| pathology | Demonstrated benefit and harm | k | | | |
|---|
| acute myocardial infarction | versus placebo or control No demonstrated result for efficacy captopril inferior to placebo in terms of Death in ISIS-4, 1995 | 19 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ISIS-4, 1995 | captopril vs placebo | | Death 0.94 [0.88; 0.99] | | | captopril vs placebo | | | | | SAVE, 1992 | captopril vs placebo | | | | | captopril vs placebo | | | | | captopril vs placebo | | | | | captopril vs placebo | | | | | captopril vs placebo | | | | | captopril vs placebo | | | | | captopril vs placebo | | | | | captopril or enalapril vs placebo | | | | | captopril vs placebo | | | | | captopril vs placebo | | | | | captopril vs placebo | | | | | captopril vs placebo | | | | | Bussmann, 1992 | captopril vs placebo | | | | | Di Pasquale, 1994 | captopril vs placebo | | | | | Di Pasquale, 1997 | captopril vs placebo | | | | | Galcera, 1993 | captopril vs placebo | | | | | Hargreaves, 1992 | captopril vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| ISIS-4, 1995 | captopril 6.25mg twice daily initialy titrated up to 50 mg twice daily (for 1 month) (n=29028) vs. placebo (n=29022) | Acute MI <24h of MI, no cardiogenic shock or persistent severe hypotension | double blind Factorial plan Sample size: 29028/29022 Primary endpoint: death FU duration: 1 month | | CCS-1, 1995 | captopril6.25 mg initial dose, 12.5 mg 2 h later, and then 12.5 mg three times daily for 28 days (n=13634) vs. placebo (n=0) | Acute MI <36h of MI | double blind Parallel groups Sample size: 13634/0 Primary endpoint: death FU duration: 1 month | | SAVE, 1992 | Captopril 12·5 mg initial dose, up to 25–50 mg three times daily (n=1115) vs. placebo (n=1116) | patient within 3–16 days of a MI, LVEF <40% | double blind Parallel groups Sample size: 1115/1116 Primary endpoint: Mortality from all causes FU duration: 3.5y | | Pfeffer, 1988 | Captopril (n=38) vs. placebo (n=0) | patient within 11-31 days after MI, LVEF<=45%, not in overt congestive heart failure | double blind Parallel groups Sample size: 38/0 Primary endpoint: hemodynamic function and left ventricular volume FU duration: 1 year | | Sogaard, 1994 | Captopril 50mg daily (n=58) vs. placebo (n=0) | patients with left ventricular (LV) dysfunction on day 7 after MI | double blind Parallel groups Sample size: 58/0 Primary endpoint: Ventricular arrhythmias FU duration: 6 months | | Sharpe, 1988 | Captopril 25 mg thrice a day (n=60) vs. placebo (n=0) | patients with symptomless left ventricular dysfunction (LVEF<45%) 1 week after a myocardial infarction without clinical evidence of heart failure | double blind Parallel groups Sample size: 60/0 Primary endpoint: left ventricular volumes FU duration: 1 year | | Mortarino, 1990 | Captopril 25 mg bid (n=10) vs. placebo (n=11) | patient with mild congestive heart failure after recent MI | double blind Parallel groups Sample size: 10/11 Primary endpoint: none FU duration: 2 months | | French, 1999 | captopril 6.25 mg, increasing to 50 mg t.d.s. (n=243) vs. placebo (n=250) | patients aged < or = 75 years with first infarctions, presenting within 4 h of symptom onset | double blind Parallel groups Sample size: 243/250 Primary endpoint: regional wall motion FU duration: 1 year | | CATS, 1996 | captopril 25 mg three times a day (n=149) vs. placebo (n=149) | patients with a first anterior myocardial infarction treated with intravenous streptokinase within 6h of onset of symptoms | double blind Parallel groups Sample size: 149/149 Primary endpoint: left ventricular volume index FU duration: 1 year | | PRACTICAL (captopril), 1994 | captopril 25 mg three times daily or enalapril 5 mg three times daily (n=150) vs. placebo (n=75) | patients with acute myocardial infarction within 24 hours of onset | double blind Parallel groups Sample size: 150/75 Primary endpoint: LV function FU duration: 