure (functional class II or III) and documented myocardial infarction greater than 6 months previously | double blind Sample size: 20/21 Primary endpoint: exercise performance FU duration: 48 weeks | | Rucinska-a (enalapril), 1991 | (n=67) vs. (n=65) | | Sample size: 67/65 Primary endpoint: FU duration: | | Sharpe, 1984 | enalapril 5mg twice day (n=18) vs. placebo (n=18) | patients with New York Heart Association functional class II to III heart failure who were clinically stable on digoxin and diuretic therapy | double blind Sample size: 18/18 Primary endpoint: FU duration: 3 months | | McGrath, 1985 | enalapril (n=13) vs. placebo (n=12) | patients with chronic congestive cardiac failure | double blind Sample size: 13/12 Primary endpoint: FU duration: 12 week | | Chrysant, 1985 | enalapril (n=-9) vs. placebo (n=-9) | patients with congestive heart failure (CHF), New York Heart Association class II-III | double blind Sample size: -9/-9 Primary endpoint: FU duration: 14 weeks | | CASSIS (enalapril), 1995 | enalapril 5-10mg daily (n=48) vs. placebo (n=48) | patients with chronic congestive heart failure of NYHA classes II-IV | double blind Parallel groups Sample size: 48/48 Primary endpoint: exercise tolerance FU duration: 12 weeks |
|
| angiotensin-Converting Enzyme Inhibitors | enalapril | versus angiotensin-converting enzyme inhibitors No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| enalapril vs enalapril | | | | | enalapril vs enalapril | | | |
| Trial | Treatments | Patients | Method |
|---|
| NETWORK (2.5 bid vs 10 bid), 1998 | enalapril 2.5 mg twice daily (n=506) vs. enalapril 10 mg twice daily (n=516) | patients with NYHA II-IV heart failure | double blind Parallel groups Sample size: 506/516 Primary endpoint: death, hospitalization, worsening HF FU duration: 6 months | | NETWORK (5 bid vs 10 bid), 1998 | enalapril 5 mg twice daily
(n=510) vs. enalapril 10 mg twice daily
(n=516)
| patients with NYHA II-IV heart failure
| double blind Parallel groups Sample size: 510/516 Primary endpoint: death, hospitalization, worsening HF FU duration: 6 months
|
|
| angiotensin-Converting Enzyme Inhibitors | enalapril | versus vasodilators No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| enalapril vs hydralazine+ISDN | | | |
| Trial | Treatments | Patients | Method |
|---|
| V-HeFT II, 1991 | enalapril 20mg daily
(n=403) vs. hydralazine 300 mg plus isosorbide dinitrate 160 mg daily
(n=401)
| men with chronic congestive heart failure and cardiac dilatation (CT ratio>0.55) or LVEF <45% in association with reduced exercise tolerance and diuretic therapy
| double blind Parallel groups Sample size: 403/401 Primary endpoint: death FU duration: 2.5y (range 0.5-5.7y)
|
|
| angiotensin-Converting Enzyme Inhibitors | fosinopril | versus placebo or no treatment No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| fosinopril vs placebo | | | | | fosinopril vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Brown, 1995 | fosinopril 10 or 20 mg/day (n=116) vs. placebo (n=125) | patients with chronic congestive heart failure (NYHA II-III) not taking digitalis | double blind Sample size: 116/125 Primary endpoint: exercise tolerance FU duration: 24 weeks | | FEST (Erhardt), 1996 | fosinopril 40 mg once daily titrated (n=155) vs. placebo (n=153) | patients with mild to moderately severe heart failure (NYHA II-III) | double blind Sample size: 155/153 Primary endpoint: maximal bicycle exercise time FU duration: 12 weeks |
|
| angiotensin-Converting Enzyme Inhibitors | lisinopril | versus placebo or no treatment No demonstrated result for efficacy | 5 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Zwehl, 1990 | lisinopril vs control | | | all cause death or hospitalisation 0.84 [0.20; 3.43] | | Giles, 1990 | lisinopril vs control | | | all cause death or hospitalisation 0.32 [0.09; 1.10] | | Rucinska-c (lisinopril), 1000 | lisinopril vs control | | | all cause death or hospitalisation 1.07 [0.07; 16.32] | | Gilbert, 1993 | lisinopril vs placebo | | | all cause death or hospitalisation NaN [NaN; NaN] | | lisinopril vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Zwehl, 1990 | (n=183) vs. (n=92) | | Sample size: 183/92 Primary endpoint: FU duration: | | Giles, 1990 | (n=130) vs. (n=63) | | Sample size: 130/63 Primary endpoint: FU duration: | | Rucinska-c (lisinopril), 1000 | (n=28) vs. (n=30) | | Sample size: 28/30 Primary endpoint: FU duration: | | Gilbert, 1993 | lisinopril (n=14) vs. placebo (n=14) | subjects with heart failure | double blind Cross over Sample size: 14/14 Primary endpoint: FU duration: 12 weeks | | International Study Group (Lewis), 1989 | lisnopril titrated up to 10mg daily (n=87) vs. placebo (n=43) | patients with congestive heart failure NYHA II-IV | double blind Parallel groups Sample size: 87/43 Primary endpoint: exercise tolerance FU duration: 12 weeks |
|
| angiotensin-Converting Enzyme Inhibitors | lisinopril | versus angiotensin-converting enzyme inhibitors No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| lisinopril vs lisinopril | | | |
| Trial | Treatments | Patients | Method |
|---|
| ATLAS, 1999 | lisinopril low dose 2.5-5 mg daily (n=1596) vs. lisnopril high dose 32.5-35 mg daily (n=1568) | patients with New York Heart Association class II to IV heart failure
and an ejection fraction <=30% | double blind Parallel groups Sample size: 1596/1568 Primary endpoint: all cause mortality FU duration: 39 to 58 months |
|
| angiotensin-Converting Enzyme Inhibitors | perindopril | versus placebo or no treatment No demonstrated result for efficacy perindopril inferior to placebo in terms of NYHA class improvement in Lechat, 1993 perindopril inferior to placebo in terms of Hospitalisation in PEP CHF, 2006 | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Lechat, 1993 | perindopril vs placebo | | NYHA class improvement 2.03 [1.24; 3.32] | all cause death or hospitalisation 0.00 [0.00; NaN] | | PEP CHF, 2006 | perindopril vs placebo | | Hospitalisation 0.64 [0.43; 0.97] | Death 0.90 [0.47; 1.71] Long term death (1 year) 0.90 [0.47; 1.71] all cause death or hospitalisation 0.69 [0.47; 1.02] |
| Trial | Treatments | Patients | Method |
|---|
| Lechat, 1993 | perindopril, 2 mg once daily (n=61) vs. placebo (n=64) | patients with grade II or III New York Heart Association chronic congestive heart failure on baseline diuretic therapy | double blind Sample size: 61/64 Primary endpoint: FU duration: 3-month | | PEP CHF, 2006 | perindopril, 4 mg/day (n=424) vs. placebo (n=426) | patients aged >=70 years with a diagnosis of heart failure, treated with diuretics and an echocardiogram
suggesting diastolic dysfunction and excluding substantial LV systolic dysfunction or valve disease | double blind Parallel groups Sample size: 424/426 Primary endpoint: all-cause mortality and unplanned heart failure related hospitalization FU duration: 26.2 months (range 12-54.2m) |
|
| angiotensin-Converting Enzyme Inhibitors | quinapril | versus placebo or no treatment No demonstrated result for efficacy | 8 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Riegger, 1990 | vs placebo | | | all cause death or hospitalisation NaN [NaN; NaN] | | Northridge, 1991 | vs placebo | | | all cause death or hospitalisation NaN [NaN; NaN] | | Uprichard-a, 1994 | vs control | | | all cause death or hospitalisation 0.48 [0.04; 5.25] | | Uprichard-b, 1994 | vs control | | | all cause death or hospitalisation 0.65 [0.11; 3.83] | | Uprichard-c, 1994 | vs control | | | all cause death or hospitalisation ∞ [NaN; ∞] | | Rieger, 1991 | vs placebo | | | NYHA class improvement 1.52 [0.95; 2.44] | | Nussberger, 1994 | vs placebo | | | | | Quinapril Heart Failure Trial Investigators, 1993 | vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Riegger, 1990 | quinapril (5mg bid, 10 mg bid, 20mg bid) (n=169) vs. placebo (n=56) | patients with mild to moderate congestive heart failure (CHF) due to arterial hypertension and ischemic heart disease | double-blind Sample size: 169/56 Primary endpoint: FU duration: 12 weeks | | Northridge, 1991 | quinapril 20mg/d (n=32) vs. placebo (n=32) one daily dosing was compared with twice daily dosing in a 3-way crossover placebo controlled trial | patient with mild heart failure | double blind Cross over Sample size: 32/32 Primary endpoint: exercise FU duration: 8 weeks | | Uprichard-a, 1994 | (n=114) vs. (n=110) | | Sample size: 114/110 Primary endpoint: FU duration: | | Uprichard-b, 1994 | (n=105) vs. (n=103) | | Sample size: 105/103 Primary endpoint: FU duration: | | Uprichard-c, 1994 | (n=139) vs. (n=47) | | Sample size: 139/47 Primary endpoint: FU duration: | | Rieger, 1991 | quinalapril 10, 20, or 40 mg/d (n=225) vs. placebo (n=0) | patients with mild to moderate heart failure | double blind Sample size: 225/0 Primary endpoint: exercise tolerance FU duration: 12 weeks | | Nussberger, 1994 | quinapril (2.5, 5 or 10 mg b.i.d.) (n=55) vs. placebo (n=0) | patients with moderate heart failure (ejection fraction < or = 35%) | double blind Parallel groups Sample size: 55/0 Primary endpoint: Humoral changes FU duration: 12 weeks | | Quinapril Heart Failure Trial Investigators, 1993 | quinapril (n=114) vs. placebo (n=110) After > or = 10 weeks of single-blind quinapril therapy, patients were randomized in double-blind fashion to continue quinapril or to receive placebo | patients with New York Heart Association class II or III heart failure | double blind Parallel groups Sample size: 114/110 Primary endpoint: treadmill exercise time FU duration: 16 weeks |
|
| angiotensin-Converting Enzyme Inhibitors | ramipril | versus placebo or no treatment No demonstrated result for efficacy | 7 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Swedberg, 1991 | ramipril vs control | | | all cause death or hospitalisation 0.44 [0.19; 1.03] | | Maass-a, 1991 | ramipril vs placebo | | | all cause death or hospitalisation 1.03 [0.33; 3.25] | | Gordon, 1991 | ramipril vs placebo | all cause death or hospitalisation 0.21 [0.05; 0.93] | | | | Maass-b, 1991 | ramipril vs placebo | | | all cause death or hospitalisation 0.61 [0.28; 1.34] | | Maass-c, 1991 | ramipril vs placebo | | | all cause death or hospitalisation 0.68 [0.12; 3.89] | | Lemarie, 1992 | ramipril vs placebo | | | all cause death or hospitalisation 0.77 [0.18; 3.23] | | ramipril vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Swedberg, 1991 | (n=115) vs. (n=108) | | Sample size: 115/108 Primary endpoint: FU duration: | | Maass-a, 1991 | ramipril (n=87) vs. placebo (n=45) | patients with heart failure | Sample size: 87/45 Primary endpoint: FU duration: | | Gordon, 1991 | ramipril 10mg/d (n=94) vs. placebo (n=98) | patients with herat failure and LVFE<=35% | double blind Parallel groups Sample size: 94/98 Primary endpoint: exercise FU duration: 12 weeks | | Maass-b, 1991 | ramirpil 5 or 10 mg once daily (n=329) vs. placebo (n=171) 3 arms trials (placebo, 5 and 10 mg) | patient with NYHA II-III heart failure and LVFE<=40% | double blind Parallel groups Sample size: 329/171 Primary endpoint: exercise FU duration: 12 weeks | | Maass-c, 1991 | ramipril 10mg once daily (n=47) vs. placebo (n=48) | patient with heart failure with LVFE<=35% | double blind Parallel groups Sample size: 47/48 Primary endpoint: Exercise FU duration: 12 weeks | | Lemarie, 1992 | ramipril 2.5mg twice daily (n=42) vs. placebo (n=43) | patient with NYHA II-III heart failure | double blind Parallel groups Sample size: 42/43 Primary endpoint: Exercise FU duration: 24 weeks | | Gundersen, 1994 | ramipril titrated from 1.25 mg to a maximum of 10 mg once daily (n=104) vs. placebo (n=91) | patients with NYHA II-III CHF, LVFE<=40% and size of the heart >600ml/m2 for mean or >550ml/m2 for women | double blind Parallel groups Sample size: 104/91 Primary endpoint: maximal exercise time FU duration: 12 weeks |
|
| angiotensin-Converting Enzyme Inhibitors | trandolapril | versus placebo or no treatment No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| trandolapril vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Hampton, 1998 | trandolapril titrated up to 4mg/d (n=144) vs. placebo (n=148) | patients with moderate (New York Heart Association Grades II and III) heart failure | double blind Sample size: 144/148 Primary endpoint: Exercise tolerance FU duration: 16 weeks |
|
| angiotensin-receptor blockers | candesartan | versus placebo or control No demonstrated result for efficacy candesartan inferior to placebo in terms of Hypotension in CHARM-Alternative, 2003 candesartan inferior to placebo in terms of Hyperkalaemia in CHARM-Alternative, 2003 candesartan inferior to placebo in terms of Increase in creatinine in CHARM-Alternative, 2003 | 6 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ARCH-J, 2003 | candesartan vs placebo | | | | | CHARM-Alternative, 2003 | candesartan vs placebo | Cardiovascular death or hospital admission for CHF 0.82 [0.73; 0.93] | Hypotension 4.12 [2.00; 8.49] Hyperkalaemia 6.35 [1.88; 21.38] Increase in creatinine 2.30 [1.48; 3.58] | lung cancer 3.34 [0.92; 12.10] prostate cancer 2.67 [0.71; 10.01] breast cancer 1.26 [0.34; 4.64] Cardiovascular death 0.87 [0.74; 1.02] Angioedema ∞ [NaN; ∞] | | Mitrovic et al., 2003 | candesartan vs placebo | Hypotension 0.25 [0.07; 0.97] | | Cardiovascular death 0.63 [0.13; 3.15] | | SPICE, 2000 | candesartan vs placebo | | | all cause death 1.02 [0.26; 3.97] all cause death or hospital admission 0.82 [0.43; 1.56] hospital admission for heart failure 0.69 [0.33; 1.45] Cough 1.05 [0.88; 1.26] hospital admission for any reason 0.69 [0.39; 1.22] | | STRETCH, 1999 | candesartan vs placebo | | | | | CHARM preserved, 2003 | candesartan vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| ARCH-J, 2003 | Candesartan, 8 mg daily (n=148) vs. Placebo (n=144) | patients with chronic heart failure who were not receiving ACE inhibitor therapy | double blind Parallel groups Sample size: 148/144 Primary endpoint: progression of CHF or addition or dose escalation of CHF medications FU duration: 155 d | | CHARM-Alternative, 2003 | candesartan (target dose32 mg once daily) (n=1013) vs. Placebo (n=1015) | patients with symptomatic heart failure and left-ventricular ejection fraction 40% or less who were notreceiving ACE inhibitors because of previous intolerance | double blind Parallel groups Sample size: 1013/1015 Primary endpoint: Cardiovascular death or hospital admission for CHF FU duration: Median, 33.7 mo | | Mitrovic et al., 2003 | Candesartan, 2 mg, 4mg, 8mg, 16mg daily (n=174) vs. Placebo (n=44) | patients with CHF (New York Heart Association
