| pathology | Benefit (demonstrated or suggested) and harm | | | |
|---|
| acute myocardial infarction | All results are NS for efficacy | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| AIRE, 1993 | vs placebo | | | | | Wagner, 2002 | vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| AIRE, 1993 | Ramipril 2·5 mg twice daily initial dose, up to 5 mg twice daily for at least 6 months (n=1004) vs. placebo (n=992) | patient within 3–10 days of a MI,with clinical evidence of heart failure | Double blind Parallel groups Sample size: 1004/992 Primary endpoint: FU duration: 1.25 y | | Wagner, 2002 | 2.5 mg ramipril orally prior to thrombolysis and 12 h later (n=51) vs. placebo (n=48) | patients with acute myocardial infarction | double blind Parallel groups Sample size: 51/48 Primary endpoint: PAI-1 plasma levels FU duration: 7 days |
|
| diabetes type 2 | All results are NS for efficacy inferior to placebo in terms of normoglycemia in DREAM ramipril, 2006 inferior to placebo in terms of heart failuer (fatal and non fatal) in DIABHYCAR, 2004 inferior to placebo in terms of Doubling of serum creatinine in DIABHYCAR, 2004 | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| DREAM ramipril, 2006 | vs placebo | | normoglycemia 1.11 [1.04; 1.19] | death 0.98 [0.60; 1.60] CV death 1.21 [0.52; 2.80] cardiovasculaire events 1.07 [0.76; 1.51] diabetes 0.93 [0.82; 1.04] | | DIABHYCAR, 2004 | vs placebo | | heart failuer (fatal and non fatal) 28.63 [9.07; 90.44] Doubling of serum creatinine 24.26 [5.90; 99.69] | new or worsening nephropathy 0.40 [0.13; 1.29] peripheral arterial disease 1.09 [0.64; 1.85] All deaths 1.04 [0.90; 1.20] Cardiovascular death 1.07 [0.85; 1.35] non fatal stroke 1.07 [0.80; 1.44] non fatal MI 0.89 [0.62; 1.29] Stroke 1.03 [0.80; 1.32] Fatal and nonfatal MI 0.79 [0.57; 1.10] Cardiovascular events 0.97 [0.85; 1.11] new or worsening retinopathy ∞ [NaN; ∞] visual deterioration ∞ [NaN; ∞] renal death ∞ [NaN; ∞] | | DREAM, 2008 | vs placebo | | | new or worsening nephropathy 0.98 [0.85; 1.12] All deaths 0.98 [0.60; 1.60] Cardiovascular death 1.21 [0.52; 2.80] Stroke 0.50 [0.15; 1.67] Fatal and nonfatal MI 1.28 [0.58; 2.82] Cardiovascular events 0.94 [0.56; 1.58] |
| Trial | Treatments | Patients | Method |
|---|
| DREAM ramipril, 2006 | ramipril up to 15 mg daily (n=2623) vs. placebo (n=2646) factorial design with rosiglitazone | patients with impaired fasting glucose or impaired glucose tolerance, or both, and no previous cardiovascular disease | double blind Parallel groups Sample size: 2623/2646 Primary endpoint: diabetes or death FU duration: 3 y (median) | | DIABHYCAR, 2004 | ramipril 1.25 mg/day (n=2443) vs. placebo (n=2469) | patients with type 2 diabetes who have microalbuminuria or proteinuria | double-blind Parallel groups Sample size: 2443/2469 Primary endpoint: cardiovascular death, non-fatal MI, stroke, HF, end-stage renal failure FU duration: median 4 years conducted mostly
by general practitioners in 16 countries | | DREAM, 2008 | ramipril(up to 15 mg per day) (n=2623) vs. placebo (n=2646) factorial design with 2nd randomization between rosiglytazone vs placebo | people aged >=30 years, with
Impaired glucose tolerance and/or impaired fasting glucose without known CVD or renal insufficiency | open Factorial plan Sample size: 2623/2646 Primary endpoint: development of diabetes or death FU duration: 3 years |
|
| diabetic kidney disease | All results are NS for efficacy inferior to placebo in terms of heart failuer (fatal and non fatal) in DIABHYCAR, 2004 inferior to placebo in terms of Doubling of serum creatinine in DIABHYCAR, 2004 | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| DIABHYCAR, 2004 | vs placebo | | heart failuer (fatal and non fatal) 28.63 [9.07; 90.44] Doubling of serum creatinine 24.26 [5.90; 99.69] | new or worsening nephropathy 0.40 [0.13; 1.29] peripheral arterial disease 1.09 [0.64; 1.85] All deaths 1.04 [0.90; 1.20] Cardiovascular death 1.07 [0.85; 1.35] non fatal stroke 1.07 [0.80; 1.44] non fatal MI 0.89 [0.62; 1.29] Stroke 1.03 [0.80; 1.32] Fatal and nonfatal MI 0.79 [0.57; 1.10] Cardiovascular events 0.97 [0.85; 1.11] new or worsening retinopathy ∞ [NaN; ∞] visual deterioration ∞ [NaN; ∞] renal death ∞ [NaN; ∞] |
| Trial | Treatments | Patients | Method |