1 year | | ECCE, 1997 | captopril titrated dose in order to preserve their blood pressure (n=104) vs. placebo (n=104) | patients with acute myocardial infarction | double blind Parallel groups Sample size: 104/104 Primary endpoint: exercise testing FU duration: 1 month | | Sharpe, 1991 | captopril 50 mg twice daily (n=100) vs. placebo (n=0) | patients with Q wave myocardial infarction, but without clinical heart failure 24-48h after onset of symptoms | double blind Parallel groups Sample size: 100/0 Primary endpoint: Left ventricular volumes FU duration: 3 months | | Ray, 1993 | captopril 25 mg three times a day (n=99) vs. placebo (n=0) | haemodynamically stable patients with acute myocardial infarction, selected on clinical grounds as being at risk of late ventricular dilatation | double blind Parallel groups Sample size: 99/0 Primary endpoint: none FU duration: 1 year | | Nabel, 1991 | intravenous followed by oral captopril (n=20) vs. placebo (n=18) | patients with myocardial infarction | double blind Parallel groups Sample size: 20/18 Primary endpoint: none FU duration: 3 months | | Bussmann, 1992 | slow intravenous bolus injection of 2.5 or 5.0 mg captopril followed by a continuous infusion of 1.5-2.0 mg/h for a period of 48 hours (n=22) vs. placebo (n=24) | patients with acute myocardial infarction | double blind Parallel groups Sample size: 22/24 Primary endpoint: QRS complexes FU duration: 48h | | Di Pasquale, 1994 | captopril, 6.25 mg, orally 15 min before thrombolysis (n=188) vs. placebo before thrombolysis (n=183) | patients with acute myocardial infarction , hospitalized within 4 h of the onset of symptoms | double blind Parallel groups Sample size: 188/183 Primary endpoint: not defined FU duration: 2h | | Di Pasquale, 1997 | captopril first dose 2-4 h after starting thrombolysis (the dose was then increased up to 25 mg every 8 h (n=31) vs. placebo (n=30) | patients hospitalized for suspected anterior AMI within 4 h from the onset of symptoms suitable for thrombolysis | double blind Parallel groups Sample size: 31/30 Primary endpoint: not defined FU duration: 12h | | Galcera, 1993 | captopril (n=21) vs. placebo (n=22) | patients with a first acute myocardial infarction and a pulmonary capillary pressure equal or above 17 mmHg | double blind Parallel groups Sample size: 21/22 Primary endpoint: left ventricular volume indexes FU duration: 14 days | | Hargreaves, 1992 | 12.5 mg of captopril three times daily (n=36) vs. placebo (n=36) | patients with acute myocardial infarction (systolic blood pressure > 90 mm Hg) within 24 hours of the start of pain | double blind Parallel groups Sample size: 36/36 Primary endpoint: none defined FU duration: 28 days |
|
| diabetes type 2 | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| UKPDS 38, 1998 | captopril or atenolol vs control | Stroke 0.58 [0.37; 0.90] microvascular events 0.65 [0.46; 0.91] | | All deaths 0.83 [0.65; 1.06] Fatal and nonfatal MI 0.80 [0.60; 1.05] |
| Trial | Treatments | Patients | Method |
|---|
| UKPDS 38, 1998 | tight control of blood pressure aiming at a BP <150/85 (with the use of captopril or atenolol as main treatment, other treatment were added if the control criteria were not met) (n=758) vs. less tight control aiming at a blood pressure of <180/105 (avoiding treatment with ACE inhibitors or beta-blockers) (n=390)
| hypertensive patients with type 2 diabetes
| open Parallel groups Sample size: 758/390 Primary endpoint: not unique (3) FU duration: 8.4y (median)
|
|
| diabetes type 2 | versus beta-blockers No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| UKPDS 39, 1998 | captopril vs atenolol | | | All deaths 1.14 [0.83; 1.55] Stroke 1.38 [0.74; 2.57] Fatal and nonfatal MI 1.19 [0.83; 1.69] microvascular events 1.28 [0.81; 2.03] |
| Trial | Treatments | Patients | Method |
|---|