class II or III) with impaired left ventricular function (ejection fraction <=40%) and pulmonary capillary wedge pressure
>=13 mm Hg | double blind Parallel groups Sample size: 174/44 Primary endpoint: hemdodynamic FU duration: 12 wk | | SPICE, 2000 | Candesartan, 16 mg daily (n=179) vs. Placebo (n=91) | patients with chronic heart failure and left ventricular ejection fraction less than 35%, and history of discontinuing an ACE inhibitor because of intolerance | double blind Parallel groups Sample size: 179/91 Primary endpoint: tolerability FU duration: 12 wk | | STRETCH, 1999 | Candesartan, 4 mg, 8mg, 16mg daily (n=633) vs. Placebo (n=211) | Male and female patients 21 to 80 years of age with mild to moderate symptomatic CHF
(NYHA class II or III) | Double blind Parallel groups Sample size: 633/211 Primary endpoint: total exercise time FU duration: 12 wk | | CHARM preserved, 2003 | candesartan target dose 32 mg once daily (n=1514) vs. placebo (n=1509) | patients with NYHA II-IV heart failure and LVEF higher than 40% | double blind Parallel groups Sample size: 1514/1509 Primary endpoint: cardiovascular death or admission to FU duration: 36.6 months |
|
| angiotensin-receptor blockers | candesartan | versus angiotensin-converting enzyme inhibitors No demonstrated result for efficacy candesartan+ACE inhibitor inferior to ACE inhibitor only in terms of Hyperkalaemia in CHARM-Added, 2003 candesartan+ACE inhibitor inferior to ACE inhibitor only in terms of Increase in creatinine in CHARM-Added, 2003 | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| CHARM-Added, 2003 | candesartan+ACE inhibitor vs ACE inhibitor only | | Hyperkalaemia 4.87 [2.39; 9.94] Increase in creatinine 1.92 [1.38; 2.66] | lung cancer 1.71 [0.67; 4.33] prostate cancer 0.77 [0.29; 2.07] Hypotension 1.45 [0.97; 2.15] Angioedema 0.66 [0.11; 3.97] | | RESOLVD (candesartan alone), 1999 | candesartan vs enalapril | | | Hypotension 1.00 [0.11; 9.51] | | RESOLVD association, 1999 | candesartan+ACE inhibitor vs ACE inhibitor only | | | Increase in creatinine ∞ [NaN; ∞] |
| Trial | Treatments | Patients | Method |
|---|
| CHARM-Added, 2003 | Candesartantarget dose 32 mg once daily (n=1276) vs. Placebo (n=1272) | patients with New York Heart Association functional class II–IV CHF and left-ventricular ejection fraction40% or lower, and who were being treated with ACE inhibitors. | double blind Parallel groups Sample size: 1276/1272 Primary endpoint: cardiovascular death or FU duration: Median, 41 mo | | RESOLVD (candesartan alone), 1999 | Candesartan, 4 mg, 8mg, 16mg daily (n=327) vs. Enalapril, 10 mg twice daily (n=109) | Patients with New York Heart Association functional class NYHA
II, III, or IV CHF, 6-minute walk distance (6MWD) >500 m, and ejection fraction (EF) <0.40 | Double blind Parallel groups Sample size: 327/109 Primary endpoint: hemodynamic FU duration: 43 wk | | RESOLVD association, 1999 | Candesartan, 4 mg, 8mg daily, plus enalapril, 10 mg twice daily (n=332) vs. Enalapril, 10 mg twice daily (n=109) | Patients with New York Heart Association functional class NYHA
II, III, or IV CHF, 6-minute walk distance (6MWD) >500 m, and ejection fraction (EF) <0.40 | Parallel groups Sample size: 332/109 Primary endpoint: hemodynamic FU duration: 43 wk |
|
| angiotensin-receptor blockers | irbesartan | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| I-PRESERVE (McMurray), 2008 | ibesartan vs placebo | | | Death from Any Cause, Cardiac Arrest with Resuscitation, Hospitalization for Worsening Heart Failure, or Therapy with Intravenous Inotropes or Vasodilators 0.97 [0.89; 1.05] all cause death 1.02 [0.91; 1.14] Cardiovascular death 1.03 [0.89; 1.19] hospital admission for heart failure 0.96 [0.84; 1.11] hospital admission for any reason 1.02 [0.97; 1.08] death or CV hospitalization 0.97 [0.89; 1.05] Cardiovascular death or hospital admission for CHF 0.97 [0.87; 1.10] |
| Trial | Treatments | Patients | Method |
|---|
| I-PRESERVE (McMurray), 2008 | ibersatan 300mg daily (n=2067) vs. placebo (n=2061) | patients with NYHA
II, III, or IV heart failure and an ejection fraction of at least 45% | double blind Parallel groups Sample size: 2067/2061 Primary endpoint: FU duration: 49.5 months |
|
| angiotensin-receptor blockers | irbesartan | versus angiotensin-converting enzyme inhibitors No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Tonkon et al., 2000 | irbesartan+ACE inhibitor vs ACE inhibitor only | | | |
| Trial | Treatments | Patients | Method |
|---|
| Tonkon et al., 2000 | Irbesartan, 150 mg daily (plus ACE inhibitor) (n=57) vs. Placebo (plus ACE inhibitor) (n=52) | patients with heart failure (New York Heart Association functional class II and III) and left ventricular ejection fraction (LVEF) < or = 40% received stable doses of ACE inhibitors and diuretics | double blind Parallel groups Sample size: 57/52 Primary endpoint: Exercise tolerance FU duration: 12 wk |
|
| angiotensin-receptor blockers | losartan | versus angiotensin receptor blocker No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| HEAAL, 2009 | losartan 150mg vs losartan 50mg | all cause death or hospital admission 0.90 [0.82; 0.99] hospital admission for heart failure 0.87 [0.77; 0.99] | | all cause death 0.94 [0.84; 1.05] Adverse effect leading to treatment discontinuation 1.11 [0.88; 1.39] Hypotension 1.18 [0.61; 2.29] Angioedema ∞ [NaN; ∞] Hyperkalaemia 2.24 [0.69; 7.26] death or CV hospitalization 0.92 [0.84; 1.00] Increase in creatinine 1.33 [0.87; 2.04] |
| Trial | Treatments | Patients | Method |
|---|
| HEAAL, 2009 | losartan 150mg daily (n=1921) vs. losartan 50 mg daily (n=1913) | patients with systolic heart failure who couldn't tolerate ACE inhibitors | double blind Parallel groups Sample size: 1921/1913 Primary endpoint: death, admission for heart failure FU duration: 4.7 y (median) |
|
| angiotensin-receptor blockers | losartan | versus placebo or control No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Losartan Phase III International, 1996 | losartan vs placebo | all cause death 0.17 [0.05; 0.62] | | | | Losartan Phase III U.S., 1995 | losartan vs placebo | | | all cause death 0.48 [0.12; 1.89] |
| Trial | Treatments | Patients | Method |
|---|
| Losartan Phase III International, 1996 | Losartan, 50 mg daily (n=254) vs. Placebo (n=131) | patients with heart failure who had never received ACE inibitors or who had discontinued ACE inhibitors | double blind Parallel groups Sample size: 254/131 Primary endpoint: Exercise FU duration: 12 wk | | Losartan Phase III U.S., 1995 | Losartan, 50 mg daily (n=237) vs. Placebo (n=114) | patients with heart failure who had never received ACE inibitors or who had discontinued ACE inhibitors | double blind Parallel groups Sample size: 237/114 Primary endpoint: Exercise FU duration: 12 wk |
|
| angiotensin-receptor blockers | losartan | versus angiotensin-converting enzyme inhibitors No demonstrated result for efficacy | 7 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Dickstein et al., 1995 | losartan vs enalapril | | | | | ELITE, 1997 | losartan vs captopril | | | Cardiovascular death 0.53 [0.27; 1.03] Hypotension 1.68 [0.56; 5.09] Angioedema 0.00 [0.00; NaN] Hyperkalaemia 0.35 [0.07; 1.72] Increase in creatinine 1.00 [0.65; 1.53] | | ELITE II, 2000 | losartan vs captopril | | | | | Hamroff et al., 1999 | losartan+ACE inhibitor vs ACE inhibitor only | | | | | Lang et al., 1997 | losartan vs enalapril | | | | | Losartan phase II S, 1996 | losartan vs enalapril | | | | | losartan phase II US, 1996 | losartan vs enalapril | | | |
| Trial | Treatments | Patients | Method |
|---|
| Dickstein et al., 1995 | Losartan, 25 mg, 50mg daily (n=108) vs. Enalapril, 10 mg twice daily (n=58) | patients with moderate or severe chronic heart failure in New York Heart Association functional class III or IV and an ejection fraction < or = 35% | double blind Parallel groups Sample size: 108/58 Primary endpoint: clinical status and exercise performance FU duration: 8 wk | | ELITE, 1997 | Losartan titrated to 50 mg once daily (n=352) vs. Captopril,titratedto 50 mg three times daily (n=370) | ACE inhibitor naive patients (aged 65 years or more) with New York HeartAssociation (NYHA) class II–IV heart failure and ejection fractions of 40% or less | Double blind Parallel groups Sample size: 352/370 Primary endpoint: tolerability measure of a persist ing FU duration: 48 wk | | ELITE II, 2000 | Losartan, target dose 50 mg daily (n=1578) vs. Captopril, target dose 50 mg 3 times daily (n=1574) | patients aged 60 years or older with New York Heart Association class II–IV heart failure and ejection fraction of 40% or less. | Double blind Parallel groups Sample size: 1578/1574 Primary endpoint: All-cause mortalityur=na FU duration: median 1.5y | | Hamroff et al., 1999 | Losartan, 50 mg daily (plus ACE inhibitor) (n=16) vs. Placebo (plus ACE inhibitor) (n=17) | patients with severe congestive heart failure (NYHA III-IV) despite treatment with maximally recommended or tolerated doses of ACE inhibitors | double blind Parallel groups Sample size: 16/17 Primary endpoint: exercise capacity FU duration: 6 mo | | Lang et al., 1997 | Losartan titrated to 25 mg ou 50 mg daily (n=78) vs. Enalapril, titrated to 10 mg twice daily (n=38) Three arms: losartan 25mg/d, losaratan 50mg/d and enalapril 20mg/d. The 2 losartan group has been pooled | patients with congestive heart failure (New York Heart Association functionalclasses II to IV) and left ventricular ejection fraction <= 45%previously treated with stable doses of ACE inhibitors and diureticagents, with or without concurrent digitalis and othervasodilators | Double blind Parallel groups Sample size: 78/38 Primary endpoint: maximal treadmill FU duration: 12 wk | | Losartan phase II S, 1996 | losartan 50 or 25 mg/d (n=108) vs. enalapril 10mg twice daily (n=58) | patient with heart failure | double blind Parallel groups Sample size: 108/58 Primary endpoint: exercise FU duration: 8 weeks | | losartan phase II US, 1996 | losartan 25 and 50 mg/d (n=78) vs. enalapril 10mg twice daily (n=38) | patients with heart failure | double blind Parallel groups Sample size: 78/38 Primary endpoint: exercise FU duration: 12 weeks |
|
| angiotensin-receptor blockers | telmisartan | versus angiotensin-converting enzyme inhibitors No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| REPLACE, 2001 | telmisartan vs enalapril | | | |
| Trial | Treatments | Patients | Method |
|---|
| REPLACE, 2001 | Telmisartan, 10 mg, 20mg, 40mg, 80mg daily (n=301) vs. Enalapril, 10 mg twice daily (n=77) | ambulatory patients at least 21 years of age, in sinus rhythm, with chronic moderatesymptomatic heart failure (New York Heart Associatality.tion class II–III) and a left ventricular ejection fraction of 40% or lower | Double blind Parallel groups Sample size: 301/77 Primary endpoint: exercise test durationge FU duration: 12 wk |
|
| angiotensin-receptor blockers | valsartan | versus placebo or control No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Mazayev et al. (vs placebo), 1998 | valsartan vs placebo | | | | | VALIDD, 2007 | valsartan vs no valsartan | | | cancer 5.32 [0.63; 45.15] |
| Trial | Treatments | Patients | Method |
|---|
| Mazayev et al. (vs placebo), 1998 | valsartan 40, 80 or 160 mg twice daily (n=75) vs. Placebo (n=26) | patients with chronic heart failure previously untreated with ACE inhibitors | Double blind Parallel groups Sample size: 75/26 Primary endpoint: pulmonary capillary wedge pressure FU duration: 4 wk | | VALIDD, 2007 | valsartan titrated up to 320 mg once daily (n=186) vs. placebo (n=198) | Patients with hypertension and evidence of diastolic dysfunction | double blind Parallel groups Sample size: 186/198 Primary endpoint: diastolic relaxation velocity FU duration: 38 weeks |
|
| angiotensin-receptor blockers | valsartan | versus angiotensin-converting enzyme inhibitors No demonstrated result for efficacy valsartan+ACE inhibitor inferior to ACE inhibitor only in terms of Adverse effect leading to treatment discontinuation in Val-HeFT, 2001 valsartan+ACE inhibitor inferior to ACE inhibitor only in terms of Increase in creatinine in Val-HeFT, 2001 | 4 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| HEAVEN, 2002 | valsartan vs enalapril | | | | | V-HeFT, 1999 | valsartan+ACE inhibitor vs ACE inhibitor only | | | Hypotension ∞ [NaN; ∞] Hyperkalaemia ∞ [NaN; ∞] Increase in creatinine 1.02 [0.10; 10.75] | | Val-HeFT, 2001 | valsartan+ACE inhibitor vs ACE inhibitor only | Death from Any Cause, Cardiac Arrest with Resuscitation, Hospitalization for Worsening Heart Failure, or Therapy with Intravenous Inotropes or Vasodilators 0.90 [0.83; 0.98] hospital admission for heart failure 0.76 [0.67; 0.86] | Adverse effect leading to treatment discontinuation 1.46 [1.20; 1.77] Increase in creatinine 6.73 [2.36; 19.19] | cancer death 1.00 [0.60; 1.65] all cause death 1.02 [0.91; 1.14] Hypotension 1.68 [0.95; 2.95] | | Mazayev et al. (vs lisinopril, 1998 | valsartan vs Lisinopril | | | |
| Trial | Treatments | Patients | Method |
|---|