|---|
| DIABHYCAR, 2004 | ramipril 1.25 mg/day (n=2443) vs. placebo (n=2469) | patients with type 2 diabetes who have microalbuminuria or proteinuria | double-blind Parallel groups Sample size: 2443/2469 Primary endpoint: cardiovascular death, non-fatal MI, stroke, HF, end-stage renal failure FU duration: median 4 years conducted mostly
by general practitioners in 16 countries |
|
| heart failure | All results are NS for efficacy | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Swedberg, 1991 | vs control | | | all cause death or hospitalisation 0.44 [0.19; 1.03] | | Maass-a, 1991 | vs control | | | all cause death or hospitalisation 1.03 [0.33; 3.25] | | Gordon, 1991 | vs control | all cause death or hospitalisation 0.21 [0.05; 0.93] | | | | Maass-b, 1991 | vs control | | | all cause death or hospitalisation 0.61 [0.28; 1.34] | | Maass-c, 1991 | vs control | | | all cause death or hospitalisation 0.68 [0.12; 3.89] | | Lemarie, 1992 | vs control | | | all cause death or hospitalisation 0.77 [0.18; 3.23] | | AIRE, 1993 | vs control | | | | | vs control | | | |
| 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 | | AIRE, 1993 | Ramipril 2·5 mg twice daily initial dose, up to 5 mg twice daily for at least 6 months (n=1004) vs. placebo (n=992) | patient within 3–10 days of a MI,with clinical evidence of heart failure | Double blind Parallel groups Sample size: 1004/992 Primary endpoint: FU duration: 1.25 y | | 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 |
|
| hypertension | All results are NS for efficacy | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| AASK (ramipril vs metoprolol), 2002 | vs amlodipine | | | all cause death 0.77 [0.48; 1.23] | | AASK (ramipril vs amlodipine), 2002 | vs amlodipine | | | all cause death 1.11 [0.59; 2.09] cardiovascular death 0.50 [0.07; 3.51] Major cardiovascular events 1.37 [0.44; 4.25] | | ONTARGET/Tel+Ram, 2008 | vs amlodipine | | | all-cause mortality 1.06 [0.98; 1.15] cardiovascular mortality 1.04 [0.93; 1.16] stroke 0.93 [0.81; 1.07] MI 1.07 [0.94; 1.22] | | Li et al, 2003 | vs amlodipine | | | all cause mortality 1.00 [0.22; 4.56] Cardiovascular mortality 1.00 [0.15; 6.64] cardiovascular event 1.00 [0.32; 3.10] |
| Trial | Treatments | Patients | Method |
|---|
| AASK (ramipril vs metoprolol), 2002 | ramipril 2.5-10 mg/d (n=436) vs. metoprolol 50-200 mg/d (n=441) | African Americans aged 18 to 70 years with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m(2)) | Double blind Parallel groups Sample size: 436/441 Primary endpoint: glomerular filtration rate (GFR) decline FU duration: 4·1 y | | AASK (ramipril vs amlodipine), 2002 | ramipril 2.5-10 mg/d (n=436) vs. amlodipine 5-10 mg/d (n=217) | African Americans aged 18 to 70 years with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m(2)) | Double blind Parallel groups Sample size: 436/217 Primary endpoint: Rate of change in GFR FU duration: 3·0 y | | ONTARGET/Tel+Ram, 2008 | Telmisartan + ramipril (n=8502) vs. Ramipril (n=8576) | patients with vascular disease or high-risk diabetes | double-blind Parallel groups Sample size: 8502/8576 Primary endpoint: Cv events or hospitalization FU duration: 4.7 y | | Li et al, 2003 | Ramipril 5 mg/day (n=30) vs. Conventional treatment (n=30) | patients with end-stage renal failure treated with peritoneal dialysis | open Sample size: 30/30 Primary endpoint: FU duration: 12 months |
|
| impaired fasting glucose | All results are NS for efficacy inferior to placebo in terms of normoglycemia in DREAM ramipril, 2006 | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| DREAM ramipril, 2006 | vs placebo | | normoglycemia 1.11 [1.04; 1.19] | death 0.98 [0.60; 1.60] CV death 1.21 [0.52; 2.80] cardiovasculaire events 1.07 [0.76; 1.51] diabetes 0.93 [0.82; 1.04] |
| Trial | Treatments | Patients | Method |
|---|
| DREAM ramipril, 2006 | ramipril up to 15 mg daily (n=2623) vs. placebo (n=2646) factorial design with rosiglitazone | patients with impaired fasting glucose or impaired glucose tolerance, or both, and no previous cardiovascular disease | double blind Parallel groups Sample size: 2623/2646 Primary endpoint: diabetes or death FU duration: 3 y (median) |
|