| UKPDS 39, 1998 | captopril 25 mg/d aiming at a BP <150/85 (n=400) vs. atenolol 50mg/d aiming at a BP <150/85 (n=358) | hypertensive patients with type 2 diabetes | open Parallel groups Sample size: 400/358 Primary endpoint: not unique (3) FU duration: ND |
|
| diabetes type 2 | versus diuretic and/or beta-blocker No demonstrated result for efficacy captopril inferior to diuretic and/or beta-blockers in terms of Fatal and nonfatal MI in CAPP (diabetic subgroup), 1999 | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| CAPP (diabetic subgroup), 1999 | captopril vs diuretic and/or beta-blockers | All deaths 0.54 [0.31; 0.95] Cardiovascular events 0.59 [0.38; 0.91] | Fatal and nonfatal MI 0.38 [0.20; 0.73] | Cardiovascular death 0.48 [0.21; 1.10] Stroke 1.03 [0.57; 1.85] |
| Trial | Treatments | Patients | Method |
|---|
| CAPP (diabetic subgroup), 1999 | Captopril initial dose of 50 mg daily given in one or two doses (n=309) vs. thiazide diuretic or beta-blocker (n=263) | Patients aged 25-66 years with a measured diastolic blood pressure of 100 mm Hg or more on two occasions; subgroup of diabetic patients | open with blinded assessment Parallel groups Sample size: 309/263 Primary endpoint: CV events FU duration: 6.1 year |
|
| heart failure | versus placebo or control No demonstrated result for efficacy | 5 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| SAVE, 1992 | captopril vs placebo | | | | | captopril vs placebo | | | | | captopril vs placebo | | | | | captopril vs placebo | | | | | captopril vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| SAVE, 1992 | Captopril 12·5 mg initial dose, up to 25–50 mg three times daily (n=1115) vs. placebo (n=1116) | patient within 3–16 days of a MI, LVEF <40% | double blind Parallel groups Sample size: 1115/1116 Primary endpoint: Mortality from all causes FU duration: 3.5y | | Pfeffer, 1988 | Captopril (n=38) vs. placebo (n=0) | patient within 11-31 days after MI, LVEF<=45%, not in overt congestive heart failure | double blind Parallel groups Sample size: 38/0 Primary endpoint: hemodynamic function and left ventricular volume FU duration: 1 year | | Sogaard, 1994 | Captopril 50mg daily (n=58) vs. placebo (n=0) | patients with left ventricular (LV) dysfunction on day 7 after MI | double blind Parallel groups Sample size: 58/0 Primary endpoint: Ventricular arrhythmias FU duration: 6 months | | Sharpe, 1988 | Captopril 25 mg thrice a day (n=60) vs. placebo (n=0) | patients with symptomless left ventricular dysfunction (LVEF<45%) 1 week after a myocardial infarction without clinical evidence of heart failure | double blind Parallel groups Sample size: 60/0 Primary endpoint: left ventricular volumes FU duration: 1 year | | Mortarino, 1990 | Captopril 25 mg bid (n=10) vs. placebo (n=11) | patient with mild congestive heart failure after recent MI | double blind Parallel groups Sample size: 10/11 Primary endpoint: none FU duration: 2 months |
|
| heart failure | 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
|
|
| heart failure | 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 |
|
| hypertension | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| UKPDS 38, 1998 | captopril or atenolol vs control | Stroke 0.58 [0.37; 0.90] microvascular events 0.65 [0.46; 0.91] | | All deaths 0.83 [0.65; 1.06] Fatal and nonfatal MI 0.80 [0.60; 1.05] |
| Trial | Treatments | Patients | Method |
|---|
| UKPDS 38, 1998 | tight control of blood pressure aiming at a BP <150/85 (with the use of captopril or atenolol as main treatment, other treatment were added if the control criteria were not met) (n=758) vs. less tight control aiming at a blood pressure of <180/105 (avoiding treatment with ACE inhibitors or beta-blockers) (n=390)
| hypertensive patients with type 2 diabetes
| open Parallel groups Sample size: 758/390 Primary endpoint: not unique (3) FU duration: 8.4y (median)
|
|