| HEAVEN, 2002 | Valsartan, 160 mg daily (n=70) vs. Enalapril, 10 mg twice daily (n=71) | Men and women with mild/moderate heart failure stabilised on an angiotensin-converting enzyme inhibitor and left ventricular ejection fraction 0.45 or less | Double blind Parallel groups Sample size: 70/71 Primary endpoint: exercise capacity, FU duration: 12 wk | | V-HeFT, 1999 | Valsartan 80 mg and 160mg twice daily (plus ACE inhibitor) (n=55) vs. Placebo (plus usual ACE inhibitor) (n=28) | Patients with stable symptomatic congestive heart failure (CHF) receiving long-term ACE inhibitor therapy (NYHA functional class II,III, or IV) and PCWP >or=to 15 mm Hg | Double blind Parallel groups Sample size: 55/28 Primary endpoint: change from baseline in PCWP FU duration: 4 wk | | Val-HeFT, 2001 | Valsartan, 160 mg twice daily (plus ACE inhibitor) (n=2511) vs. Placebo (plus ACE inhibitor) (n=2499) | patients with heart failure of New York Heart Association (NYHA) class II, III, or IV | Double blind Parallel groups Sample size: 2511/2499 Primary endpoint: moratlity and morbidity FU duration: 23 mo | | Mazayev et al. (vs lisinopril, 1998 | Valsartan, 40 mg, 80mg, 160mg twice daily (n=75) vs. lisinopril 10mg once daily (n=15) | patients with chronic heart failure | NA Parallel groups Sample size: 75/15 Primary endpoint: pulmonary capillary wedge pressure FU duration: 4 wk |
|
| antiarrythmic drugs | amiodarone | versus placebo or control No demonstrated result for efficacy | 5 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Hamer, 1989 | amiodarone vs placebo | Arrhythmic/sudden death 0.09 [0.01; 0.72] | | All cause death 0.75 [0.24; 2.31] | | Nicklas, 1991 | amiodarone vs placebo | | | All cause death 1.54 [0.59; 4.02] Arrhythmic/sudden death 1.93 [0.67; 5.55] | | EPAMSA, 1985 | amiodarone vs no treatment | All cause death 0.39 [0.15; 1.00] | | Arrhythmic/sudden death 0.39 [0.12; 1.24] | | GESICA, 1994 | amiodarone vs no treatment | All cause death 0.72 [0.55; 0.95] | | Arrhythmic/sudden death 0.72 [0.45; 1.16] | | STATCHF, 1995 | amiodarone vs placebo | | | All cause death 0.94 [0.71; 1.24] Arrhythmic/sudden death 0.84 [0.57; 1.24] |
| Trial | Treatments | Patients | Method |
|---|
| Hamer, 1989 | amiodarone 200 mg/day (n=34) vs. placebo (n=0) | patients with severe congestive heart failure but no sustained ventricular arrhythmia | double blind Sample size: 34/0 Primary endpoint: LVEF FU duration: 1·63 years | | Nicklas, 1991 | amiodarone 200 mg/day (n=101) vs. placebo (n=0) | patients with ejection fractions less than 30%, New York Heart Association class III or IV symptoms, and frequent but asymptomatic spontaneous ventricular ectopy (Lown class II to V) LVEF <=30% and Lown class 2–5 | double blind Sample size: 101/0 Primary endpoint: FU duration: NA | | EPAMSA, 1985 | amiodarone 400 mg/day (n=66) vs. no treatment (n=61) | patients with reduced left ventricular ejection fraction ( < 35%) and asymptomatic ventricular arrhythmias (Lown classes 2 and 4) LVEF <=35% and Lown class 2–5 | open Sample size: 66/61 Primary endpoint: FU duration: 0·81 years | | GESICA, 1994 | amiodarone 300 mg/day (n=260) vs. no treatment (n=256) | patients with severe heart failure Any two of CTR >0·55, LVEF<=35%, echo LVED >3·2 cm/m2 | open Sample size: 260/256 Primary endpoint: FU duration: 1·10 years | | STATCHF, 1995 | amiodarone 200 mg/day (n=674) vs. placebo (n=0) | patients with symptoms of congestive heart failure, cardiac enlargement, 10 or more premature ventricular contractions per hour, and a left ventricular ejection fraction of 40 percent or less LVEF <=40% and >=10 VPD/h and LVED >=55 mm or CTR >0·55 | double blind Sample size: 674/0 Primary endpoint: overall mortality FU duration: 2·15 years |
|
| antiarrythmic drugs | amiodarone | versus No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| AMIOVIRT, 2003 | amiodarone vs ICD | | | All cause death 1.14 [0.41; 3.17] Arrhythmic/sudden death 1.96 [0.18; 20.97] |
| Trial | Treatments | Patients | Method |
|---|
| AMIOVIRT, 2003 | amiodarones (n=52) vs. implantable cardioverter-defibrillatorag (n=51) | patients with
nonischemic dilated cardiomyopathy, asymptomatic nonsustained ventricular tachycardia, and left ventricular ejection fraction <=0.35 | Parallel groups Sample size: 52/51 Primary endpoint: total mortality FU duration: 2 y |
|
| antiarrythmic drugs | dronedarone | versus placebo or control No demonstrated result for efficacy dronedarone inferior to placebo in terms of All cause death in ANDROMEDA, 2008 | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ANDROMEDA, 2008 | dronedarone vs placebo | | All cause death 2.13 [1.09; 4.16] | death from any cause or hospitalization 1.35 [0.93; 1.98] Arrhythmic/sudden death 1.70 [0.63; 4.63] |
| Trial | Treatments | Patients | Method |
|---|
| ANDROMEDA, 2008 | dronedarone 400mg twice daily (n=310) vs. placebo (n=317) | patients hospitalized with symptomatic heart failure and severe left ventricular systolic dysfunction | double blind Parallel groups Sample size: 310/317 Primary endpoint: death, hospitalization for HF FU duration: median 2 months |
|
| antithrombotics | aspirin | versus placebo or no treatment No demonstrated result for efficacy aspirin inferior to no treatment in terms of All-cause hospitalisation in WASH (aspirin), 2004 | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| WASH (aspirin), 2004 | aspirin vs no treatment | | All-cause hospitalisation 1.31 [1.02; 1.70] | death 1.40 [0.85; 2.29] bleeding ∞ [NaN; ∞] stroke (fatal and non fatal) 1.09 [0.16; 7.56] MI (fatal or non fatal) 1.24 [0.47; 3.29] | | Barzizza (ASA), 1993 | aspirin vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| WASH (aspirin), 2004 | aspirin 300 mg/day (n=91) vs. no treatment (n=99)
| patients with heart failure and left ventricular systolic dysfunction requiring diuretic therapy with LVEF<=35%
| open Sample size: 91/99 Primary endpoint: death, MI, stroke FU duration: 27 months
| | Barzizza (ASA), 1993 | aspirin 300mg (n=26) vs. placebo (n=23) ASA 300mg (n=26) vs ASA 300mg + Dipy 200mg (n=25) vs warfarin INR 2-3 (n=24) vs placebo (n=23) | patients with dilated cardiomyopathy and evidence of intraventricular thrombi | NA Parallel groups Sample size: 26/23 Primary endpoint: intraventricular thrombi resolution FU duration: 6 months |
|
| antithrombotics | enoxaparin | versus UFH No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| THE-PRINCE (Kleber), 2003 | enoxaparin vs UFH | | | |
| Trial | Treatments | Patients | Method |
|---|
| THE-PRINCE (Kleber), 2003 | enoxaparin 40mg once daily for 10+/-2 days (n=164) vs. UFH 5000 IU 3 times daily for 10+/-2 days (n=169) | patients hospitalized for severe respiratory disease or heart failure (NYHA III, IV) Patients
were stratified and enrolled according to their underlying disease: severe respiratory disease or heart failure | open Parallel groups Sample size: 164/169 Primary endpoint: thromboembolic event FU duration: |
|
| antithrombotics | rivaroxaban | versus No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| COMMANDER HF, 2018 | rivaroxaban vs placebo | | | death 0.98 [0.87; 1.10] |
| Trial | Treatments | Patients | Method |
|---|
| COMMANDER HF, 2018 | rivaroxaban at a dose of 2.5 mg twice daily (n=2507) vs. placebo (n=2515) | patients who had chronic heart failure, a left ventricular ejection fraction of 40% or less, coronary artery disease, and elevated plasma concentrations of natriuretic peptides and who did not have atrial fibrillation | Sample size: 2507/2515 Primary endpoint: death all cause, MI, stroke FU duration: 21.1 months |
|
| antithrombotics | warfarin | versus placebo or no treatment No demonstrated result for efficacy | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| WASH (warfarin), 2004 | warfarin vs no treatment | | | death 1.17 [0.69; 1.97] bleeding ∞ [NaN; ∞] stroke (fatal and non fatal) 0.00 [0.00; NaN] MI (fatal or non fatal) 0.48 [0.13; 1.79] All-cause hospitalisation 0.97 [0.72; 1.31] | | HELAS (warfarin vs placebo), 2006 | warfarin vs placebo | | | | | Barzizza (warfarin), 1993 | warfarin vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| WASH (warfarin), 2004 | warfarin (target INR 2.5) (n=89) vs. no treatment (n=99) | patients with heart failure and left ventricular systolic dysfunction requiring diuretic therapy with LVEF<=35% | open Parallel groups Sample size: 89/99 Primary endpoint: death, MI, stroke FU duration: 27 months | | HELAS (warfarin vs placebo), 2006 | warfarin (target
INR of 2–3) (n=38) vs. placebo (n=44) | HF due to dilated cardiomyopathy | double blind Parallel groups Sample size: 38/44 Primary endpoint: stroke, PE, MI, hospitalization, death FU duration: 21.9 months | | Barzizza (warfarin), 1993 | warfarin to maintain INR between 2 and 3 (n=24) vs. placebo
(n=23) ASA 300mg (n=26) vs ASA 300mg + Dipy 200mg (n=25) vs warfarin INR 2-3 (n=24) vs placebo (n=23)
| patients with dilated cardiomyopathy and evidence of intraventricular thrombi
| NA Sample size: 24/23 Primary endpoint: intraventricular thrombi resolution FU duration: 6 months
|
|
| antithrombotics | warfarin | versus antiplatelet drugs No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| HELAS (warfarin vs aspirin), 2006 | warfarin vs aspirin | | | | | WATCH (warfarin vs aspirin), 2009 | warfarin vs aspirin | Ischemic stroke 0.24 [0.07; 0.85] | | death 0.95 [0.73; 1.23] bleeding 1.43 [0.81; 2.52] stroke (fatal and non fatal) 0.58 [0.26; 1.32] |
| Trial | Treatments | Patients | Method |
|---|
| HELAS (warfarin vs aspirin), 2006 | warfarin (n=54) vs. aspirin 325mg/d (n=61) | HF related to ischemic heart disease with LVFE<35% | Double blind Parallel groups Sample size: 54/61 Primary endpoint: stroke, PE, ME, hospitalisation, death FU duration: 21.9 months | | WATCH (warfarin vs aspirin), 2009 | warfarin (target INR 2.5-3.0) (n=540) vs. aspirin 162 mg daily (n=523) | symptomatic heart failure patients in sinus rhythm with ejection fractions 35% taking angiotensin-converting enzyme inhibitors (unless not tolerated) and diuretics | open Parallel groups Sample size: 540/523 Primary endpoint: death from all causes, nonfatal FU duration: |
|
| beta-blockers | bisoprolol | versus placebo or control No demonstrated result for efficacy | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| CIBIS, 1994 | bisoprolol vs placebo | cardiovascular death 0.68 [0.47; 0.98] death or HF hospitalisation 0.77 [0.61; 0.97] hospitalisation for heart failure 0.66 [0.49; 0.90] NYHA improvement 1.42 [1.02; 1.99] | | NYHA deterioration 1.18 [0.77; 1.79] all cause death 0.79 [0.57; 1.10] | | CIBIS II, 1999 | bisoprolol vs placebo | all cause death 0.68 [0.56; 0.82] death or HF hospitalisation 0.83 [0.75; 0.93] Sudden death 0.58 [0.41; 0.81] | | | | CIBIS II (elderly subgroup), 1999 | Bisoprolol vs placebo | All cause death 0.70 [0.50; 0.98] | | |
| Trial | Treatments | Patients | Method |
|---|
| CIBIS, 1994 | bisoprolol 5mg/d (n=320) vs. placebo (n=321) | stable chronic idiopathic dilated cardiomyopathy heart failure NYHA 3-4, EF<40% | Double blind Parallel groups Sample size: 320/321 Primary endpoint: Mortality FU duration: 1.9 years (range 4-44 mo) | | CIBIS II, 1999 | Bisoprolol target dose 10mg/daily (n=1327) vs. control (n=1320) | chronic herat failure, ejection fraction<=35%, NYHA 3-4 | Double blind Parallel groups Sample size: 1327/1320 Primary endpoint: all-cause mortality FU duration: 1.3 years Trial stop eraly but with a planned follox-up of 24 months | | CIBIS II (elderly subgroup), 1999 | Bisoprolol (n=539) vs. placebo (n=0) | Patients aged 71 years and older | Sample size: 539/0 Primary endpoint: FU duration: |
|
| beta-blockers | bucindolol | versus placebo or control No demonstrated result for efficacy | 5 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| BEST, 2001 | bucindolol vs placebo | cardiovascular death 0.88 [0.78; 1.00] hospitalisation for heart failure 0.84 [0.76; 0.92] | | all cause death 0.92 [0.82; 1.02] | | Pollock, 1990 | Bucindolol vs placebo | | | | | Woodley, 1991 | Bucindolol vs placebo | | | | | Bristow, 1994 | Bucindolol vs placebo | | | | | MERIT-HF (elderly subgroup), 1999 | Bucindolol vs placebo | All cause death 0.70 [0.53; 0.92] | | |
| Trial | Treatments | Patients | Method |
|---|
| BEST, 2001 | bucindolol titrated to 50mg txice daily (n=1354) vs. placebo (n=1354) | patients with heart failure NYHA class III or IV and a left ventricular ejection fraction of 35 percent or lower | Double blind Parallel groups Sample size: 1354/1354 Primary endpoint: all-cause mortality FU duration: 2 years | | Pollock, 1990 | bucindolol target dose 100mg twice daily (n=12) vs. placebo (n=7) | Patienst with stable, chronic heart failure with a dilated cardiomyopathy due to ischemic or isopathic causes | Double blind Parallel groups Sample size: 12/7 Primary endpoint: Exercise tolerance, hemodynamics FU duration: 3 months | | Woodley, 1991 | bucindolol (n=29) vs. placebo (n=29) | NYHA 2-3, IDC/CAD | Sample size: 29/29 Primary endpoint: Exercise tolerance, hemodynamics FU duration: 3 mo | | Bristow, 1994 | bucindolol (n=105) vs. placebo (n=34) | NYHA 2-3, IDC | Sample size: 105/34 Primary endpoint: Functional class FU duration: 3 mo | | MERIT-HF (elderly subgroup), 1999 | Bucindolol (n=1330) vs. placebo (n=0) | Patients aged 65 years and olderwith chronic heart failure in NYHA functional class II-IV and with ejection fraction of 0.40 or less, stabilised with optimum standard therapy | Sample size: 1330/0 Primary endpoint: FU duration: |
|
| beta-blockers | carvedilol | versus placebo or control No demonstrated result for efficacy | 12 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ANZ-HeFT, 1997 | carvedilol vs placebo | | | NYHA deterioration 1.23 [0.77; 1.97] all cause death 0.77 [0.45; 1.34] cardiovascular death 0.90 [0.49; 1.66] death or HF hospitalisation 0.72 [0.49; 1.06] hospitalisation for heart failure 0.70 [0.43; 1.15] NYHA improvement 0.94 [0.68; 1.28] | | COPERNICUS, 2002 | carvedilol vs placebo | all cause death 0.67 [0.54; 0.83] death or HF hospitalisation 0.82 [0.74; 0.91] hospitalisation for heart failure 0.67 [0.59; 0.76] | | | | CAPRICORN, 2001 | carvedilol vs placebo | all cause death 0.78 [0.62; 0.97] cardiovascular death 0.76 [0.60; 0.96] | | death or HF hospitalisation 0.93 [0.83; 1.05] hospitalisation for heart failure 0.86 [0.69; 1.09] | | Metra, 1994 | carvedilol vs placebo | | | | | Olsen, 1995 | carvedilol vs placebo | | | | | Krum, 1995 | carvedilol vs placebo | | | | | Bristow (MOCHA), 1996 | carvedilol vs placebo | | | | | Parker, 1996 | carvedilol vs placebo | | | cardiovascular death 0.70 [0.42; 1.17] Sudden death 0.87 [0.42; 1.79] | | Colucci, 1996 | carvedilol vs placebo | | | | | Cohn, 1997 | carvedilol vs placebo | | | | | Carvedilol U.S. Trials (elderly subgroup), 1996 | Carvedilol vs placebo | All cause death 0.45 [0.23; 0.86] | | | | COPERNICUS (elderly subgroup), 2001 | Carvedilol vs placebo | All cause death 0.75 [0.57; 0.99] | | |
| Trial | Treatments | Patients | Method |
|---|
| ANZ-HeFT, 1997 | carvedilol target dose 25mg twice daily (n=207) vs. placebo (n=208) | chronic stable heart failure, NYHA 1-3 | Double blind Parallel groups Sample size: 207/208 Primary endpoint: Exercise tolerance, EF Morbidity 1 mortality FU duration: 19 mo (range 18-24 mo) | | COPERNICUS, 2002 | carvedilol traget dose of 25 mg twice daily (n=1156) vs. placebo (n=1133) | patients with symptoms of heart failure at rest or on minimal exertion and with an ejection fraction <25% (but not volume-overloaded) | Double blind Parallel groups Sample size: 1156/1133 Primary endpoint: all-cause mortality FU duration: 10.4 months | | CAPRICORN, 2001 | carvedilol target dose 25mg twice daily (n=975) vs. placebo (n=984) | proven acute myocardial infarction and a left-ventricular ejection fraction of <=40% | Double blind Parallel groups Sample size: 975/984 Primary endpoint: all-cause death or hospitalization FU duration: 1.3 years | | Metra, 1994 | carvedilol (n=20) vs. placebo (n=20) | NYHA 2-3, IDC | Sample size: 20/20 Primary endpoint: Hemodynamics FU duration: 4 mo | | Olsen, 1995 | carvedilol (n=36) vs. placebo (n=23) | NYHA 2-4, IDC/CAD | Sample size: 36/23 Primary endpoint: Hemodynamics FU duration: 4 mo | | Krum, 1995 | carvedilol 25 mg twice daily during 14 weeks (n=33) vs. placebo (n=16) selection of patients tolerating during run-in period 12.5mg twice daily | Patients with advanced heart failure(NYHA 3-4), EF <=0.35 | Sample size: 33/16 Primary endpoint: Hemodynamics FU duration: 3.5 mo | | Bristow (MOCHA), 1996 | carvedilol (n=261) vs. placebo (n=84) | NYHA 2-4, IDC/CAD | Double blind Parallel groups Sample size: 261/84 Primary endpoint: Exercise tolerance FU duration: 6.5-8 mo | | Parker, 1996 | carvediloltarget dose 25 mg twice daily (n=696) vs. placebo (n=398) nested dose-ranging protocol (6.25, 12.5, 25 mg twice daily) cocnerning 345 patients (32%) | patients with heart failure and ejection fraction<0.35 | Double blind Parallel groups Sample size: 696/398 Primary endpoint: Exercise tolerance FU duration: 6.5 mo (1 day - 15.1 mo) | | Colucci, 1996 | carvedilol (n=232) vs. placebo (n=134) | mild symptomatic heart failure; ejection fraction<=0.35; 6-minute walk test of 450-550m; on optimal standard therapy including ACE inhibitors | Double blind Parallel groups Sample size: 232/134 Primary endpoint: progression of heart failure FU duration: 213 days (0.6 years) | | Cohn, 1997 | carvedilol (n=70) vs. placebo (n=35) | NYHA 3-4, IDC/CAD | Sample size: 70/35 Primary endpoint: Quality of life FU duration: <8 mo | | Carvedilol U.S. Trials (elderly subgroup), 1996 | Carvedilol (n=554) vs. placebo (n=0) | Patients aged 65 years and older | Sample size: 554/0 Primary endpoint: FU duration: | | COPERNICUS (elderly subgroup), 2001 | Carvedilol (n=1102) vs. placebo (n=0) | Patients aged 59 years and older | Sample size: 1102/0 Primary endpoint: FU duration: |
|
| beta-blockers | carvedilol | versus No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| CARMEN (carvedilol alone), 2004 | carvedilol vs enalapril | | | all cause death 0.99 [0.49; 2.03] cardiovascular death 0.92 [0.45; 1.91] hospitalisation for heart failure 0.75 [0.36; 1.53] |
| Trial | Treatments | Patients | Method |
|---|
| CARMEN (carvedilol alone), 2004 | carvedilol (target 25 mg bid) (n=191) vs. enalapril (target 10 mg bid) (n=190) | patients with mild heart failure | ND Sample size: 191/190 Primary endpoint: left ventricular remodelling FU duration: 18 months |
|
| beta-blockers | carvedilol | versus beta-blockers No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| COMET, 2003 | carvedilol vs metoprolol | all cause death 0.86 [0.78; 0.94] cardiovascular death 0.82 [0.74; 0.91] | | death or HF hospitalisation 0.97 [0.93; 1.01] |
| Trial | Treatments | Patients | Method |
|---|
| COMET, 2003 | carvedilol (target dose 25 mg twice daily) (n=1511) vs. metoprolol tartrate target dose 50 mg twice daily (n=1518) | chronic heart failure (NYHA II–IV) with a previous admission for a cardiovascular reason and ejection fraction of less than 0·35, and have been treated optimally with diuretics and angiotensinconverting enzyme inhibitors unless not tolerated. | Double blind Parallel groups Sample size: 1511/1518 Primary endpoint: all-cause mortality and the composite endpoint FU duration: 4.83 years |
|
| beta-blockers | metoprolol | versus placebo or control No demonstrated result for efficacy | 7 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| MDC (Waagstein), 1993 | metoprolol vs placebo | | | NYHA deterioration 0.87 [0.34; 2.20] all cause death 1.07 [0.61; 1.86] death or HF hospitalisation 0.77 [0.56; 1.06] hospitalisation for heart failure 0.74 [0.50; 1.07] NYHA improvement 1.26 [0.93; 1.70] | | MERIT-HF, 1999 | metoprolol vs placebo | all cause death 0.67 [0.55; 0.82] cardiovascular death 0.63 [0.51; 0.78] Sudden death 0.60 [0.46; 0.79] | | | | Engelmeier, 1985 | metoprolol vs placebo | | | | | Fisher, 1994 | metoprolol vs placebo | | | | | Eichhorn, 1994 | metoprolol vs placebo | | | | | RESOLVD, 2000 | metoprolol vs placebo | | | | | BEST (elderly subgroup), 2001 | Metoprolol vs placebo | | | All cause death 0.91 [0.75; 1.11] |
| Trial | Treatments | Patients | Method |
|---|
| MDC (Waagstein), 1993 | metoprolol target dose 100-150 mg daily (dose divided into two or three per day) (n=194) vs. placebo (n=189) | patient with heart failure due to idiopathic dilated cardiomyopathy (NYHA 1-3) and EF<40% | Double blind Parallel groups Sample size: 194/189 Primary endpoint: death or transplantation waiting list FU duration: 18 months | | MERIT-HF, 1999 | metoprolol CR/XL at target dose of 200 mg once daily (n=1990) vs. placebo (n=2001) | patients with chronic heart
failure in New York Heart Association (NYHA) functional class II–IV and with ejection fraction of 0·40 or less, stabilised with optimum standard therapy | Double blind Parallel groups Sample size: 1990/2001 Primary endpoint: all-cause death FU duration: 1 y | | Engelmeier, 1985 | metoprolol (n=9) vs. placebo (n=16) | NYHA 2-4, IDC | Sample size: 9/16 Primary endpoint: Exercise tolerance FU duration: 12 mo | | Fisher, 1994 | metoprolol (n=25) vs. placebo (n=25) | NYHA 3-4, CAD | Sample size: 25/25 Primary endpoint: Exercise tolerance FU duration: 6 mo | | Eichhorn, 1994 | metoprolol (n=15) vs. placebo (n=9) | NYHA 2-3, IDC | Sample size: 15/9 Primary endpoint: Hemodynamics FU duration: 3 mo | | RESOLVD, 2000 | metoprolol CR 200 mg/d (n=214) vs. placebo (n=212) | CHF of mixed causes, patients with symptomatic CHF(NYHA II to IV), a 6-minute walk distance of <500 m, and an LV ejection fraction (EF) of<40% | Double aveugle Parallel groups Sample size: 214/212 Primary endpoint: FU duration: 6 mo | | BEST (elderly subgroup), 2001 | Metoprolol (n=1092) vs. placebo (n=0) | Upper tertile age | Sample size: 1092/0 Primary endpoint: FU duration: |
|
| beta-blockers | nebivolol | versus placebo or control No demonstrated result for efficacy | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Lechat, 1991 | Nebivolol vs placebo | | | | | Wisenbaugh, 1993 | Nebivolol vs placebo | | | all cause death ∞ [NaN; ∞] hospitalisation for heart failure NaN [NaN; NaN] | | nebivolol vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Lechat, 1991 | nebivolol 5mg/d (n=6) vs. placebo (n=6) | NYHA 3-4 | Double aveugle Parallel groups Sample size: 6/6 Primary endpoint: Exercise tolerance FU duration: 1.5 month | | Wisenbaugh, 1993 | nebivolol (n=11) vs. placebo (n=13) | patients with dilated idiopathic or ischemic cardiomyopathy (ejection fraction 0.15 to 0.40) in stable NYHA class II or III | double blind Parallel groups Sample size: 11/13 Primary endpoint: Hemodynamics MSI FU duration: 3 mo | | SENIORS, 2005 | nebivolol (titrated from 1.25 mg once
daily to 10 mg once daily) (n=1067) vs. placebo (n=1061) | patients aged 70 years with a
history of heart failure (hospital admission for heart failure within the previous year
or known ejection fraction 35%), | Double blind Parallel groups Sample size: 1067/1061 Primary endpoint: FU duration: 21 months |
|
| calcium channel blockers | amlodipine | versus placebo or no treatment No demonstrated result for efficacy | 7 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| PRAISE, 1996 | amlodipine vs placebo | | | all-cause death 0.87 [0.74; 1.01] cardiovascular event 0.92 [0.80; 1.06] | | PRAISE II , 2000 | Amlodipine vs placebo | | | all-cause death 1.06 [0.92; 1.22] | | amlodipine vs control | | | | | Smith, 1994 | amlodipine vs control | | | | | amlodipine vs control | | | | | amlodipine vs control | | | | | amlodipine vs control | | | |
| Trial | Treatments | Patients | Method |
|---|
| PRAISE, 1996 | amlodipine 10 mg once daily (n=571) vs. placebo (n=582) | patients with severe chronic heart failure and ejection fractions of less than 30 percent appl | Double blind Parallel groups Sample size: 571/582 Primary endpoint: death from any cause and hospitalization FU duration: median 13.8 mo (range 6-33 mo) | | PRAISE II , 2000 | Amlodipine (n=826) vs. placebo (n=826) | heart failure in non ischemic cardiomyopathy | Sample size: 826/826 Primary endpoint: FU duration: up to 4 years | | Packer, 1991 | amlodipine (n=-9) vs. (n=-9) | CHD multiple cause, NYHA class II-III | Double blind Sample size: -9/-9 Primary endpoint: FU duration: 2 months | | Smith, 1994 | amlodipine (n=-9) vs. (n=-9) | CHD multiple cause, NYHA class II-III | Double blind Sample size: -9/-9 Primary endpoint: FU duration: 3 months | | Udelson, 1996 | amlodipine (n=-9) vs. (n=-9) | patients with congestive heart failure due to ischaemic heart disease, NYHA class II-III | Double blind Sample size: -9/-9 Primary endpoint: FU duration: 3 months | | Binkley, 1996 | amlodipine (n=-9) vs. (n=-9) | CHD multiple cause, NYHA class II-III | Double blind Sample size: -9/-9 Primary endpoint: FU duration: 3 months | | Ghali, 1997 | amlodipine (n=-9) vs. (n=-9) | CHD multiple cause, NYHA class III-IV | Double blind Sample size: -9/-9 Primary endpoint: FU duration: 3 months |
|
| calcium channel blockers | diltiazem | versus placebo or no treatment No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Liao , 1998 | Diltiazem vs placebo | all-cause death 0.31 [0.10; 0.94] hospitalization for heart failure 0.26 [0.14; 0.46] | | | | DiDi, 1996 | diltiazem vs placebo | | | all-cause death 1.02 [0.37; 2.80] |
| Trial | Treatments | Patients | Method |
|---|
| Liao , 1998 | diltiazem 30mg twice daily (n=114) vs. control (vitamin B1 30mg twice daily) (n=107) | patients with dilated cardiomyopathy | Simple aveugle Parallel groups Sample size: 114/107 Primary endpoint: ventricular function FU duration: 6 months | | DiDi, 1996 | diltiazem 60mg three times daily (n=92) vs. placebo (n=94) | idiopathic dilated cardiomyopathy and LVEF<0.50 | Double blind Parallel groups Sample size: 92/94 Primary endpoint: mortality and transplant listing FU duration: 24 months |
|
| calcium channel blockers | felodipine | versus placebo or no treatment No demonstrated result for efficacy | 4 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| VHeFT III, 1997 | felodipine vs placebo | | | all-cause death 1.08 [0.67; 1.73] | | Kassis, 1987 | felodipine vs placebo | | | | | Littler, 1995 | Felodipine vs placebo | | | all-cause death 1.35 [0.23; 7.95] | | felodipine vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| VHeFT III, 1997 | felodipine 5mg twice daily (n=224) vs. placebo (n=226) | male patient over 18 years with heart failure | Double blind Parallel groups Sample size: 224/226 Primary endpoint: exercise tolerance FU duration: mean 18mo (range 3-39 mo) | | Kassis, 1987 | felodipine 10 mg twice daily (n=18) vs. placebo (n=18) | patients on conventional therapy for severe CHF | Double blind Cross over Sample size: 18/18 Primary endpoint: haemodynamic FU duration: 3 weeks | | Littler, 1995 | felodipine extended release 2.5-10mg twice daily (in addition to existing background medication) for 12 weeks (n=132) vs. placebo (n=119) | patients with NYHA class II-III stable congestive heart failure despite treatment with ACE inhibitors, diuretic and digoxin or any combinaison of these drugs | Double blind Parallel groups Sample size: 132/119 Primary endpoint: exercise tolerance FU duration: 3 months | | Kassis, 1990 | felopidine 10 mg BID (n=10) vs. placebo (n=10) | severe congestive heart failure (NYHA class III) | Double blind Parallel groups Sample size: 10/10 Primary endpoint: haemodynamic FU duration: 6 months |
|
| calcium channel blockers | felodipine | versus angiotensin-converting enzyme inhibitors No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| felodipine vs enalapril | | | | | felodipine vs enalapril | | | |
| Trial | Treatments | Patients | Method |
|---|
| Dunselman, 1990 | felodipine 10 mg b.i.d. (n=9) vs. enalapril 10 mg b.i.d. (n=11) | patients with congestive heart failure due to ischaemic heart disease and NYHA class III | Double blind Sample size: 9/11 Primary endpoint: cardiopulmonary exercise tests FU duration: 4 months | | De Vries, 1995 | felodipine 2.5mg twice daily (n=22) vs. enalapril 2.5mg twice daily (n=24) | patients NYHA class II-III with left ventricular ejection fraction <0.4, symptoms of CHD despite therapy with diuretics and digoxin | Double blind Parallel groups Sample size: 22/24 Primary endpoint: cardiopulmonary exercise tests FU duration: 4 months |