| miscellaneous | All results are NS for efficacy inferior to telmisartan in terms of Insuffisance rénale in ONTARGET (association vs ramipril), 2008 inferior to telmisartan in terms of hypotension in ONTARGET (association vs ramipril), 2008 inferior to telmisartan in terms of Arrêt pour effet secondaire in ONTARGET (association vs ramipril), 2008 inferior to telmisartan in terms of Insuffisance rénale in ONTARGET (association vs telmisartan), 2008 inferior to telmisartan in terms of Toux in ONTARGET (association vs telmisartan), 2008 inferior to telmisartan in terms of hypotension in ONTARGET (association vs telmisartan), 2008 inferior to telmisartan in terms of Arrêt pour effet secondaire in ONTARGET (association vs telmisartan), 2008 | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ONTARGET (association vs ramipril), 2008 | vs telmisartan | | Insuffisance rénale 1.58 [1.14; 2.18] hypotension 2.75 [2.28; 3.31] Arrêt pour effet secondaire 1.20 [1.14; 1.26] | Crit principaux 0.99 [0.93; 1.06] nouveau diabète 0.89 [0.77; 1.03] Mortalité totale 1.06 [0.98; 1.15] Ev. coronariens 1.07 [0.94; 1.22] Décès cardiovasculaires 1.04 [0.93; 1.16] revascularisation 1.04 [0.96; 1.11] AVC mortels et non mortels 0.93 [0.81; 1.07] Toux 1.10 [0.96; 1.26] Ev. cardiovasculaires 1.00 [0.93; 1.08] Angiodème 0.73 [0.40; 1.33] | | ONTARGET (association vs telmisartan), 2008 | vs telmisartan | nouveau diabète 0.81 [0.70; 0.94] | Insuffisance rénale 1.39 [1.02; 1.89] Toux 4.23 [3.38; 5.30] hypotension 1.78 [1.52; 2.09] Arrêt pour effet secondaire 1.28 [1.21; 1.34] | Crit principaux 0.98 [0.91; 1.05] Mortalité totale 1.08 [1.00; 1.17] Ev. coronariens 1.00 [0.88; 1.14] Décès cardiovasculaires 1.04 [0.93; 1.16] revascularisation 1.01 [0.95; 1.09] AVC mortels et non mortels 1.02 [0.88; 1.17] Ev. cardiovasculaires 1.01 [0.94; 1.09] Angiodème 1.81 [0.84; 3.92] |
| Trial | Treatments | Patients | Method |
|---|
| ONTARGET (association vs ramipril), 2008 | telmisartan 80mg + ramipril 10mg daily (n=8502) vs. ramipril 10 mg daily
(n=8576)
| patients patients with coronary, peripheral, or cerebrovascular disease or diabetes with end-organ damage
| double blind Parallel groups Sample size: 8502/8576 Primary endpoint: cardiovascular events or hospitalization for HF FU duration: 4.7y
| | ONTARGET (association vs telmisartan), 2008 | telmisartan 80mg + ramipril 10mg daily
(n=8502) vs. telmisartan 80 mg daily (n=8542)
| patients patients with coronary, peripheral, or cerebrovascular disease or diabetes with end-organ damage
| double blind Parallel groups Sample size: 8502/8542 Primary endpoint: cardiovascular events or hospitalization for HF FU duration: 4.7y
|
|
| patients at high risk for cardiovascular events | All results are NS for efficacy inferior to telmisartan in terms of Toux in HOPE, 2000 inferior to telmisartan in terms of Angiodème in HOPE, 2000 inferior to telmisartan in terms of Insuffisance rénale in ONTARGET (association vs ramipril), 2008 inferior to telmisartan in terms of hypotension in ONTARGET (association vs ramipril), 2008 inferior to telmisartan in terms of Arrêt pour effet secondaire in ONTARGET (association vs ramipril), 2008 inferior to telmisartan in terms of Insuffisance rénale in ONTARGET (association vs telmisartan), 2008 inferior to telmisartan in terms of Toux in ONTARGET (association vs telmisartan), 2008 inferior to telmisartan in terms of hypotension in ONTARGET (association vs telmisartan), 2008 inferior to telmisartan in terms of Arrêt pour effet secondaire in ONTARGET (association vs telmisartan), 2008 | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| HOPE, 2000 | vs telmisartan | Crit principaux 0.79 [0.72; 0.87] nouveau diabète 0.66 [0.52; 0.84] Mortalité totale 0.85 [0.76; 0.95] Décès cardiovasculaires 0.75 [0.65; 0.87] revascularisation 0.87 [0.80; 0.95] Infarctus non mortel 0.81 [0.72; 0.91] AVC mortels et non mortels 0.69 [0.57; 0.84] Ev. cardiovasculaires 0.79 [0.72; 0.87] HOPE endpoint 0.79 [0.72; 0.87] | Toux 4.01 [3.17; 5.06] Angiodème 2.43 [1.01; 5.86] | hypotension 1.26 [0.92; 1.72] Arrêt pour effet secondaire 1.06 [0.99; 1.13] | | ONTARGET (association vs ramipril), 2008 | vs telmisartan | | Insuffisance rénale 1.58 [1.14; 2.18] hypotension 2.75 [2.28; 3.31] Arrêt pour effet secondaire 1.20 [1.14; 1.26] | Crit principaux 0.99 [0.93; 1.06] nouveau diabète 0.89 [0.77; 1.03] Mortalité totale 1.06 [0.98; 1.15] