| mechanism | treatment | Demonstrated benefit and harm | k | | | |
|---|
| anti-anginal drugs | ivabradine | versus placebo or control No demonstrated result for efficacy | 5 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ivabradine 5mg vs placebo | | | | | ivabradine 15mg vs placebo | | | | | ivabradine 10mg vs placebo | | | | | ivabradine 20mg vs placebo | | | | | ivabradine 15mg vs placebo (on top standard treatment) | | | |
| Trial | Treatments | Patients | Method |
|---|
| Borer (CL2-009) 5mg, 2003 | (n=90) vs. (n=91) | | double blind Parallel groups Sample size: 90/91 Primary endpoint: FU duration: 2 weeks | | BEAUTIFUL, 2008 | ivabradine target dose of 7·5 mg twice a day
(n=5479) vs. placebo
(n=5438)
| patients with coronary artery disease and left-ventricular systolic
dysfunction (LVEF <=40%)
| double blind Sample size: 5479/5438 Primary endpoint: Cvdeath, MI, hospitalization for HF FU duration: 19 months (range 16-24)
| | Borer (CL2-009) 10mg, 2003 | Ivabradine 5 mg twice daily (10mg/d)
(n=91) vs. placebo
(n=91)
|
| double blind Sample size: 91/91 Primary endpoint: FU duration: 2 weeks
| | Borer (CL2-009) 20mg, 2003 | ivabradine 10mg twice daily (20mg/d)
(n=88) vs. placebo
(n=91)
|
| double blind Sample size: 88/91 Primary endpoint: FU duration: 2 weeks
| | BEAUTIFUL (angina subgroup) | ivabradine target dose of 7·5 mg twice a day
(n=734) vs. placebo
(n=773)
| patients with stable
coronary artery disease and left ventricular
systolic dysfunction with limiting angina
| double blind Sample size: 734/773 Primary endpoint: Cvdeath, MI, hospitalization for HF FU duration: 19 months (range 16-24) post hoc analysis
|
|
| anti-anginal drugs | ivabradine | versus beta-blockers No demonstrated result for efficacy | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ivabradine 20mg vs atenolol | | | | | ivabradine 15mg vs placebo on top of atenolol | | | | | ivabradine 15mg vs atenolol | | | |
| Trial | Treatments | Patients | Method |
|---|
| INITIATIVE (CL3-017, Tardif) 20mg, 2005 | ivabradine 5 mg bid for 4 weeks and then 10 mg bid for 12 weeks
(n=317) vs. atenolol 50 mg od for 4 weeks and then 100 mg od for 12 weeks
(n=307) 3 arms: ivabradine 15, 20 mg/d and atenolol 100mg/d
| patients with stable angina
| double-blind Parallel groups Sample size: 317/307 Primary endpoint: FU duration: 16 weeks
| | ASSOCIATE (Tardif), 2009 | ivabradine 5 mg b.i.d. for 2 months, increased to 7.5 mg b.i.d. for a further 2 months (on top atenolol 50 mg/day )
(n=449) vs. placebo on top atenolol 50 mg/day
(n=440)
| patients with stable angina receiving atenolol 50 mg/day or another beta-blocker at equivalent doses for at least
3 months
| double blind Parallel groups Sample size: 449/440 Primary endpoint: total exercise duration FU duration: 4 months
| | INITIATIVE (CL3-017, Tardif) 15mg, 2005 | ivabradine 5 mg bid for 4 weeks and then either 7.5 or 10 mg bid for 12 weeks
(n=315) vs. atenolol 50 mg od for 4 weeks and then 100 mg od for 12 weeks
(n=307) 3 arms: ivabradine 15, 20 mg/d and atenolol 100mg/d
| patients with stable angina
| double-blind Sample size: 315/307 Primary endpoint: FU duration: 16 weeks
|
|
| anti-anginal drugs | ivabradine | versus calcium blockers No demonstrated result for efficacy | 6 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ivabradine 15mg vs amlodipine | | | | | ivabradine 15mg vs placebo on top of amlodipine | | | | | ivabradine 10mg vs placebo on top of amlodipine | | | | | ivabradine vs amlodipine | | | | | ivabradine vs amlodipine | | | | | Ruzyllo (CL3-023) 20mg, 2007 | ivabradine 20mg vs amlodipine | | | |
| Trial | Treatments | Patients | Method |
|---|
| Ruzyllo (CL3-023) 15mg, 2007 | ivabradine 7.5mg twice daily (n=400) vs. amlodipine 10mg once daily (n=404) | Patients with a >/=3-month history of chronic, stable effort-induced angina | double-blind Parallel groups Sample size: 400/404 Primary endpoint: total exercise duration FU duration: 3 months | | CL3-018 15mg | ivabradine 7.5mg twice daily (15mg/d) (n=244) vs. placebo (n=252) | | Sample size: 244/252 Primary endpoint: FU duration: | | CL3-018 10mg | ivabradine 5mg twice daily (10mg/d) (n=232) vs. placebo (n=252) | | Parallel groups Sample size: 232/252 Primary endpoint: FU duration: 12 weeks | | CL3-023 (15mg) | ivabradine 7.5mg twice daily
(n=381) vs. amlodipine
(n=398) 3 arms: ivabradine 15 and 20 mg, amlodipine
|
| double-blind Parallel groups Sample size: 381/398 Primary endpoint: FU duration: 3 months
| | CL3-023 (20mg) | ivabradine 10mg twice daily
(n=376) vs. amlodipine
(n=398)
|
| double-blind Sample size: 376/398 Primary endpoint: FU duration: 3 months
| | Ruzyllo (CL3-023) 20mg, 2007 | ivabradine 10mg twice daily (n=391) vs. amlodipine 10mg once daily (n=404)
| Patients with a >/=3-month history of chronic, stable effort-induced angina
| double-blind Parallel groups Sample size: 391/404 Primary endpoint: total exercise duration FU duration: 3 months
|
|
| anti-anginal drugs | nicorandil | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Nishimura, 2009 | nicorandil vs control | | | |
| Trial | Treatments | Patients | Method |
|---|
| Nishimura, 2009 | nicorandil 15 mg daily (n=-9) vs. control (n=-9) | Maintenance hemodialysis patients who underwent percutaneous coronary artery intervention and had complete coronary revascularization (absence of both restenosis and de novo coronary lesion) at coronary arteriography 6 months later | open Parallel groups Sample size: -9/-9 Primary endpoint: cardiac death FU duration: 2.7 years |
|
| anti-anginal drugs | ranolazine | versus placebo or control No demonstrated result for efficacy | 4 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ERICA, 2006 | ranolazine 1000mg + amlodipine vs placebo + amlodipine | | | | | MARIZA, 2004 | ranolazine 1000mg vs placebo | | | | | RAN080, 2005 | ranolazine 1000mg vs placebo | | | | | CARISA 1000mg, 2004 | ranolazine 1000mg vs placebo (on top standard treatment) | | | Death from any cause 0.33 [0.03; 3.12] |
| Trial | Treatments | Patients | Method |
|---|
| ERICA, 2006 | ranolazine 1000 mg twice a day for 6 weeks + amlodipine (10 mg/d) (n=281) vs. placebo + amlodipine (10 mg/d) (n=284) | patients with stable chronic angina already treated with the maximal dose of amlodipine (10mg/d) | double blind Parallel groups Sample size: 281/284 Primary endpoint: angina frequency FU duration: 6 weeks | | MARIZA, 2004 | ranolazine 500 mg twice daily (sustained-release ranolazine 500, 1,000, or 1,500 mg) (n=191) vs. placebo (n=191) cross over 4 period with Ranolazine ER 500,1,000, or 1,500 mg or placebo twice a day as monotherapy
for 1 week each | Patients with angina-limited exercise | double blind Cross over Sample size: 191/191 Primary endpoint: Exercise duration FU duration: 1 week | | RAN080, 2005 | ranolazine IR 400mg TID (n=158) vs. placebo (n=158) cross over 3 periods with Ranolazine IR 400 mg
TID, atenolol 100 mg
QD and placebo for 1
week each | patients who had symptom-limited exercise | double blind Cross over Sample size: 158/158 Primary endpoint: Time to onset of angina during exercise testing FU duration: 1 week | | CARISA 1000mg, 2004 | ranozaline 1000mg (in combination with beta-blockers or calcium antagonists) (n=261) vs. placebo (n=258) 3rd arm receiving ranolazine 1000mg twice daily
| patients with severe chronic angina who have symptoms of chronic angina and who experience angina and ischemia at low workloads despite taking standard doses of atenolol, amlodipine, or diltiazem
| double blind Parallel groups Sample size: 261/258 Primary endpoint: exercise tolerance and angina frequency FU duration: 12 weeks
|
|
| antibiotics | Azithromycin | versus placebo or control No demonstrated result for efficacy | 6 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Gupta et al, 1997 | Azithromycin vs placebo | | | all cause death 0.50 [0.03; 7.59] Acute coronary syndrome (MI ou unstable angina) 0.64 [0.19; 2.09] | | ACADEMIC, 1999 | Azithromycin vs placebo | | | all cause death 1.25 [0.34; 4.56] Myocardial infarction (fatal & non fatal) 0.68 [0.19; 2.35] Acute coronary syndrome (MI ou unstable angina) 0.94 [0.44; 1.98] | | WIZARD, 2003 | Azithromycin vs placebo | | | all cause death 0.93 [0.76; 1.14] Myocardial infarction (fatal & non fatal) 0.95 [0.76; 1.18] Acute coronary syndrome (MI ou unstable angina) 0.97 [0.82; 1.15] | | ACES, 2005 | Azithromycin vs placebo | | | all cause death 1.07 [0.85; 1.34] Myocardial infarction (fatal & non fatal) 1.04 [0.82; 1.31] Acute coronary syndrome (MI ou unstable angina) 1.01 [0.83; 1.22] | | STAMINA (Azithromycin), 2002 | Azithromycin vs placebo | | | all cause death 0.96 [0.29; 3.24] Acute coronary syndrome (MI ou unstable angina) 0.72 [0.45; 1.14] | | AZACS, 2003 | Azithromycin vs placebo | | | all cause death 1.07 [0.86; 1.32] Myocardial infarction (fatal & non fatal) 0.78 [0.42; 1.46] |
| Trial | Treatments | Patients | Method |
|---|
| Gupta et al, 1997 | Azithromycin 500 mg/d for 3 d (28 received 1 course, 12 received 2 courses 3 mo apart) (n=43) vs. placebo (n=41) | Male patients at least 6 mo from documented MI and with titers to Chlamydia pneumoniae >=1:64 | double blind Parallel groups Sample size: 43/41 Primary endpoint: not defined FU duration: 18mo | | ACADEMIC, 1999 | Azithromycin 500 mg/d for 3 d then 500 mg/wk for 3 mo (n=150) vs. placebo (n=152) | Patients with CAD and C pneumoniae titers of >=1:16. Patients were at least 5 d from an MI | double blind Parallel groups Sample size: 150/152 Primary endpoint: CV death, MI, stroke, unstable angina, revascularization FU duration: 2y | | WIZARD, 2003 | Azithromycin 600 mg/d for 3 d then 1/wk for 11 wk (n=3879) vs. placebo (n=3868) | Patients with a history of MI of more than 6 weeks before and with C pneumoniae