|
| calcium channel blockers | isradipine | versus placebo or no treatment No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| isradipine vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Van den Toren, 1996 | isradipine up to 5mg 3 times daily (n=19) vs. placebo (n=0) | patients with congestive heart failure due to ischaemic heart disease, NYHA class II-III, FE<40% | Double blind Parallel groups Sample size: 19/0 Primary endpoint: Hemodynamic FU duration: 3 months |
|
| calcium channel blockers | mibefradil | versus placebo or no treatment No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| MACH 1, 2000 | mibefradil vs placebo | hospitalization for heart failure 0.85 [0.75; 0.97] | | all-cause death 1.10 [0.96; 1.25] cardiovascular death 1.08 [0.94; 1.24] |
| Trial | Treatments | Patients | Method |
|---|
| MACH 1, 2000 | mibefradil titrated up to100mg daily (n=1295) vs. placebo (n=1295) | Patients with moderate to severe congestive heart failure (NYHA class II to IV and left ventricular fraction ,35%).pj | Double aveugle Parallel groups Sample size: 1295/1295 Primary endpoint: all-cause mortality FU duration: 1.6 years |
|
| calcium channel blockers | nicardipine | versus placebo or no treatment No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| nicardipine vs control | | | | | nicardipine vs control | | | |
| Trial | Treatments | Patients | Method |
|---|
| Gheorghiade, 1991 | nicardipine (n=-9) vs. (n=-9) | CHD multiple cause, NYHA class III | Double blind Sample size: -9/-9 Primary endpoint: FU duration: 4 months | | Abrams, 1993 | nicardipine (n=-9) vs. (n=-9) | CHD multiple cause, NYHA class III-IV | Double blind Sample size: -9/-9 Primary endpoint: FU duration: 4 months |
|
| calcium channel blockers | nisoldipine | versus placebo or no treatment No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Nisoldipine vs placebo | | | | | nisoldipine vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Gaudron, 1996 | Nisoldipine (n=-9) vs. placebo (n=-9) | patients with congestive heart failure due to ischaemic heart disease, NYHA class II, FE<=45% | Sample size: -9/-9 Primary endpoint: FU duration: 18 months | | Rousseau, 1994 | nisoldipine 20 mg once daily (n=16) vs. placebo (n=16) | patients with congestive heart failure due to ischaemic heart disease, NYHA class II | Double blind Sample size: 16/16 Primary endpoint: myocardial perfusion and neuro-hormonal status FU duration: 2 months |
|
| calcium channel blockers | nisoldipine | versus angiotensin-converting enzyme inhibitors No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| nisoldipine vs captopril | | | |
| Trial | Treatments | Patients | Method |
|---|
| Schofer, 1990 | nisoldipine (2 X 10 mg) (n=24) vs. captopril (3 X 25 mg) (n=0) | patients with congestive heart failure due to ischaemic heart disease, NYHA class II-III | Double blind Sample size: 24/0 Primary endpoint: haemodynamic response FU duration: 3 months |
|
| cholesterol lowering intervention | atorvastatin | versus placebo or control No demonstrated result for efficacy | 4 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Strey, 2005 | atorvastatin vs placebo | | | | | Wojnicz, 2006 | atorvastatin vs control | | | hospitalization for heart failure 0.00 [0.00; NaN] All cause death NaN [NaN; NaN] cardiovascular death NaN [NaN; NaN] | | Sola, 2006 | atorvastatin vs placebo | | | hospitalization for heart failure 0.58 [0.26; 1.25] All cause death 1.00 [0.26; 3.79] | | Yamada, 2007 | atorvastatin vs control | | | hospitalization for heart failure 0.33 [0.08; 1.45] All cause death 0.00 [0.00; NaN] cardiovascular death 0.00 [0.00; NaN] |
| Trial | Treatments | Patients | Method |
|---|
| Strey, 2005 | atorvastatin 40mg (n=24) vs. placebo (n=24) | patients with stable, symptomatic heart failure (New York Heart Association Class II or III) and a left ventricular ejection fraction <40% | Cross over Sample size: 24/24 Primary endpoint: FU duration: 6 weeks | | Wojnicz, 2006 | atorvastatin 40 mg/day (n=36) vs. conventional treatment for heart
failure (n=38) | patients with inflammatory dilated cardiomyopathy (DC) (positive immunohistochemistry results on endomyocardial biopsy) | open Parallel groups Sample size: 36/38 Primary endpoint: FU duration: 6 months | | Sola, 2006 | atorvastatin 20 mg/day (n=54) vs. placebo (n=54) | patients with nonischemic HF and a left ventricular ejection fraction (LVEF) <=35% | double blind Parallel groups Sample size: 54/54 Primary endpoint: FU duration: 1y | | Yamada, 2007 | atorvastatin 10 mg/d (n=19) vs. standard treatment (n=19) | outpatients with mild to moderate CHF and radionuclide left ventricular ejection fraction
(LVEF) <40% | Parallel groups Sample size: 19/19 Primary endpoint: FU duration: mean 2.58y |
|
| cholesterol lowering intervention | cerivastatin | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Laufs, 2004 | cerivastatin vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Laufs, 2004 | cerivastatin 0.4 mg (n=8) vs. placebo (n=7) | patients with heart failure NYHA
II-III caused by non-ischemic dilated
cardiomyopathy | double blind Parallel groups Sample size: 8/7 Primary endpoint: FU duration: mean 20 weeks |
|
| cholesterol lowering intervention | rosuvastatin | versus placebo or control No demonstrated result for efficacy rosuvastatin inferior to placebo in terms of death or hospitalization for HF in GISSI-HF rosuvastatine, 2008 (heart failure patients) | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| CORONA, 2007 | rosuvastatin vs placebo | | | hospitalization for heart failure 0.92 [0.84; 1.01] All cause death 0.95 [0.87; 1.04] coronary event 0.94 [0.85; 1.04] cardiovascular death 1.00 [0.89; 1.11] fatal MI 1.66 [0.73; 3.78] fatal stroke 1.09 [0.67; 1.75] non fatal stroke 0.85 [0.64; 1.12] non fatal MI 0.81 [0.64; 1.03] death from noncardiovascular cause 0.86 [0.69; 1.08] cardiovascular events (fatal and non fatal) 0.94 [0.86; 1.03] incident diabetes 1.13 [0.86; 1.49] | | Krum, 2007 | rosuvastatin vs placebo | | | All cause death 0.77 [0.13; 4.36] | | GISSI-HF rosuvastatine, 2008 | rosuvastatin vs placebo | | death or hospitalization for HF 1.01 [1.01; 1.01] | hospitalization for heart failure 0.99 [0.90; 1.09] All cause death 1.02 [0.93; 1.12] coronary event 0.87 [0.62; 1.22] cardiovascular death 0.98 [0.88; 1.10] fatal MI 0.67 [0.30; 1.48] fatal stroke 1.31 [0.81; 2.12] death from noncardiovascular cause 1.20 [0.96; 1.51] fatal and non fatal stroke 1.24 [0.90; 1.71] fatal and non fatal MI 0.87 [0.62; 1.22] cardiovascular events (fatal and non fatal) 0.98 [0.92; 1.04] incident diabetes 1.08 [0.91; 1.29] |
| Trial | Treatments | Patients | Method |
|---|
| CORONA, 2007 | rosuvastatin 10mg/d (n=2514) vs. placebo (n=2497) | patients at least 60 years of age with NYHA class II, III, or IV ischemic, systolic heart failure | double blind Parallel groups Sample size: 2514/2497 Primary endpoint: cardiovascular death, MI, stroke FU duration: 32.9 months median | | Krum, 2007 | rosuvastatine 40mg/d (n=40) vs. placebo (n=46) | patients with systolic (LVEF<40%) CHF of ischemic or
nonischemic etiology | double blind Parallel groups Sample size: 40/46 Primary endpoint: LVEF by radionuclide ventriculogram FU duration: 6 months | | GISSI-HF rosuvastatine, 2008 | low-dose rosuvastatin 10 mg daily (n=2314) vs. placebo (n=2317) | Patients with NYHA classes II to IV heart failure, whatever the cause and the LVEF
and already receiving optimized recommended therapy with no clear indication or contraindication to cholesterollowering therapy | double blind Parallel groups Sample size: 2314/2317 Primary endpoint: death and death+hospitalization FU duration: 3.9y median (IQR 3-4.4) |
|
| cholesterol lowering intervention | simvastatin | versus placebo or control No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Node, 2003 | simvastatin vs placebo | | | hospitalization for heart failure 1.13 [0.07; 17.02] All cause death NaN [NaN; NaN] cardiovascular death NaN [NaN; NaN] | | Hong, 2005 | simvastatin vs control | | | cardiovascular death 0.26 [0.05; 1.20] non fatal MI 0.45 [0.08; 2.39] |
| Trial | Treatments | Patients | Method |
|---|
| Node, 2003 | simvastatin 10mg/d (n=24) vs. placebo (n=27) | patients with symptomatic, nonischemic, dilated cardiomyopathy | Sample size: 24/27 Primary endpoint: FU duration: | | Hong, 2005 | simvastatin (n=106) vs. no treatment (n=96) | patients with ischemic heart failure who underwent percutaneous coronary intervention (PCI) for acute myocardial infarction (left ventricular [LV] ejection fraction <40%) | open Parallel groups Sample size: 106/96 Primary endpoint: none FU duration: 1 year |
|
| cholesterol lowering intervention | simvastatin | versus ezetimibe No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Landmesser, 2005 | simvastatin vs ezetimibe | | | |
| Trial | Treatments | Patients | Method |
|---|
| Landmesser, 2005 | simvastatin 10mg/d (n=10) vs. ezetimibe 10mg/d (n=10) | patients with chronic heart failure | Sample size: 10/10 Primary endpoint: FU duration: |
|
| digitalis glycosides | digoxin | versus placebo No demonstrated result for efficacy | 13 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Fleg, 1982 | digoxin vs placebo | | | clinical deterioration NaN [NaN; NaN] | | Lee, 1982 | digoxin vs placebo | | | clinical deterioration 0.67 [0.28; 1.59] | | Taggart, 1983 | digoxin vs placebo | | | clinical deterioration 0.53 [0.11; 2.56] | | Captopril-Digoxin Multicenter Research Group (CDMRG), 1988 | digoxin vs placebo | hospitalization for worsening heart failure 0.28 [0.08; 0.99] clinical deterioration 0.28 [0.10; 0.81] | | all cause death 1.22 [0.42; 3.49] | | German and Austrian Xamoterol Study, 1988 | digoxin vs placebo | | | all cause death 0.00 [0.00; NaN] clinical deterioration 0.70 [0.20; 2.41] | | Guyatt, 1988 | digoxin vs placebo | | | clinical deterioration 0.00 [0.00; NaN] | | DiBianco, 1989 | digoxin vs placebo | clinical deterioration 0.31 [0.16; 0.61] | | all cause death 0.79 [0.17; 3.75] | | Pugh, 1989 | digoxin vs placebo | | | clinical deterioration 0.45 [0.17; 1.20] | | Blackwood, 1990 | digoxin vs placebo | | | all cause death 0.00 [0.00; NaN] clinical deterioration 0.00 [0.00; NaN] | | Radiance, 1993 | digoxin vs placebo | hospitalisation for heart failure 0.18 [0.04; 0.79] clinical deterioration 0.19 [0.07; 0.53] | | hospitalization for worsening heart failure 0.24 [0.05; 1.09] all cause death 3.28 [0.35; 30.96] | | Proved, 1993 | digoxin vs placebo | | | hospitalization for worsening heart failure 0.55 [0.15; 2.05] all cause death 0.55 [0.05; 5.82] clinical deterioration 0.61 [0.22; 1.67] | | DIMT, 1993 | digoxin vs placebo | | | all cause death 0.64 [0.11; 3.69] clinical deterioration 0.00 [0.00; NaN] | | Digitalis Investigation Group (DIG), 1997 | digoxin vs placebo | death due to worsening heart failure 0.88 [0.77; 1.00] hospitalization for worsening heart failure 0.77 [0.72; 0.83] hospitalisation for heart failure 0.77 [0.72; 0.83] hospitalisation of cardiovascular cause 0.92 [0.88; 0.96] | | non cardiovascular death 0.87 [0.71; 1.07] all cause death 0.99 [0.93; 1.06] Cardiovascular death 0.99 [0.93; 1.06] |
| Trial | Treatments | Patients | Method |
|---|
| Fleg, 1982 | digoxin titrated to serum level of 1.0 to 2.0 ng/mL (n=30) vs. placebo (n=30) | patients with chronic clinically compensated congestive heart failure and normal sinus rhythm | dobl eblind cross-over Sample size: 30/30 Primary endpoint: FU duration: 3 months | | Lee, 1982 | digoxin titrated to mean serum level of 1.15 ng/mL, mean dig dosage .435 mg/day (n=25) vs. placebo (n=25) | outpatients without atrial fibrillation | double blind cross-over Sample size: 25/25 Primary endpoint: FU duration: 53 days | | Taggart, 1983 | digoxin (mean plasma dig level 1.2 ng/mL) (n=22) vs. placebo (digoxin withdrawal) (n=22) | patients with sinus rhythm who had a previous history of frank heart failure | double blind cross-over Sample size: 22/22 Primary endpoint: FU duration: 3 months | | Captopril-Digoxin Multicenter Research Group (CDMRG), 1988 | digoxin of .125-.375 mg/day titrated to serum levels of .7-2.5 ng/mL (n=-9) vs. placebo (digoxin withdrawal) (n=-9) | patients with mild to moderate heart failure. | double blind parallel group Sample size: -9/-9 Primary endpoint: FU duration: 6 months | | German and Austrian Xamoterol Study, 1988 | digoxin .125 mg twice dayly (mean plasma dig level .87 ng/mL) (n=-9) vs. placebo (n=-9) | patients aged 29-80 with mild to moderate heart failure | double blind parallel group Sample size: -9/-9 Primary endpoint: FU duration: 3 months | | Guyatt, 1988 | digoxin titrated to serum level of 1.54– 2.56 nmol/L (1.2–2.0 ng/mL), mean dig dosage 0.391 mg/day (n=20) vs. placebo (n=20) | congestive heart failure patients in sinus rhythm | double blind cross-over Sample size: 20/20 Primary endpoint: FU duration: 7 weeks | | DiBianco, 1989 | digoxin .125-.5 mg/ day (n=-9) vs. placebo (n=-9) | patients in sinus rhythm with moderately severe heart failure | double blind parallel group Sample size: -9/-9 Primary endpoint: FU duration: 3 months | | Pugh, 1989 | digoxin (patient’s “usual dose” ) (n=44) vs. placebo (digoxin withdrawal) (n=44) | patients with stable heart failure in sinus rhythm and plasma digoxin concentrations over 0.8 ng/ml | double blind cross-over Sample size: 44/44 Primary endpoint: FU duration: 2 months | | Blackwood, 1990 | digoxin .25 mg/day (n=61) vs. placebo (n=0) | patients with heart failure | double blind parallel group Sample size: 61/0 Primary endpoint: FU duration: 3 months | | Radiance, 1993 | digoxin titrated to serum level of 1.2 ng/mL (mean dig dosage .38 mg/day) (n=85) vs. placebo (digoxin withdrawal) (n=93) | patients with New York Heart Association class II or III heart failure and left ventricular ejection fractions of 35 percent or less in normal sinus rhythm who were clinically stable while receiving digoxin, diuretics, and an angiotensin-converting-enzyme inhibitor (captopril or enalapril) | double blind Sample size: 85/93 Primary endpoint: FU duration: 3 months | | Proved, 1993 | digoxin titrated to serum level of 1.2 ng/mL (median dig dosage .375 mg/day) (n=42) vs. placebo (digoxin withdrawal) (n=46) | patients with chronic, stable mild to moderate heart failure | double blind withdrawal trial Sample size: 42/46 Primary endpoint: FU duration: 3 months | | DIMT, 1993 | digoxin .25 mg/day (mean plasma level .94 ng/mL) (n=55) vs. placebo (n=53) | patients with mild to moderate chronic heart failure | double blind parallel group Sample size: 55/53 Primary endpoint: FU duration: 6 months | | Digitalis Investigation Group (DIG), 1997 | digoxin dosage at investigators’ discretion (median baseline dosage in main trial of .25 mg/day) (n=3397) vs. placebo (n=3403) median dose of digoxin, 0.25 mg per day | patients with left ventricular ejection fractions of 0.45 or less and normal sinus rhythm The left ventricular