| hypertension | versus ACEIs No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| VALIANT/Val+Cap, 2003 | Valsartan + captopril vs Captopril | | | all-cause mortality 0.99 [0.91; 1.07] cardiovascular mortality 1.00 [0.92; 1.09] stroke 0.87 [0.72; 1.06] MI 0.95 [0.87; 1.04] |
| Trial | Treatments | Patients | Method |
|---|
| VALIANT/Val+Cap, 2003 | Valsartan + captopril (n=4885) vs. Captopril (n=4909) | patients with myocardial infarction complicated by left ventricular systolic dysfunction, heart failure, or both | double-blind Parallel groups Sample size: 4885/4909 Primary endpoint: death from any cause FU duration: 2.1 y |
|
| hypertension | versus beta-blockers No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| UKPDS 39, 1998 | captopril vs atenolol | | | All deaths 1.14 [0.83; 1.55] Stroke 1.38 [0.74; 2.57] Fatal and nonfatal MI 1.19 [0.83; 1.69] microvascular events 1.28 [0.81; 2.03] |
| Trial | Treatments | Patients | Method |
|---|
| UKPDS 39, 1998 | captopril 25 mg/d aiming at a BP <150/85 (n=400) vs. atenolol 50mg/d aiming at a BP <150/85 (n=358) | hypertensive patients with type 2 diabetes | open Parallel groups Sample size: 400/358 Primary endpoint: not unique (3) FU duration: ND |
|
| hypertension | versus diuretic and/or beta-blocker No demonstrated result for efficacy captopril inferior to diuretic and/or beta-blockers in terms of Fatal and nonfatal MI in CAPP (diabetic subgroup), 1999 | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| CAPP (diabetic subgroup), 1999 | captopril vs diuretic and/or beta-blockers | All deaths 0.54 [0.31; 0.95] Cardiovascular events 0.59 [0.38; 0.91] | Fatal and nonfatal MI 0.38 [0.20; 0.73] | Cardiovascular death 0.48 [0.21; 1.10] Stroke 1.03 [0.57; 1.85] |
| Trial | Treatments | Patients | Method |
|---|
| CAPP (diabetic subgroup), 1999 | Captopril initial dose of 50 mg daily given in one or two doses (n=309) vs. thiazide diuretic or beta-blocker (n=263) | Patients aged 25-66 years with a measured diastolic blood pressure of 100 mm Hg or more on two occasions; subgroup of diabetic patients | open with blinded assessment Parallel groups Sample size: 309/263 Primary endpoint: CV events FU duration: 6.1 year |
|
| hypertension | versus diuretic or beta-blocker No demonstrated result for efficacy captopril inferior to diuretic or beta-blocker in terms of stroke (fatal & non fatal) in CAPPP, 1999 | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| UKPDS-HDS, 1998 | captopril vs diuretic or beta-blocker | | | microvascular disease 1.28 [0.81; 2.03] all cause death 1.14 [0.83; 1.55] coronary heart disease 1.19 [0.83; 1.69] cardiovascular death 1.34 [0.88; 2.05] fatal MI 1.31 [0.79; 2.15] heart failure 1.19 [0.51; 2.80] fatal stroke 0.72 [0.19; 2.65] stroke (fatal & non fatal) 1.11 [0.59; 2.06] Peripheral arterial disease 1.49 [0.36; 6.20] end stage renal disease 0.90 [0.23; 3.55] | | CAPPP, 1999 | captopril vs diuretic or beta-blocker | | stroke (fatal & non fatal) 1.28 [1.03; 1.58] | all cause death 0.97 [0.79; 1.18] coronary heart disease 0.96 [0.78; 1.18] cardiovascular death 0.80 [0.59; 1.08] heart failure 1.14 [0.82; 1.58] Major cardiovascular events 1.08 [0.94; 1.24] |
| Trial | Treatments | Patients | Method |
|---|
| UKPDS-HDS, 1998 | captopril started at 25mg twice daily up to 50 mg twice dialy (target blood pressure of <150/<85 mmHG) (n=400) vs. atenolol started at 50mg daily up to 100mg if required(target blood pressure of <150/<85 mmHG) (n=358) | HBP+DM | Open Parallel groups Sample size: 400/358 Primary endpoint: FU duration: 8·4 y | | CAPPP, 1999 | captopril 50mg/d (n=5492) vs. beta-blocker (not specified) or diuretic (not specified) (n=5493) | Patients aged 25–66 years with a measured diastolic bloodpressure of 100 mm Hg or more on two occasions | Open Parallel groups Sample size: 5492/5493 Primary endpoint: fatal and non-fatal myocardial infarction, stroke, and other cardiovascular deaths FU duration: 6.1 y |
|