titers of >=1:16 | double blind Parallel groups Sample size: 3879/3868 Primary endpoint: coronary events FU duration: 14mo | | ACES, 2005 | Azithromycin 600 mg/wk for 1 y (n=2004) vs. placebo (n=2008) | Patients with stable CAD | double blind Parallel groups Sample size: 2004/2008 Primary endpoint: coronary events FU duration: 4y | | STAMINA (Azithromycin), 2002 | Azithromycin 500 mg/d for 3 d plus omeprazole 20 mg 2/d for 1 wk plus metronidazole 400 mg 2/d for 1 wk (n=111) vs. placebo (n=107) | Patients with ACS | double blind Parallel groups Sample size: 111/107 Primary endpoint: not defined FU duration: 1y | | AZACS, 2003 | Azithromycin 500 mg on day 1 followed by 250 mg/d for 4d (n=2004) vs. placebo (n=2008) | Patients with ACS | double blind Parallel groups Sample size: 2004/2008 Primary endpoint: death, MI, revascularization FU duration: 6mo |
|
| antibiotics | clarithromycin | versus placebo or control No demonstrated result for efficacy clarithromycin inferior to placebo in terms of CV events in CLARICOR, 2006 | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| CLARIFY, 2001 | clarithromycin vs placebo | Acute coronary syndrome (MI ou unstable angina) 0.40 [0.21; 0.77] | | all cause death 1.00 [0.30; 3.31] Myocardial infarction (fatal & non fatal) 0.52 [0.19; 1.37] | | CLARICOR, 2006 | clarithromycin vs placebo | | CV events 1.17 [1.02; 1.35] | all cause death 1.17 [0.96; 1.44] coronary events 1.14 [0.99; 1.31] Acute coronary syndrome (MI ou unstable angina) 1.10 [0.88; 1.36] |
| Trial | Treatments | Patients | Method |
|---|
| CLARIFY, 2001 | Clarithromycin 500 mg/d for 85 d (n=74) vs. placebo (n=74) | Patients with ACS | double blind Parallel groups Sample size: 74/74 Primary endpoint: death, MI, unstable angina FU duration: 1y | | CLARICOR, 2006 | clarithromycin 500 mg/day (n=2172) vs. placebo (n=2201) | patients with adischarge diagnosis of myocardial infarction or angina pectoris | double blind Parallel groups Sample size: 2172/2201 Primary endpoint: death, MI, unstable angina FU duration: 3 years |
|
| antithrombotics | aspirin | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| SAPAT, 1992 | aspirin vs placebo | Non fatal MI 0.67 [0.45; 0.98] vascular event 0.71 [0.57; 0.89] | | vascular death 0.76 [0.54; 1.07] Non fatal stroke 0.79 [0.45; 1.39] non vascular death 1.66 [0.79; 3.51] |
| Trial | Treatments | Patients | Method |
|---|
| SAPAT, 1992 | aspirin 75 mg daily (n=1009) vs. placebo (n=1026) | patients with stable chronic angina pectoris | double blind Parallel groups Sample size: 1009/1026 Primary endpoint: myocardial infarction and sudden death FU duration: 50 months |
|
| antithrombotics | clopidogrel | versus aspirin No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ASCET | clopidogrel vs aspirin | | | vascular event 0.90 [0.63; 1.29] |
| Trial | Treatments | Patients | Method |
|---|
| ASCET | clopidogrel 75 mg once daily for two years (n=498) vs. Aspirin 160 mg once daily for two years (n=503) | patients with documented coronary heart disease and treated with aspirin platelet function was also assessed at randomization with the PFA100 method and platelet aggregometry | open Parallel groups Sample size: 498/503 Primary endpoint: all-cause death, nonfatal MI, ischemic stroke, and unstable angina FU duration: |
|
| antithrombotics | dipyridamol | versus placebo or control No demonstrated result for efficacy | 10 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Atlanta (Sbar), 1967 | dipyridamol vs control | | | vascular death ∞ [NaN; ∞] Non fatal stroke ∞ [NaN; ∞] Non fatal MI 0.75 [0.18; 3.07] non vascular death NaN [NaN; NaN] vascular event 1.25 [0.37; 4.21] | | Becker, 1967 | dipyridamol vs control | | | vascular death ∞ [NaN; ∞] Non fatal stroke NaN [NaN; NaN] Non fatal MI NaN [NaN; NaN] non vascular death NaN [NaN; NaN] vascular event ∞ [NaN; ∞] | | Wirecki, 1967 | dipyridamol vs control | | | vascular death NaN [NaN; NaN] Non fatal stroke NaN [NaN; NaN] Non fatal MI NaN [NaN; NaN] non vascular death NaN [NaN; NaN] vascular event NaN [NaN; NaN] | | dipyridamol vs placebo | | | | | dipyridamol vs placebo | | | | | dipyridamol vs placebo | | | | | dipyridamol vs placebo | | | | | dipyridamol vs placebo | | | | | dipyridamol vs placebo | | | | | dipyridamol vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Atlanta (Sbar), 1967 | dipyridamole 150mg daily (n=30) vs. placebo (n=30) | patients with angina pectoris | double-blind parallel groups Sample size: 30/30 Primary endpoint: not defined FU duration: 6 months | | Becker, 1967 | dipyridamole 225mg daily (n=14) vs. placebo (n=13) | | double-blind parallel groups Sample size: 14/13 Primary endpoint: not defined FU duration: 5 months | | Wirecki, 1967 | dipyridamole 150mg daily (n=28) vs. placebo (n=28) | patients with angina pectoris | double blind parallel groups Sample size: 28/28 Primary endpoint: not defined FU duration: 7 months | | Igloe, 1970 | Dipyridamole 200mg daily (n=26) vs. placebo (n=22) | patients with angina pectoris | double blind parallel groups Sample size: 26/22 Primary endpoint: not defined FU duration: 2-7 months | | Zion, 1961 | Dipyridamole 37.5mg (n=14) vs. placebo (n=14) | patients with angina pectoris | double-blind cross-over Sample size: 14/14 Primary endpoint: not defined FU duration: 0.5 months | | Kinsella, 1962 | dipyridamole 37.5 mg and 100mg daily (n=13) vs. placebo (n=13) | | double-blind parallel groups Sample size: 13/13 Primary endpoint: not defined FU duration: 0.5 months | | Leiberman, 1964 | dipyridamole 100mg daily (n=19) vs. placebo (n=19) | | double blind parallel groups Sample size: 19/19 Primary endpoint: not defined FU duration: >3 months | | Dewar, 1961 | Dipyridamole 100mg daily (n=17) vs. placebo (n=17) | patients with angina pectoris | double-blind parallel groups Sample size: 17/17 Primary endpoint: not defined FU duration: 0.5 months | | Neumann, 1964 | dipyridamole 150mg daily (n=20) vs. placebo (n=16) | elderly with precordial pain | double-blind parallel groups Sample size: 20/16 Primary endpoint: not defined FU duration: 1.5 months | | Foulds, 1960 | Dipyridamole 200mg daily (n=24) vs. placebo (n=24) | patients with angina pectoris | double-blind parallel groups Sample size: 24/24 Primary endpoint: not defined FU duration: 1 months |
|
| antithrombotics | ticlopidine | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Berglund, 1985 | ticlopidine vs placebo | | | vascular death NaN [NaN; NaN] Non fatal stroke NaN [NaN; NaN] Non fatal MI NaN [NaN; NaN] non vascular death NaN [NaN; NaN] vascular event NaN [NaN; NaN] |
| Trial | Treatments | Patients | Method |
|---|
| Berglund, 1985 | ticlopidine 500 mg daily (n=21) vs. placebo (n=17) | middle-aged men with stable incapacitating angina pectoris | double blind parallel groups Sample size: 21/17 Primary endpoint: not defined FU duration: 2m |
|
| HR-slowing agents | ivabradine | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ivabradine 20mg vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| SIGNIFY, 2014 | ivabradine, at a dose of up to 10 mg twice daily, with the dose adjusted to achieve a target heart rate of 55 to 60 beats per minute. (n=9550) vs. placebo (n=9552) | patients who had both stable coronary artery disease without clinical heart failure and a heart rate of 70 beats per minute or more | double-blind Parallel groups Sample size: 9550/9552 Primary endpoint: death from cardiovascular FU duration: 27.8 mo (median) |
|
| myocardial revascularization | angioplasty | versus surgery No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| AMIST (Reeves), 2004 | angioplasty vs MIDCAB | | | |
| Trial | Treatments | Patients | Method |
|---|
| AMIST (Reeves), 2004 | percutaneous transluminal coronary angioplasty (PTCA) with or without stenting (n=50) vs. minimally invasive direct coronary artery bypass grafting (MIDCAB) (n=50) | single-vessel disease (at least 50% stenosis) of the left anterior descending coronary artery (LAD). | open Parallel groups Sample size: 50/50 Primary endpoint: cardiac-related events FU duration: 12 months |
|
| myocardial revascularization | Coronary Artery Bypass Surgery | versus no TMR No demonstrated result for efficacy | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Allen, 2000 | TMR+CABG vs CABG | | | | | Loubani, 2003 | TMR+CABG vs CABG | | | | | Zhao, 2006 | TMR+CABG vs CABG | | | |
| Trial | Treatments | Patients | Method |
|---|
| Allen, 2000 | coronary bypass of suitable vessels plus transmyocardial revascularization to areas not graftable (n=132) vs. coronary bypass alone with nongraftable areas left unrevascularized (n=131) | patients whose standard of care was coronary artery bypass grafting and who had one or more ischemic areas not amenable to bypass grafting | single blind Sample size: 132/131 Primary endpoint: FU duration: | | Loubani, 2003 | coronary artery bypass grafting plus transmyocardial laser revascularization with a holmium:YAG (yttrium-aluminum-garnet) laser to nongraftable areas (n=10) vs. coronary artery bypass grafting (n=10) | Patients who had elective coronary artery bypass with one or more nongraftable coronary arteries | open Parallel groups Sample size: 10/10 Primary endpoint: none defined FU duration: 36 months | | Zhao, 2006 | transmyocardial laser revascularization (holmium: YAG) combined with off-pump coronary artery bypass (n=40) vs. off-pump coronary artery bypass (n=40) | patients with diffusely diseased target vessels | open Parallel groups Sample size: 40/40 Primary endpoint: not defined FU duration: 3.4y |
|
| myocardial revascularization | Coronary Artery Bypass Surgery | versus No demonstrated result for efficacy | 8 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| MASS II, 2007 | CABG vs medical treatment | | | 5y death 0.64 [0.35; 1.16] | | BARI 2D, 2009 | CABG or PCI vs medical treatment | | | MI 0.87 [0.69; 1.09] stroke 0.92 [0.57; 1.50] death, MI, stroke 0.95 [0.82; 1.10] 5y death 0.98 [0.79; 1.20] | | VA, 1984 | CABG vs medical treatment | 7yr death 0.76 [0.59; 0.99] | | 5y death 0.78 [0.58; 1.06] 10 year death 0.89 [0.74; 1.08] | | ECSS (European), 1988 | CABG vs medical treatment | cardiac death 0.57 [0.41; 0.80] 5y death 0.45 [0.30; 0.68] 7yr death 0.64 [0.46; 0.88] | | noncardiovascular death 1.54 [0.64; 3.67] 10 year death 0.79 [0.62; 1.00] | | CASS, 1983 | CABG vs medical treatment | | | 5y death 0.63 [0.36; 1.07] 7yr death 0.81 [0.56; 1.18] 10 year death 0.87 [0.65; 1.15] | | Texas, 1977 | CABG vs medical treatment | | | 5y death 0.82 [0.39; 1.73] 7yr death 0.89 [0.50; 1.60] 10 year death 0.99 [0.64; 1.52] | | Oregon, 1979 | CABG vs medical treatment | | | 5y death 0.48 [0.15; 1.49] 7yr death 0.61 [0.26; 1.45] 10 year death 0.96 [0.51; 1.80] | | New zealand 1, 1981 | CABG vs medical treatment | | | 5y death 1.00 [0.41; 2.46] 7yr death 0.91 [0.42; 1.95] 10 year death 1.06 [0.61; 1.86] |
| Trial | Treatments | Patients | Method |
|---|
| MASS II, 2007 | coronary artery bypass graft (CABG) (n=203) vs. medical therapy (n=203) | multivessel
coronary artery disease with stable angina and preserved ventricular function. | open Parallel groups Sample size: 203/203 Primary endpoint: death, MI, or unstable angina requiring revasc FU duration: 5 years | | BARI 2D, 2009 | prompt revascularization with intensive medical therapy (n=1176) vs. intensive
medical therapy alone (n=1192) factorial design with 2nd comparison: insulin-sensitization or insulin-provision
therapy | patients with type 2 diabetes and heart disease | open Parallel groups Sample size: 1176/1192 Primary endpoint: death FU duration: 5.3 y | | VA, 1984 | coronary-artery bypass grafting (n=332) vs. medical treatment (n=354) | patients with stable angina | open Parallel groups Sample size: 332/354 Primary endpoint: FU duration: 7 y | | ECSS (European), 1988 | early coronary bypass surgery (n=394) vs. medical therapy (n=373) | men with midl or moderate angina pectoris of at least 3 months duration and an obstruction of 50% or more in at least 2 major coronary arteries in the absence of marked LV dysfunction | open Parallel groups Sample size: 394/373 Primary endpoint: FU duration: 12 y | | CASS, 1983 | surgical (n=390) vs. nonsurgical (n=390) | patients with stable ischemic heart disease | open Parallel groups Sample size: 390/390 Primary endpoint: FU duration: 5y | | Texas, 1977 | (n=56) vs. (n=60) | | Sample size: 56/60 Primary endpoint: FU duration: | | Oregon, 1979 | surgical treatment (n=51) vs. medical treatment (n=49) | patients with stable, disabling angina | Sample size: 51/49 Primary endpoint: FU duration: | | New zealand 1, 1981 | surgical (n=50) vs. nonsurgical (n=50) | men 60 years of age or younger who had recovered from a recurrent myocardial infarction | Sample size: 50/50 Primary endpoint: FU duration: 4.5 y |
|
| myocardial revascularization | drug-eluting stents | versus surgery No demonstrated result for efficacy PCI with drug-eluting stents inferior to CABG in terms of 5 year cardiovascular events in FREEDOM, 2012 PCI with drug-eluting stents inferior to CABG in terms of long term death in FREEDOM, 2012 PCI with drug-eluting stents inferior to CABG in terms of long term cardiovascular events in FREEDOM, 2012 | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| FREEDOM, 2012 | PCI with drug-eluting stents vs CABG | | 5 year cardiovascular events 1.36 [1.12; 1.65] long term death 1.36 [1.05; 1.77] long term cardiovascular events 1.39 [1.14; 1.68] | 5 year death 1.40 [0.99; 1.97] Death 1.5 to 2 years 1.08 [0.76; 1.53] Events 2 years 1.11 [0.87; 1.42] | | Hong, 2005 | PCI withdrug-eluting stents vs CABG | | | |
| Trial | Treatments | Patients | Method |
|---|
| FREEDOM, 2012 | percutaneous coronary stenting (n=953) vs. CABG (n=947) | patients with diabetes and multivessel coronary artery disease | open Parallel groups Sample size: 953/947 Primary endpoint: death, MI, stroke FU duration: 3.8 yrs (median) | | Hong, 2005 | drug-eluting stents (n=119) vs. invasive direct coronary artery bypass (MIDCAB) surgery (n=70) | proximal left anterior descending (LAD) coronary artery stenosis | open Parallel groups Sample size: 119/70 Primary endpoint: FU duration: 9 months |
|