ejection fraction was assessed by radionuclide left ventriculography,
left ventricular contrast angiography, or two-dimensional
echocardiography. | Double blind Parallel groups Sample size: 3397/3403 Primary endpoint: mortality FU duration: 37 mo (mean) |
|
| diuretics | amiloride | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Cheitlin, 1991 | amiloride vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Cheitlin, 1991 | amiloride (n=12) vs. placebo (n=12) | men with a history of congestive heart failure | double blind Cross over Sample size: 12/12 Primary endpoint: haemodynamic FU duration: 12 weeks |
|
| diuretics | eplerenone | versus placebo or control No demonstrated result for efficacy eplerenone inferior to placebo in terms of serious hyperkalemia (¡Ý6.0 mmol per liter) in EPHESUS, 2003 eplerenone inferior to placebo in terms of serious hyperkalemia (¡Ý6.0 mmol per liter) in EMPHASIS-HF, 2010 | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| EPHESUS, 2003 | eplerenone vs placebo | death from any cause 0.86 [0.77; 0.96] death from cardiovascular causes 0.84 [0.74; 0.95] Sudden death 0.80 [0.66; 0.98] death from cardiovascular causes or hospitalization for cardiovascular causes 0.89 [0.82; 0.96] | serious hyperkalemia (¡Ý6.0 mmol per liter) 1.43 [1.14; 1.78] | Adverse events 0.99 [0.97; 1.02] hospitalisation for cardiovascular causes 0.93 [0.84; 1.03] | | EMPHASIS-HF, 2010 | eplerenone vs placebo | death from any cause 0.81 [0.67; 0.97] death from cardiovascular causes 0.80 [0.65; 0.98] Death from any cause or hospitalization for
any reason 0.82 [0.74; 0.90] Hospitalization for heart failure 0.65 [0.54; 0.78] Hospitalization for any reason 0.84 [0.75; 0.93] Death from any cause or hospitalization for
heart failure 0.72 [0.63; 0.83] | serious hyperkalemia (¡Ý6.0 mmol per liter) 2.19 [1.58; 3.04] | Death from worsening heart failure 0.74 [0.51; 1.08] Adverse events 0.98 [0.93; 1.02] Sudden death 0.79 [0.57; 1.11] |
| Trial | Treatments | Patients | Method |
|---|
| EPHESUS, 2003 | eplerenone 25 mg per day initially, titrated to amaximum of 50 mg per day (n=3319) vs. placebo (n=3313) | patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure | Double blind Parallel groups Sample size: 3319/3313 Primary endpoint: all cause death AND cardiovascular death or hospitalization for a CV event FU duration: 16 mo (mean, range 0 to 33) | | EMPHASIS-HF, 2010 | eplerenone (n=1364) vs. placebo (n=1373) | patients with
New York Heart Association class II heart failure and an ejection fraction of no
more than 35% | double blind Parallel groups Sample size: 1364/1373 Primary endpoint: CV death, hospitalization for HF FU duration: 21 months |
|
| diuretics | furosemide | versus active treatment No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Boccanelli, 1986 | furosemide vs captopril | | | NYHA functional class improvement 0.71 [0.45; 1.14] worsening heart failure, ∞ [NaN; ∞] | | Cowley, 1986 | furosemide vs captopril | | | |
| Trial | Treatments | Patients | Method |
|---|
| Boccanelli, 1986 | furosemide 25 to 100 mg od (n=8) vs. captopril 12.5 to 50 mg bid +furosemide 25mg od (n=7) | patients with moderate congestive heart failure not completely controlled on digoxin (0.25 mg o.d.) and frusemide (25 mg o.d.), | double blind Parallel groups Sample size: 8/7 Primary endpoint: exercise FU duration: 13 weeks | | Cowley, 1986 | furosemide (increased doses of frusemide) (n=10) vs. captopril (addition) (n=10) introduction | patients with moderate heart failure who still had symptoms despite 40 mg frusemide daily | double blind Cross over Sample size: 10/10 Primary endpoint: exercise tolerance FU duration: |
|
| diuretics | hydrochlorothiazide | versus active treatment No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Nordrehaug, 1992 | hydrochlorothiazide vs benazepril | NYHA functional class improvement 0.06 [0.01; 0.41] | | | | Sievert, 1989 | hydrochlorothiazide+triamterene vs digoxin | | | |
| Trial | Treatments | Patients | Method |
|---|
| Nordrehaug, 1992 | hydrochlorothiazide 50 mg daily (n=29) vs. benazepril 20 mg daily (n=29) | patients with symptomatic (NYHA functional class 2) mild heart failure | double blind Cross over Sample size: 29/29 Primary endpoint: none FU duration: 8 weeks | | Sievert, 1989 | hydrochlorothiazide+triamterene (n=16) vs. digoxin (n=16) | patients in heart failure and sinus rhythm | double blind Cross over Sample size: 16/16 Primary endpoint: haemodynamic response FU duration: 5 weeks |
|
| diuretics | rolofylline | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| PROTECT-1 | rolofylline vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| PROTECT-1 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: |
|
| diuretics | spironolactone | versus placebo or control No demonstrated result for efficacy spironolactone inferior to placebo in terms of Discontinuation because of adverse event in RALES, 1998 spironolactone inferior to placebo in terms of NYHA functional class improvement in RALES, 1998 | 12 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| RALES, 1998 | spironolactone vs placebo | death from any cause 0.75 [0.67; 0.85] death from cardiovascular causes 0.74 [0.65; 0.85] Sudden death 0.76 [0.58; 1.00] hospitalisation for cardiovascular causes 0.79 [0.70; 0.90] worsening heart failure, 0.79 [0.71; 0.88] | Discontinuation because of adverse event 1.59 [1.08; 2.33] NYHA functional class improvement 1.24 [1.09; 1.41] | Adverse events 1.03 [0.99; 1.08] serious hyperkalemia (¡Ý6.0 mmol per liter) 2.05 [0.19; 22.52] | | Agostoni, 2005 | spironolactone vs placebo | | | | | Mottram, 2004 | spironolactone vs placebo | | | | | Macdonald, 2004 | spironolactone vs placebo | | | | | Cicoira, 2004 | spironolactone vs control | | | | | Cicoira, 2002 | spironolactone vs control | | | | | Yee, 2001 | spironolactone vs placebo | | | | | Tsutamoto, 2001 | spironolactone vs placebo | | | | | Ramires, 2000 | spironolactone vs control | | | | | Farquharson, 2000 | spironolactone vs placebo | | | | | MacFadyen, 1997 | spironolactone vs placebo | | | | | Barr, 1995 | spironolactone vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| RALES, 1998 | spironolactone (25 to 50 mg daily) (n=822) vs. placebo (n=841) | patients with severeheart failure | Open Parallel groups Sample size: 822/841 Primary endpoint: death from any cause FU duration: 24 mo | | Agostoni, 2005 | spironolactone 25mg/d (n=14) vs. placebo (n=15) | stable chronic heart failure patients with reduced influences lung diffusion (DLCO) | open Parallel groups Sample size: 14/15 Primary endpoint: FU duration: 6 months | | Mottram, 2004 | spironolactone 25 mg/d (n=30) vs. placebo (n=0) | hypertensive patients with diastolic heart failure | double blind Sample size: 30/0 Primary endpoint: myocardial function FU duration: 6 months | | Macdonald, 2004 | spironolactone 12.5-50 mg/d (n=43) vs. placebo (n=43) | patients with New York Heart Association class I-II congestive heart failure taking optimal treatment (including beta blockers) | double blind Cross over Sample size: 43/43 Primary endpoint: none FU duration: 3 months | | Cicoira, 2004 | spironolactone (n=47) vs. control (n=46) | chronic heart failure patients | open Sample size: 47/46 Primary endpoint: ACE gene insertion/deletion polymorphism FU duration: 12 months | | Cicoira, 2002 | spironolactone 12.5 to 50 mg/day (n=54) vs. control (n=52) | patients with chronic heart failure | open Parallel groups Sample size: 54/52 Primary endpoint: Ventricular Function and Exercise tolerance FU duration: 12 months | | Yee, 2001 | spironolactone 50mg/d (n=28) vs. placebo (n=28) | patients with New York Heart Association class II to IV congestive heart failure | double blind Sample size: 28/28 Primary endpoint: FU duration: 4 weeks | | Tsutamoto, 2001 | spironolactone 25 mg daily (n=20) vs. placebo (n=17) | patients with mild-to-moderate nonischemic congestive heart failure | double blind Parallel groups Sample size: 20/17 Primary endpoint: neurohumoral factors FU duration: 12 weeks | | Ramires, 2000 | spironolactone (n=19) vs. standard medical treatment (n=16) | patients with systolic dysfunction and NYHA class III CHF secondary to dilated or ischemic cardiomyopathy | open Parallel groups Sample size: 19/16 Primary endpoint: none FU duration: 20 weeks | | Farquharson, 2000 | spironolactone 50 mg/d (n=10) vs. placebo (n=10) | patients with NYHA class II to III chronic heart failure on standard diuretic/ACE inhibitor therapy | double blind Sample size: 10/10 Primary endpoint: none FU duration: 4 weeks | | MacFadyen, 1997 | spironolactone (50-100 mg/day) (n=21) vs. placebo (n=16) | patients with stable chronic heart failure | double blind Parallel groups Sample size: 21/16 Primary endpoint: none FU duration: 8 weeks | | Barr, 1995 | spironolactone 50 to 100 mg/day, titrated to blood pressure and plasma potassium (added to an angiotensin-converting enzyme inhibitor) (n=28) vs. placebo (n=14) | patients with New York Heart Association II to III congestive heart failure | double blind Parallel groups Sample size: 28/14 Primary endpoint: none FU duration: 8 weeks |
|
| diuretics | spironolactone | versus active treatment No demonstrated result for efficacy | 4 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Bednarz, 2000 | aldactone vs furosemide | | | | | Han, 1994 | spironolactone+captopril vs captopril | | | | | Mauersberger, 1985 | spironolactone+furosemide vs spironolactone+butizide | | | | | Dalhstrom, 1986 | furosemide + spironolactone vs prenalterol | | | NYHA functional class improvement 0.75 [0.41; 1.36] |
| Trial | Treatments | Patients | Method |
|---|
| Bednarz, 2000 | Aldactone 200 mg i.v (n=11) vs. furosemide 20 mg i.v (n=10) | patients with NYHA class III to IV congestive heart failure | open Sample size: 11/10 Primary endpoint: FU duration: | | Han, 1994 | captopril plus spironolactone (n=19) vs. captopril alone (n=16) | patients with refractory CHF and New York Heart Association functional class IV without renal dysfunction, hypotension and hyperkalemia | open Sample size: 19/16 Primary endpoint: none FU duration: 4 weeks | | Mauersberger, 1985 | spironolactone 50mg + furosemide 20 mg (n=22) vs. spironolactone 50mg + butizide 5mg (n=0) | patients with congestive heart failure | open Sample size: 22/0 Primary endpoint: none FU duration: | | Dalhstrom, 1986 | intensified treatment with diuretics (furosemide- spironolactone) (n=10) vs. prenalterol 100-200 mg daily in addition to their basal treatment (n=10) | patients with severe chronic congestive heart failure (CHF) due to ischaemic heart disease treated with digitalis and diuretics | double blind Cross over Sample size: 10/10 Primary endpoint: exercise tolerance FU duration: 12 weeks |
|
| Exercise Therapy | Exercise Therapy | versus placebo or control No demonstrated result for efficacy | 10 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Belardinelli et al, 1999 | Exercise training vs control | | | | | Dubach et al, 1997 | Exercise training vs control | | | | | Giannuzzi et al, 1997 | Exercise training vs control | | | | | Hambrecht et al, 1995 | Exercise training vs control | | | | | Kiilavuori et al, 2000 | Exercise training vs control | | | | | McKelvie et al, 2002 | Exercise training vs control | | | | | Zanelli et al, 1997 | Exercise training vs control | | | | | Wielenga et al, 1999 | Exercise training vs control | | | | | Willenheimer et al, 1998 | Exercise training vs control | | | | | ExTraMATCH, 2004 | Exercise training vs control | | | |
| Trial | Treatments | Patients | Method |
|---|
| Belardinelli et al, 1999 | Supervised cycling, 60 minutes three days a week for eightweeks, then two days a week (n=50) vs. no exercise (n=49) | patients with CHF | open Sample size: 50/49 Primary endpoint: FU duration: 3.1 y | | Dubach et al, 1997 | Supervised walking, two hours daily; supervised cycling 40minutes four days a week (n=24) vs. control (n=26) | patients with chronic heart failure | open Sample size: 24/26 Primary endpoint: FU duration: 0.7 y | | Giannuzzi et al, 1997 | Supervised cycling, 30 minutesthree days a week for two months, then home based 30 minutes for three days a week and walking for 30 minutes (n=46) vs. control (n=42) | patients with <40% ejection fraction after a first Q-wave myocardial infarction | open Sample size: 46/42 Primary endpoint: FU duration: 0.6 y | | Hambrecht et al, 1995 | Supervised and home based walking, calisthenics, cycling40-60 minutes a day (n=34) vs. physically inactive control group (n=35) | patients with chronic heart failure | open Sample size: 34/35 Primary endpoint: FU duration: 0.4 y | | Kiilavuori et al, 2000 | Supervised cycling 30 minutes three days a week for three months, then home basedtraining (walking, cycling,rowing, and swimming) (n=12) vs. control (n=15) | patients with stable NYHA class II-III CHF | open Sample size: 12/15 Primary endpoint: FU duration: 6.3 y | | McKelvie et al, 2002 | Supervised aerobic (cycling,treadmill, arm) and resistance training 30 minutes three days a week for three months, then home based aerobic training three days a week (n=90) vs. usual care (n=91) | patients in NYHA class I to III, with ejection fraction <40% and 6-minute walk distance <500 meters | single blind Sample size: 90/91 Primary endpoint: FU duration: 1.5 y | | Zanelli et al, 1997 | Supervised aerobic (cycling,treadmill, arm) and resistance training 30 minutes two days a week and home based cycling three days a week for two months, then only home based aerobic training five days a week (n=76) vs. (n=79) | | Sample size: 76/79 Primary endpoint: FU duration: 0.8 y | | Wielenga et al, 1999 | Supervised cycling, walking,ball game 30 minutes threedays a week for eight weeks, then two days a week (n=41) vs. control (n=39) | patients with chronic heart failure NYHA II-III | open Sample size: 41/39 Primary endpoint: FU duration: 3.9 y | | Willenheimer et al, 1998 | Supervised interval cyclingtraining (90 second exercise and 30 second rest) for 15-45 minutes two days a weekc (n=22) vs. control (n=30) | patients with stable mild-to-moderate heart failure | open Sample size: 22/30 Primary endpoint: FU duration: 4.4 y | | ExTraMATCH, 2004 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: |
|
| increasing hemoglobin concentration | taspoglutide | versus placebo or control No demonstrated result for efficacy darbepoetin alfa inferior to placebo in terms of Patient’s Global Assessment (reported improvement) in Ponikowski, 2007 | 6 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| STAMINA-HeFT (Ghali), 2008 | darbepoetin alfa vs placebo | | | Patient’s Global Assessment (reported improvement) 1.00 [0.87; 1.14] All-cause mortality 0.59 [0.29; 1.21] Adverse effect: hypertension 1.26 [0.57; 2.79] Adverse effect: stroke 0.97 [0.20; 4.73] Adverse effect: myocardial infarction 0.78 [0.21; 2.83] Adverse effect: other thromboembolic effects 1.29 [0.29; 5.68] | | van Veldhuisen, 2007 | darbepoetin alfa vs placebo | | | Patient’s Global Assessment (reported improvement) 1.33 [0.99; 1.80] All-cause mortality ∞ [NaN; ∞] Adverse effect: hypertension 0.51 [0.07; 3.52] Adverse effect: stroke NaN [NaN; NaN] Adverse effect: myocardial infarction ∞ [NaN; ∞] Adverse effect: other thromboembolic effects 0.00 [0.00; NaN] | | Ponikowski, 2007 | darbepoetin alfa vs placebo | | Patient’s Global Assessment (reported improvement) 1.93 [1.11; 3.36] | All-cause mortality 1.16 [0.08; 17.28] Adverse effect: hypertension ∞ [NaN; ∞] Adverse effect: stroke ∞ [NaN; ∞] Adverse effect: myocardial infarction 0.00 [0.00; NaN] Adverse effect: other thromboembolic effects NaN [NaN; NaN] | | Parissis, 2008 | darbepoetin alfa vs placebo | | | All-cause mortality 0.00 [0.00; NaN] Adverse effect: hypertension ∞ [NaN; ∞] Adverse effect: myocardial infarction NaN [NaN; NaN] Adverse effect: other thromboembolic effects 0.00 [0.00; NaN] | | Parissis, 2009 | darbepoetin alfa vs placebo | | | | | Kourea, 2008 | darbepoetin alfa vs placebo | | | All-cause mortality 0.32 [0.04; 2.80] Adverse effect: hypertension ∞ [NaN; ∞] Adverse effect: stroke NaN [NaN; NaN] Adverse effect: myocardial infarction 0.00 [0.00; NaN] Adverse effect: other thromboembolic effects 0.00 [0.00; NaN] |
| Trial | Treatments | Patients | Method |
|---|
| STAMINA-HeFT (Ghali), 2008 | darbepoetin alfa SC every 2 weeks for 1 year (target hemoglobin, 14.0+/-1.0 g/dL). (n=162) vs. placebo (n=157) | Patients with symptomatic HF, left ventricular ejection fraction < or = 40%, and hemoglobin > or = 9.0 g/dL and < or = 12.5 g/dL | double blind Parallel groups Sample size: 162/157 Primary endpoint: treadmill exercise time FU duration: 27 weeks | | van Veldhuisen, 2007 | darbepoetin alfa subcutaneously every 2 weeks for 26 weeks at a starting weight-adjusted dose of 0.75 mcg/kg or a fixed dose of 50 mcg (n=110) vs. placebo (n=55) | Patients with chronic heart failure (>=3 months), left ventricular ejection fraction <= 40%, and Hb 9.0 to 12.5 g/dL | double blind Parallel groups Sample size: 110/55 Primary endpoint: node defined FU duration: 27 weeks | | Ponikowski, 2007 | Subcutaneous (SC) Darbepoetin Alfa (n=19) vs. subcutaneous placebo (n=22) | patients with Symptomatic Congestive Heart Failure (CHF) and Anemia | double blind Parallel groups Sample size: 19/22 Primary endpoint: Exercise tolerance FU duration: 27 weeks | | Parissis, 2008 | 3-month darbepoetin alpha regimen at 1.5 microg/kg every 20 days plus oral iron (n=21) vs. placebo plus oral iron (n=11) | CHF patients NYHA II-III, LV ejection fraction [EF] <40%, hemoglobin level <12.5 g/dL, serum creatinine level <2.5 mg/dL | Sample size: 21/11 Primary endpoint: none defined FU duration: | | Parissis, 2009 | 3-month darbepoetin alfa regimen at 1.5 microg/kg every 20 days plus oral iron (n=30) vs. placebo plus oral iron (n=0) | patients with CHF (LV ejection fraction [LVEF] <40%, hemoglobin <12.5 g/dl, and serum creatinine <2.5 mg/dl | Sample size: 30/0 Primary endpoint: FU duration: | | Kourea, 2008 | 3-month darbepoietin-alpha at 1.5 microg/Kg every 20 days plus iron orally (n=21) vs. placebo plus iron orally (n=20) | CHF patients NYHA II-III; left ventricular ejection fraction <40%; hemoglobin<12.5 g/dl; serum creatinine<2.5 mg/dl | double blind Sample size: 21/20 Primary endpoint: FU duration: |
|
| Miscellaneous | rolofylline | versus No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| PROTECT, 2010 | rolofylline vs placebo | | | treatment success 0.92 [0.78; 1.09] |
| Trial | Treatments | Patients | Method |
|---|
| PROTECT, 2010 | daily intravenous rolofylline (30 mg) for up to 3 days (n=-9) vs. placebo (n=-9) | patients hospitalized for acute heart failure with impaired renal function | double-blind Parallel groups Sample size: -9/-9 Primary endpoint: treatment success FU duration: 3 days (60 days) |
|
| phosphodiesterase III inhibitors | amrinone | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| AMTG, 1985 | Amrinone vs placebo | | | Total mortality 1.11 [0.16; 7.55] Worsening heart failure (requiring intervention) 0.74 [0.22; 2.45] |
| Trial | Treatments | Patients | Method |
|---|
| AMTG, 1985 | Amrinone <600mg/day (n=-9) vs. placebo (n=-9) | patients with heart failure NYHA III/IV | double blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: 3 months |
|
| phosphodiesterase III inhibitors | Enoximone | versus placebo or control No demonstrated result for efficacy Enoximone inferior to placebo in terms of Total mortality in EMTG, 1990 Enoximone inferior to placebo in terms of Cardiac death in EMTG, 1990 | 7 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| WESG, 1991 | Enoximone vs placebo | | | Total mortality 1.38 [0.38; 5.01] Sudden death 1.04 [0.20; 5.49] | | EMTG, 1990 | Enoximone vs placebo | | Total mortality 3.47 [1.01; 11.87] Cardiac death 3.47 [1.01; 11.87] | Myocardial infarction (fatal & non fatal) ∞ [NaN; ∞] Sudden death ∞ [NaN; ∞] Worsening heart failure (requiring intervention) 0.91 [0.36; 2.32] Vertigo 0.52 [0.10; 2.71] | | ESG, 2000 | Enoximone vs placebo | | | Total mortality 0.25 [0.05; 1.30] Arrhythmia ∞ [NaN; ∞] | | Lardoux, 1987 | Enoximone vs placebo | | | Total mortality 0.80 [0.17; 3.81] | | ESSENTIAL (I and II), 2009 | enoximone vs placebo | | | Total mortality 0.98 [0.86; 1.12] all-cause death or HF hospitalization 0.97 [0.84; 1.12] | | Cowley, 1994 | Enoximone vs placebo | | | Total mortality 1.52 [0.92; 2.52] Cardiac death 1.46 [0.84; 2.53] | | EMOTE, 2007 | enoximone vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| WESG, 1991 | Enoximone 150, 300 mg/d (n=108) vs. placebo (n=56) | NYHA II, III | double blind Parallel groups Sample size: 108/56 Primary endpoint: Exercise tolerance FU duration: 3 months | | EMTG, 1990 | Enoximone <450 mg/d (n=50) vs. placebo (n=52) | NYHA II, III | double blind Parallel groups Sample size: 50/52 Primary endpoint: FU duration: 4 months | | ESG, 2000 | Enoximone 75-150 mg/d (n=70) vs. placebo (n=35) | NYHA II, III | double blind Parallel groups Sample size: 70/35 Primary endpoint: FU duration: 3 months | | Lardoux, 1987 | Enoximone 150, 300mg/d (n=30) vs. placebo (n=13) | NYHA NA | double blind Parallel groups Sample size: 30/13 Primary endpoint: none FU duration: 3 months | | ESSENTIAL (I and II), 2009 | enoximone titrated to 50 mg three times daily (n=926) vs. placebo (n=928) | Patients with New York Heart Association class III–IV HF symptoms, left ventricular
ejection fraction 30%, and one hospitalization or two ambulatory visits for worsening HF in the previous
year | double blind Parallel groups Sample size: 926/928 Primary endpoint: detah or CV hospitalisation FU duration: 16.6 mo (median) three co-primary endpoints: the composite of time
to all-cause mortality or cardiovascular hospitalization, analysed in the two ESSENTIAL trials combined; the
6 month change from baseline in the 6 min walk test distance (6MWTD); and the Patient Global Assessment
(PGA) at 6 months | | Cowley, 1994 | Enoximone 300mg/d (n=75) vs. placebo (n=76) | NYHA III,IV | double blind Parallel groups Sample size: 75/76 Primary endpoint: total mortality FU duration: 12 months | | EMOTE, 2007 | enoximone (n=101) vs. placebo (n=100) | patients with ultra-advanced heart failure requiring IV inotropic therapy | double blind Parallel groups Sample size: 101/100 Primary endpoint: FU duration: 26 weeks |
|
| phosphodiesterase III inhibitors | Flosequinan | versus placebo or control No demonstrated result for efficacy Flosequinan inferior to placebo in terms of Vertigo in REFLECT, 1993 | 4 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Cowley, 1993 | Flosequinan vs placebo | | | Total mortality 1.11 [0.07; 17.37] Sudden death 1.11 [0.07; 17.37] Worsening heart failure (requiring intervention) 4.44 [0.51; 38.68] | | FACET, 1993 | Flosequinan vs placebo | | | Total mortality 1.12 [0.44; 2.88] Sudden death 0.00 [0.00; NaN] Worsening heart failure (requiring intervention) 1.19 [0.59; 2.42] Arrhythmia 2.77 [0.82; 9.29] Vertigo 1.62 [0.76; 3.47] | | REFLECT, 1993 | Flosequinan vs placebo | | Vertigo 2.80 [1.04; 7.54] | Total mortality 3.76 [0.80; 17.66] Myocardial infarction (fatal & non fatal) 1.61 [0.28; 9.44] Sudden death 2.69 [0.53; 13.52] Worsening heart failure (requiring intervention) 0.51 [0.24; 1.07] Arrhythmia ∞ [NaN; ∞] | | REFLECT II, 1991 | Flosequinan vs placebo | | | Total mortality 1.11 [0.39; 3.10] |
| Trial | Treatments | Patients | Method |
|---|
| Cowley, 1993 | Flosequinan 125mg/d (n=64) vs. placebo (n=71) | NYHA II, III | double blind Parallel groups Sample size: 64/71 Primary endpoint: FU duration: 4 months | | FACET, 1993 | Flosequinan 100 and 150 mg/d (n=212) vs. placebo (n=110) | NYHA II, III | double blind Parallel groups Sample size: 212/110 Primary endpoint: FU duration: 4 months | | REFLECT, 1993 | Flosequinan 100mg/d (n=93) vs. placebo (n=100) | NYHA II,III | double blind Parallel groups Sample size: 93/100 Primary endpoint: Exercise tolerance FU duration: 3 months | | REFLECT II, 1991 | Flosequinan 100, 150 mg/d (n=207) vs. (n=104) | NYHA II-IV | double blind Parallel groups Sample size: 207/104 Primary endpoint: Exercise tolerance FU duration: 3 months |
|
| phosphodiesterase III inhibitors | ibopamine | versus placebo or control No demonstrated result for efficacy ibopamine inferior to placebo in terms of Total mortality in PRIME II, 1997 ibopamine inferior to placebo in terms of Sudden death in PRIME II, 1997 | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| PRIME II, 1997 | ibopamine vs placebo | | Total mortality 1.20 [1.02; 1.42] Sudden death 1.50 [1.04; 2.15] | Cardiac death 0.71 [0.37; 1.38] Transplantation 0.95 [0.53; 1.72] |
| Trial | Treatments | Patients | Method |
|---|
| PRIME II, 1997 | oral ibopamine 100 mg three times daily (n=953) vs. placebo (n=953) | patients with heart failure NYHA III-IV | double blind Parallel groups Sample size: 953/953 Primary endpoint: Total mortality FU duration: mean 11.4 months |
|
| phosphodiesterase III inhibitors | Milrinone | versus placebo or control No demonstrated result for efficacy Milrinone inferior to placebo in terms of Total mortality in PROMISE, 1991 Milrinone inferior to placebo in terms of Sudden death in PROMISE, 1991 Milrinone inferior to placebo in terms of Cardiac death in PROMISE, 1991 Milrinone inferior to placebo in terms of Vertigo in PROMISE, 1991 | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| PROMISE, 1991 | Milrinone vs placebo | | Total mortality 1.24 [1.02; 1.51] Sudden death 1.57 [1.14; 2.17] Cardiac death 1.30 [1.06; 1.60] Vertigo 1.90 [1.40; 2.57] | Myocardial infarction (fatal & non fatal) 5.64 [0.68; 46.66] Worsening heart failure (requiring intervention) 1.88 [0.65; 5.46] Transplantation 0.63 [0.11; 3.73] Arrhythmia 1.22 [0.95; 1.56] | | MMTG, 1989 | Milrinone vs placebo | | | Total mortality 2.33 [0.94; 5.80] Myocardial infarction (fatal & non fatal) ∞ [NaN; ∞] Cardiac death 1.87 [0.72; 4.80] Worsening heart failure (requiring intervention) 0.87 [0.57; 1.34] Arrhythmia 1.87 [0.91; 3.81] Vertigo 2.05 [0.74; 5.72] |
| Trial | Treatments | Patients | Method |
|---|
| PROMISE, 1991 | Milrinone 40mg/d (n=561) vs. placebo (n=527) | NYHA III,IV | double blind Parallel groups Sample size: 561/527 Primary endpoint: Total mortality FU duration: 20 months | | MMTG, 1989 | Milrinone <40mg/d (n=119) vs. placebo (n=111) | NYHA II-IV | double blind Parallel groups Sample size: 119/111 Primary endpoint: none FU duration: 3 months |
|
| phosphodiesterase III inhibitors | vesnarinone | versus placebo or control No demonstrated result for efficacy Vesnarinone inferior to placebo in terms of Total mortality in VEST, 1998 Vesnarinone inferior to placebo in terms of Sudden death in VEST, 1998 | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| OPC-8212 MRG, 1990 | Vesnarinone vs placebo | | | Total mortality 0.00 [0.00; NaN] Worsening heart failure (requiring intervention) 0.14 [0.02; 1.12] Arrhythmia ∞ [NaN; ∞] Vertigo ∞ [NaN; ∞] | | VEST, 1998 | Vesnarinone vs placebo | | Total mortality 1.16 [1.02; 1.33] Sudden death 1.26 [1.03; 1.54] | Myocardial infarction (fatal & non fatal) 1.41 [0.51; 3.90] Cardiac death 1.13 [0.98; 1.30] Worsening heart failure (requiring intervention) 0.95 [0.85; 1.05] | | VSG, 1993 | Vesnarinone vs placebo | Total mortality 0.39 [0.21; 0.73] Sudden death 0.20 [0.06; 0.68] Cardiac death 0.36 [0.19; 0.68] Worsening heart failure (requiring intervention) 0.54 [0.31; 0.94] | | Myocardial infarction (fatal & non fatal) 1.00 [0.33; 3.04] Transplantation 0.46 [0.18; 1.19] Arrhythmia 2.99 [0.31; 28.52] |
| Trial | Treatments | Patients | Method |
|---|
| OPC-8212 MRG, 1990 | Vesnarinone 60mg/d (n=45) vs. placebo (n=48) | NYHA II-IV | double blind Parallel groups Sample size: 45/48 Primary endpoint: none FU duration: 3 months | | VEST, 1998 | Vesnarinone 30, 60mg/d (n=2550) vs. placebo (n=1283) | NYHA III,IV | double blind Parallel groups Sample size: 2550/1283 Primary endpoint: Total mortality FU duration: 9 months | | VSG, 1993 | Vesnarinone 60mg/d (n=-9) vs. placebo (n=-9) | NYHA II-IV | double blind Parallel groups Sample size: -9/-9 Primary endpoint: total mortality or major cardiovascular morbidity FU duration: 6 months |
|
| relaxine | serelaxin | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Pre-RELAX-AHF, 2009 | serelaxin vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Pre-RELAX-AHF, 2009 | intravenous relaxin for 48 hours: 10µg/kg daily, 30µg/kg daily, 100µg/kg daily, 250µg/kg daily (n=172) vs. placebo (n=62) | Patients hospitalized with acute heart failure | double blind Parallel groups Sample size: 172/62 Primary endpoint: none defined FU duration: dose-finding phase IIb study |
|
| renin inhibitor | aliskiren | versus No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ASTRONAUT, 2013 | Aliskiren vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| ASTRONAUT, 2013 | Aliskiren (n=1639) vs. placebo (n=0) | stable patients with heart failure, an LVEF <40% (mean 28%), and elevated natriuretic peptides who had been discharged from a heart-failure hospitalization an average of five days before | double blind Parallel groups Sample size: 1639/0 Primary endpoint: CV death or HF re-hospitalization FU duration: 6 months |
|
| vasodilators therapy | epoprostenol | versus placebo or no treatment No demonstrated result for efficacy epoprostenol inferior to standard care in terms of All cause death in FIRST, 1997 | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| FIRST, 1997 | epoprostenol vs standard care | | All cause death 1.29 [1.05; 1.60] | |
| Trial | Treatments | Patients | Method |
|---|
| FIRST, 1997 | epoprostenol infusion (n=237) vs. standard care (n=234) | Patients with class IIIB/IV congestive
heart failure and decreased left ventricular ejection fraction | NA Parallel groups Sample size: 237/234 Primary endpoint: all cause death FU duration: 3 and 6 months |
|
| vasodilators therapy | hydralazine | versus placebo or no treatment No demonstrated result for efficacy | 4 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| hydralazine vs control | | | | | hydralazine vs placebo | | | | | hydralazine vs placebo | | | | | hydralazine vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Chatterjee, 1980 | oral hydralazine (n=-9) vs. NA (n=-9) | patients with chronic CHF | Sample size: -9/-9 Primary endpoint: FU duration: | | Franciosa, 1982 | hydralazine 200 mg daily (n=16) vs. placebo (n=16) | patients with class III and IV symptoms while they were taking digitalis and diuretics | double blind Sample size: 16/16 Primary endpoint: FU duration: 20 weeks | | Conradson , 1984 | hydralazine (n=-9) vs. placebo (n=-9) | patients with chronic congestive heart failure (NYHA class III) | Sample size: -9/-9 Primary endpoint: FU duration: 1 year | | Magorien , 1984 | hydralazine 100 mg orally every eight hours (n=-9) vs. placebo (n=-9) | patients with idiopathic dilated cardiomyopathy | double blind Sample size: -9/-9 Primary endpoint: FU duration: |
|
| vasodilators therapy | hydralazine-ISDN | versus placebo or no treatment No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| VHeFT I (hydralazine ISDN), 1986 | hydralazine-ISDN vs placebo | | | All cause death 0.88 [0.70; 1.10] |
| Trial | Treatments | Patients | Method |
|---|
| VHeFT I (hydralazine ISDN), 1986 | hydralazine 300mg/d ISDN 160mg/d (n=186) vs. placebo (n=273) | patienst with chronic congestive heart failure and cardiac dilatation (CT ratio>0.55) or LVEF <45% in association with reduced exercise tolerance | double blind Parallel groups Sample size: 186/273 Primary endpoint: FU duration: 2.3 y (range 0.5-5.7 years) |
|
| vasodilators therapy | isosorbide dinitrate | versus placebo or no treatment No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| isosorbide dinitrate vs placebo | | | | | isosorbide dinitrate vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| NICE (Lewis), 1999 | isosorbide-5-mononitrate 50 mg once daily (n=-9) vs. placebo (n=-9) | patients (NYHA Class 2-3) treated for heart failure, all receiving captopril and most also furosemide | Sample size: -9/-9 Primary endpoint: FU duration: 12 weeks | | Franciosa , 1978 | isosorbide dinitrate (n=16) vs. placebo (n=16) | | double blind Sample size: 16/16 Primary endpoint: FU duration: |
|
| vasodilators therapy | levosimendan | versus placebo or control No demonstrated result for efficacy | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| REVIVE II, 2013 | levosimendan vs placebo | | | | | REVIVE-I, 2003 | levosimendan vs placebo | | | | | RUSSLAN, 2002 | levosimendan vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| REVIVE II, 2013 | Intravenous Levosimendan (n=299) vs. placebo (n=301) | patients with decompensated chronic heart failure | double blind Parallel groups Sample size: 299/301 Primary endpoint: worsening heart failure FU duration: 5 days | | REVIVE-I, 2003 | levosimendan 0.1–0.2 mg/kg/min (n=-9) vs. placebo (n=-9) | patienst with HF andsymptoms at rest | Parallel groups Sample size: -9/-9 Primary endpoint: composite clinical FU duration: | | RUSSLAN, 2002 | Levosimendan at different doses (0.1-0.4 microg x kg(-1) x min(-1)) for 6h (n=-9) vs. placebo (n=-9) | patients with left ventricular failure complicating acute myocardial infarction | double-blind Parallel groups Sample size: -9/-9 Primary endpoint: hypotension or myocardial ischaemia FU duration: 14 days |
|
| vasodilators therapy | levosimendan | versus active treatment No demonstrated result for efficacy | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| SURVIVE, 2007 | levosimendan vs dobutamine | | | all cause death (6M+) 0.91 [0.74; 1.12] Short term death (30d) 0.85 [0.63; 1.15] | | CASINO | levosimendan vs dobutamine | | | | | LIDO, 2002 | levosimendan vs dobutamine | | | |
| Trial | Treatments | Patients | Method |
|---|
| SURVIVE, 2007 | Intravenous levosimendan (n=664) vs. intravenous dobutamine (n=663) | patients hospitalized with acute decompensated heart failure who required inotropic support | double-blind Parallel groups Sample size: 664/663 Primary endpoint: all cause mortality FU duration: 180 days | | CASINO | Levosimendan 16 mg/kg þ 0.2 mg/kg/min (n=-9) vs. Dobutamine (10 mg/kg/min) and placebo (n=-9) | patients withdecompensatedlow-output HF | Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: | | LIDO, 2002 | Levosimendan (n=-9) vs. Dobutamine (n=-9) | patients with low-output heart failure | double-blind Parallel groups Sample size: -9/-9 Primary endpoint: haemodynamic improvement FU duration: 24h |
|
| vasodilators therapy | nesiritide | versus placebo or control No demonstrated result for efficacy nesiritide inferior to placebo in terms of amelioration of Dyspnea at 24 h in ASCEND-HF, 2011 | 7 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| NSGET (efficacy trial), 2000 | nesiritide vs placebo | | | all cause death 1.48 [0.31; 7.03] | | PROACTION, 2003 | nesiritide vs placebo | | | all cause death 4.88 [0.58; 41.10] | | BNP-CARDS, 2007 | nesiritide vs placebo | | | | | FUSION 2, 2008 | nesiritide vs placebo | | | | | ASCEND-HF, 2011 | nesiritide vs placebo | | amelioration of Dyspnea at 24 h 1.11 [1.03; 1.19] | all cause death 0.90 [0.71; 1.14] 30-d HF rehospitalization
0.98 [0.82; 1.19] 30-d death or HF hospitalization 0.93 [0.81; 1.08] 30 day death 0.90 [0.71; 1.14] | | VMAC (intravenous neseritide), 2002 | nesiritide vs placebo | | | | | NSGET (comparative trial), 2000 | nesiritide vs control | | | |
| Trial | Treatments | Patients | Method |
|---|
| NSGET (efficacy trial), 2000 | nesiritide(0.015 and 0.030 microg/kg/min (n=85) vs. placebo (n=42) | acutely decompensated heart failure requiring invasive monitoring | Sample size: 85/42 Primary endpoint: FU duration: | | PROACTION, 2003 | nesiritidefor at least 12h (n=127) vs. placebo (n=123) | patients presenting to the ED with acutely decompensated
HF and dyspnea at rest or with minimal activity | double-blind Parallel groups Sample size: 127/123 Primary endpoint: FU duration: 30 days | | BNP-CARDS, 2007 | nesiritide as a 0.01-µg/kg/min infusion for 48 hours (n=39) vs. placebo (n=36) | acute decompensated heart failure with moderate to severe renal insufficiency | Double blind Parallel groups Sample size: 39/36 Primary endpoint: >20% increase in SCr anytime during 1st hospital week FU duration: 7 days | | FUSION 2, 2008 | nesiritide (2 µg/kg bolus plus 0.01 µg/kg-per-minute infusion for four to six hours) (n=911) vs. placebo (n=0) | patients with ACC/AHA stage C/D heart failure with two recent heart-failure hospitalizations, an ejection fraction of less than 40%, and NYHA class 4 symptoms or NYHA class 3 symptoms with creatinine clearance less than 60 mL/min | double-blind Parallel groups Sample size: 911/0 Primary endpoint: mortality and CV or renal hospitalization FU duration: 12 weeks | | ASCEND-HF, 2011 | intravenous nesiritide for 24 hours to 7 days on top of standard therapy (n=3496) vs. matching placebo (n=3511) | Patients hospitalized for heart
failure (within 24 hours of hospitalization and institution of acute IV therapy for ADHF) | double-blind Parallel groups Sample size: 3496/3511 Primary endpoint: coprimary: dyspnea, death or HF hospitalization FU duration: 30 days | | VMAC (intravenous neseritide), 2002 | intravenous nesiritidefor 3 hours (n=204) vs. placebo (n=142) 3rd arms with IV nitroglycerin for 3 hours(n=143) | acutely decompensated heart failure requiring hospitalization
| double-blind Sample size: 204/142 Primary endpoint: FU duration:
| | NSGET (comparative trial), 2000 | nesiritide(0.015 and 0.030 microg/kg/min (n=203) vs. usual care (n=102)
| acutely decompensated heart failure requiring invasive monitoring
| open Parallel groups Sample size: 203/102 Primary endpoint: FU duration: <5 days
|
|
| vasodilators therapy | nesiritide | versus active treatment No demonstrated result for efficacy | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| VMAC (24h), 2002 | nesiritide vs nitroglycerin | | | all cause death 1.56 [0.80; 3.04] | | FUSION 1, 2004 | nesiritide vs standard care | | | | | PRECEDENT, 2002 | nesiritide vs dobutamine | | | |
| Trial | Treatments | Patients | Method |
|---|
| VMAC (24h), 2002 | nesiritideinfusion for 24 hours (n=280) vs. nitroglycerin (n=218) | acutely decompensated heart failure requiring hospitalization | Sample size: 280/218 Primary endpoint: FU duration: | | FUSION 1, 2004 | nesiritide 0.005 microg/kg/min or 0.010 microg/kg/min once weekly (n=-9) vs. standard care (n=-9) | outpatient with co-morbid advanced heart failure and renal insufficiency | open Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: 12 weeks | | PRECEDENT, 2002 | nesiritide(0.015 or 0.03 microg/kg/min) (n=-9) vs. Dobutamine (> or =5 microg/kg/min) (n=-9) | Symptomatic, Decompensated CHF | open Parallel groups Sample size: -9/-9 Primary endpoint: ECG Holter FU duration: |
|
| vasopeptidase inhibitor | omapatrilat | versus angiotensin-converting enzyme inhibitors No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| OVERTURE, 2002 | omapatrilat vs enalapril | | | | | IMPRESS, 2000 | omapatrilat vs lisinopril | hospitalization for heart failure 0.44 [0.19; 0.99] death or hospitalization for heart failure 0.52 [0.27; 1.00] | | all cause death 0.69 [0.27; 1.78] |
| Trial | Treatments | Patients | Method |
|---|
| OVERTURE, 2002 | omapatrilat 40 mg once dailyitm (n=2886) vs. enalapril 10 mg twice daily (n=2884) | patients with NYHA II-IV heart failure | double blind Parallel groups Sample size: 2886/2884 Primary endpoint: death or hospitalization for HF requiring intravenous treatment FU duration: 14.5 months | | IMPRESS, 2000 | omapatrilat target
dose 40 mg daily (n=289) vs. lisinopril target dose 20mg daily (n=284) | patients with NTHA II-IV congestive heart failure, LEVF <=40%, and receiving ACE inhibitor | double blind Parallel groups Sample size: 289/284 Primary endpoint: improvement in maximum exercise treadmill test FU duration: 12 weeks (24 weeks) |
|
| vasopressin antagonist | tolvaptan | versus placebo or control No demonstrated result for efficacy | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| EVEREST Clinical Status , 2007 | tolvaptan vs placebo | | | | | EVEREST Outcome, 2007 | tolvaptan vs placebo | | | | | Udelson, 2007 | tovalpan vs placebo | heart failure hospitalization 0.62 [0.38; 1.00] | | death 0.55 [0.21; 1.43] |
| Trial | Treatments | Patients | Method |
|---|
| EVEREST Clinical Status , 2007 | (n=-9) vs. (n=-9) | patients hospitalized with heart failure | Sample size: -9/-9 Primary endpoint: composite of global clinical status visual analog scale and body weight at short term FU duration: | | EVEREST Outcome, 2007 | (n=-9) vs. (n=-9) | patients hospitalized with heart failure | Sample size: -9/-9 Primary endpoint: FU duration: | | Udelson, 2007 | tolvaptan 30 mg/day (n=120) vs. placebo (n=120) | patients with HF and reduced systolic function | double blind Parallel groups Sample size: 120/120 Primary endpoint: left ventricular end-diastolic volume FU duration: 1 year |
|