| myocardial revascularization | PCI | versus medical treatment No demonstrated result for efficacy PCI with or without stent inferior to medical treatment in terms of PTCA in MASS II, 2007 PCI with or without stent inferior to medical treatment in terms of Cardiac death or MI in MASS II, 2007 PCI with or without stent inferior to medical treatment in terms of Death in ALKK, 2003 | 8 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| AVERT, 1995 | PCI with or without stent vs medical treatment | | | Death 0.93 [0.06; 14.69] non fatal MI 1.16 [0.32; 4.24] Fatal and non fatal MI 0.93 [0.24; 3.64] cardiac death 0.93 [0.06; 14.69] CABG 4.17 [0.91; 19.01] PTCA 1.08 [0.60; 1.96] Cardiac death or MI 1.11 [0.35; 3.57] | | COURAGE, 2007 | PCI with or without stent vs medical treatment | revascularization 0.65 [0.56; 0.75] | | Death 0.89 [0.67; 1.17] non fatal MI 1.11 [0.88; 1.38] Death or MI 1.03 [0.87; 1.23] cardiac death 0.91 [0.52; 1.60] Death, MI and stroke 1.03 [0.87; 1.22] | | MASS II, 2007 | PCI with or without stent vs medical treatment | | PTCA 4.46 [1.53; 12.94] Cardiac death or MI 1.90 [1.00; 3.62] | 1-year death 2.97 [0.82; 10.82] 1-year MI 1.58 [0.74; 3.41] Death 0.95 [0.56; 1.61] non fatal MI 0.73 [0.44; 1.22] cardiac death 0.95 [0.56; 1.61] CABG 0.58 [0.23; 1.44] | | Dakik, 1998 | PCI with or without stent vs medical treatment | | | Death 1.16 [0.08; 17.28] non fatal MI ∞ [NaN; ∞] cardiac death 1.10 [0.07; 16.43] CABG 0.00 [0.00; NaN] PTCA NaN [NaN; NaN] Cardiac death or MI 3.47 [0.39; 30.68] | | ALKK, 2003 | PCI with or without stent vs medical treatment | cardiac death 0.29 [0.10; 0.86] PTCA 0.41 [0.18; 0.89] Angina 0.30 [0.13; 0.74] | Death 0.36 [0.15; 0.88] | non fatal MI 0.84 [0.38; 1.89] CABG 0.25 [0.03; 2.24] Cardiac death or MI 0.55 [0.30; 1.00] | | Hambrecht, 2004 | PCI with or without stent vs medical treatment | | | Death NaN [NaN; NaN] non fatal MI ∞ [NaN; ∞] cardiac death NaN [NaN; NaN] CABG ∞ [NaN; ∞] PTCA 3.06 [0.88; 10.65] Cardiac death or MI ∞ [NaN; ∞] | | Bech, 2001 | PCI with or without stent vs medical treatment | | | Death 0.51 [0.09; 2.69] non fatal MI ∞ [NaN; ∞] cardiac death 0.51 [0.05; 5.48] CABG ∞ [NaN; ∞] PTCA 1.52 [0.56; 4.09] Cardiac death or MI 2.02 [0.38; 10.77] | | TIME, 2001 | PCI with or without stent vs medical treatment | | | |
| Trial | Treatments | Patients | Method |
|---|
| AVERT, 1995 | angioplasty (n=177) vs. atorvastatin at 80 mg per day (n=164) | Angina or asymptomatic, MI orunstable angina but not within 14 days,no triple vessel disease | open Parallel groups Sample size: 177/164 Primary endpoint: FU duration: 1.5y | | COURAGE, 2007 | PCI coupled with optimal medical therapy (n=1149) vs. optimal medical therapy aloneitm (n=1138) Drug-eluting stents were not approved
for clinical use until the final 6 months of the
study, so few patients received these intracoronary
devices | patients with stable coronary
artery disease | open Parallel groups Sample size: 1149/1138 Primary endpoint: death from any cause and nonfatal myocardial infarction FU duration: median 4.6 y | | MASS II, 2007 | PCI (n=205) vs. medical therapy (n=203) | patients with multivessel coronary artery disease with stable angina and preserved ventricular function | open Parallel groups Sample size: 205/203 Primary endpoint: FU duration: 5y | | Dakik, 1998 | PTCA (n=19) vs. intensive medical therapy (n=22) | stable survivors of AMI | open Parallel groups Sample size: 19/22 Primary endpoint: FU duration: 1y | | ALKK, 2003 | angioplasty (n=149) vs. medical therapy (n=151) | patients with single vessel disease of the infarct vessel and no or minor angina pectoris in the subacute phase (1 to 6 weeks) after an acute myocardial infarction | open Parallel groups Sample size: 149/151 Primary endpoint: death,reMI,reIntervention, CABG, severe AP FU duration: 4.7y | | Hambrecht, 2004 | PCI (n=50) vs. 12 months of exercise training (20 minutes of bicycle ergometry per day) (n=51) | male patients aged 70 years | open Parallel groups Sample size: 50/51 Primary endpoint: FU duration: 1y | | Bech, 2001 | PTCA (n=90) vs. deferral of PTCA (n=91) | patients with planned PTCA and no documented ischemia and with coronary pressure–derived fractional flow reserve >0.75 | open Parallel groups Sample size: 90/91 Primary endpoint: FU duration: 2y | | TIME, 2001 | coronary angiography and revascularisation (n=-9) vs. optimised medical therapy (n=-9) | patients aged 75 years or older with chronic angina of at least Canadian Cardiac Society class II despite at least two antianginal drugs | open Parallel groups Sample size: -9/-9 Primary endpoint: quality of life after 6 months FU duration: |
|
| myocardial revascularization | PTCA | versus medical treatment No demonstrated result for efficacy balloon angioplasty inferior to medical treatment in terms of PTCA in MASS, 1995 balloon angioplasty inferior to medical treatment in terms of Death in ACIP, 1997 balloon angioplasty inferior to medical treatment in terms of Composite endpoint in SWISSI II, 2007 balloon angioplasty inferior to medical treatment in terms of Death in SWISSI II, 2007 balloon angioplasty inferior to medical treatment in terms of non fatal MI in SWISSI II, 2007 | 8 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| RITA 2, 1997 | balloon angioplasty vs medical treatment | Fatal and non fatal MI 1.96 [1.01; 3.79] PTCA 0.63 [0.50; 0.80] | | Death 1.02 [0.68; 1.53] non fatal MI 1.42 [0.84; 2.39] cardiac death 0.85 [0.48; 1.52] CABG 1.04 [0.75; 1.43] Angina 0.94 [0.88; 1.01] Cardiac death or MI 1.07 [0.71; 1.60] | | ACME, 1992 | balloon angioplasty vs medical treatment | Angina 0.75 [0.56; 0.99] | | Death 1.09 [0.57; 2.08] non fatal MI 0.87 [0.30; 2.51] Fatal and non fatal MI 1.70 [0.42; 6.93] CABG 1.10 [0.53; 2.31] PTCA 0.93 [0.62; 1.39] Cardiac death or MI 1.78 [0.78; 4.07] | | Sievers, 1993 | balloon angioplasty vs medical treatment | | | Death 0.00 [0.00; NaN] non fatal MI ∞ [NaN; ∞] Fatal and non fatal MI 2.00 [0.19; 21.26] cardiac death 0.00 [0.00; NaN] CABG 1.00 [0.15; 6.79] PTCA 0.71 [0.25; 2.08] Angina 1.00 [0.51; 1.98] Cardiac death or MI 2.00 [0.19; 21.26] | | MASS, 1995 | balloon angioplasty vs medical treatment | Angina 0.29 [0.17; 0.47] | PTCA 5.25 [1.90; 14.53] | Composite endpoint 1.42 [0.73; 2.75] Death 1.00 [0.34; 2.95] non fatal MI 1.33 [0.31; 5.75] Fatal and non fatal MI 1.00 [0.14; 6.91] cardiac death 2.00 [0.38; 10.58] CABG 1.00 [0.40; 2.52] Cardiac death or MI 1.40 [0.47; 4.21] | | ACME 2 (Folland), 1997 | balloon angioplasty vs medical treatment | | | Death 0.88 [0.39; 1.99] non fatal MI 0.98 [0.34; 2.84] Fatal and non fatal MI 0.33 [0.07; 1.54] CABG 2.94 [0.32; 27.33] PTCA 1.35 [0.59; 3.07] Angina 0.74 [0.51; 1.05] Cardiac death or MI 0.98 [0.34; 2.84] | | ACIP, 1997 | balloon angioplasty vs medical treatment | | Death 0.19 [0.05; 0.81] | non fatal MI 0.74 [0.32; 1.74] | | INSPIRE, 2006 | balloon angioplasty vs medical treatment | | | Death 1.94 [0.18; 21.09] non fatal MI 0.69 [0.23; 2.11] cardiac death 1.94 [0.18; 21.09] | | SWISSI II, 2007 | balloon angioplasty vs medical treatment | revascularization 0.62 [0.42; 0.92] cardiac death 0.15 [0.05; 0.48] | Composite endpoint 0.44 [0.31; 0.63] Death 0.30 [0.13; 0.70] non fatal MI 0.30 [0.16; 0.55] | |
| Trial | Treatments | Patients | Method |
|---|
| RITA 2, 1997 | PTCA within 3 mo of the randomisation (n=504) vs. medical treatment (n=514) | Angina leading to admission within 90days, previous Q wave MI, no previousPTCA, no left main stem disease | open Parallel groups Sample size: 504/514 Primary endpoint: FU duration: 7y | | ACME, 1992 | PTCA within 3 days of randomization (n=105) vs. medical treatment (nitrates, beta-blockers, calcium blockers) (n=107) | Stable angina, history of angina, MIwithin 3 months, exercise test with STdepression >3 mm, no previous PTCA; Single or serial stenosis within sameartery 70% to 99% proximal twothirds | open Parallel groups Sample size: 105/107 Primary endpoint: FU duration: 5y | | Sievers, 1993 | PTCA (n=44) vs. medical treatment (n=44) | Previous nonQ wave MI, no angina indaily life, no previous Q wave MI | open Parallel groups Sample size: 44/44 Primary endpoint: FU duration: 2y | | MASS, 1995 | PTCA (n=72) vs. medical treatment (aspirin, nitrates, beta-blockers and calcium channel blocking (n=72) | Stable angina, no Q wave MI, no leftventricular dysfunction^¾„ | open Parallel groups Sample size: 72/72 Primary endpoint: FU duration: 5y | | ACME 2 (Folland), 1997 | PTCA
(n=51) vs. medical therapy (n=50) | Stable angina, history of angina, MIwithin 3 months, exercise test with STdepression >3 mm, no previous PTCA; Stenosis >70% proximal two thirds,no main artery stenosis >50%, no 3vessel disease | open Parallel groups Sample size: 51/50 Primary endpoint: FU duration: 5y | | ACIP, 1997 | revascularization by angioplasty or bypass surgery (n=192) vs. angina-guided drug therapy or angina plus ischemia-guided drug therapy (n=366) 46% of patients in revascularization group underwent CABG | clinically stable patients with angiographically documented coronary disease (50% stenosis in 1 major vessel or branch) suitable for revascularization | open Parallel groups Sample size: 192/366 Primary endpoint: none defined FU duration: 24 months | | INSPIRE, 2006 | coronary revascularization for suppressing scintigraphic ischemia (n=104) vs. intensive medical therapy strategy (n=101) | Stable survivors of MI, total perfusion defect size 20%, ischemic defect size 10% (by adenosine SPECT), EF 35%t | open Parallel groups Sample size: 104/101 Primary endpoint: FU duration: 60 months | | SWISSI II, 2007 | Percutaneous coronary intervention aimed at full revascularization (n=96) vs. intensive anti-ischemic drug therapy (n=105) | patients with
a recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel
coronary artery disease | open Parallel groups Sample size: 96/105 Primary endpoint: cardiac death, nonfatal MI, and/or symptom-driven revascularization FU duration: 10.2y |
|
| myocardial revascularization | PTCA | versus Surgery No demonstrated result for efficacy balloon angioplasty inferior to CABG in terms of CABG in first year in CABRI, 1995 balloon angioplasty inferior to CABG in terms of Angina (grade 2 or worse) in first year in CABRI, 1995 balloon angioplasty inferior to CABG in terms of Angina at 3 years in EAST, 1994 balloon angioplasty inferior to CABG in terms of Angina (grade 2 or worse) in first year in EAST, 1994 balloon angioplasty inferior to CABG in terms of CABG in first year in GABI, 1994 balloon angioplasty inferior to CABG in terms of CABG in first year in RITA, 1993 balloon angioplasty inferior to CABG in terms of Angina (grade 2 or worse) in first year in RITA, 1993 | 9 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| BARI, 1996 | balloon angioplasty vs CABG | | | Death 1.18 [0.93; 1.49] | | MASS, 1995 | balloon angioplasty vs CABG | | | Death 0.97 [0.06; 15.24] CABG in first year ∞ [NaN; ∞] Cardiac death or MI in first year 4.86 [0.58; 40.57] | | CABRI, 1995 | balloon angioplasty vs CABG | | CABG in first year 20.15 [7.45; 54.53] Angina (grade 2 or worse) in first year 1.42 [1.03; 1.98] | Death 1.42 [0.73; 2.77] Cardiac death or MI in first year 1.41 [0.89; 2.22] | | EAST, 1994 | balloon angioplasty vs CABG | | Angina at 3 years 1.70 [1.03; 2.81] Angina (grade 2 or worse) in first year 2.04 [1.18; 3.53] | Death 1.14 [0.54; 2.41] CABG in first year ∞ [NaN; ∞] Cardiac death or MI in first year 0.71 [0.44; 1.16] | | GABI, 1994 | balloon angioplasty vs CABG | | CABG in first year 15.56 [3.79; 63.96] | Death 0.43 [0.14; 1.38] Angina (grade 2 or worse) in first year 1.13 [0.77; 1.65] Cardiac death or MI in first year 0.54 [0.26; 1.14] | | Lausanne, 1994 | balloon angioplasty vs CABG | | | Death 3.88 [0.45; 33.83] CABG in first year 7.76 [1.00; 60.38] Cardiac death or MI in first year 2.91 [0.61; 13.91] | | RITA, 1993 | balloon angioplasty vs CABG | | CABG in first year 14.12 [6.97; 28.61] Angina (grade 2 or worse) in first year 1.94 [1.42; 2.65] | Death 0.91 [0.53; 1.56] Angina at 3 years 1.13 [0.86; 1.50] Cardiac death or MI in first year 1.08 [0.67; 1.73] | | ERACI, 1992 | balloon angioplasty vs CABG | | | Death 2.03 [0.53; 7.77] CABG in first year ∞ [NaN; ∞] Cardiac death or MI in first year 1.16 [0.45; 3.01] | | Toulouse, 1992 | balloon angioplasty vs CABG | | | Death 0.71 [0.24; 2.15] CABG in first year 7.00 [0.88; 55.53] Cardiac death or MI in first year 1.00 [0.34; 2.96] |
| Trial | Treatments | Patients | Method |
|---|
| BARI, 1996 | PTCA (n=915) vs. CABG (n=914) | Patients with multivessel disease | open Sample size: 915/914 Primary endpoint: FU duration: 5.4 y | | MASS, 1995 | percutaneous transluminal coronaryangioplasty (n=72) vs. mammary bypass surgery (n=70) | patients with stable angina,normal ventricular function and a proximal stenosis of the leftanterior descending coronary artery >80% | open Sample size: 72/70 Primary endpoint: FU duration: 3.2 y | | CABRI, 1995 | percutaneous transluminal coronary angioplasty (n=541) vs. coronary artery bypass grafting (n=513) | patients with symptomatic multivessel coronary disease | open Sample size: 541/513 Primary endpoint: FU duration: 1 y | | EAST, 1994 | transluminal coronary angioplasty (n=198) vs. coronary-artery bypass grafting (n=194) | patients with multivessels coronary artery disease | open Sample size: 198/194 Primary endpoint: FU duration: 3 y | | GABI, 1994 | Percutaneous transluminal coronary angioplasty (n=182) vs. coronary-artery bypass grafting (n=177) | patients with symptomatic multivessel coronary disease | open Sample size: 182/177 Primary endpoint: FU duration: 1 y | | Lausanne, 1994 | transluminal coronary angioplasty (n=68) vs. Coronary artery bypass grafting (n=66) | patients with isolated proximal left anterior descending artery stenosis, conserved left ventricular function, and documented ischaemia | open Sample size: 68/66 Primary endpoint: FU duration: 3.2 y | | RITA, 1993 | percutaneous transluminal coronary angioplasty (n=510) vs. coronary artery bypass surgery (n=501) | patients with one, two, or three diseased coronary arteries | open Sample size: 510/501 Primary endpoint: FU duration: 2.5 y (6.5y) | | ERACI, 1992 | Percutaneous transluminal coronary angioplasty (n=63) vs. coronary artery bypass grafting (n=64) | patients with multivessel disease and lesions suitable for either form of therapy | open Sample size: 63/64 Primary endpoint: FU duration: 3.8 y | | Toulouse, 1992 | PTCA (n=76) vs. CABG (n=76) | patients with multivessels coronary artery disease | open Sample size: 76/76 Primary endpoint: FU duration: 2.8 y |
|
| myocardial revascularization | sirolimus eluting stent | versus surgery No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Thiele, 2009 | PCI withsirolimus ES vs MIDCAB | | | |
| Trial | Treatments | Patients | Method |
|---|
| Thiele, 2009 | sirolimus-eluting stent (n=65) vs. MIDCAB surgery (n=65) | isolated LAD disease | open Parallel groups Sample size: 65/65 Primary endpoint: cardiac death, MI, and need for PCI FU duration: 12 months |
|
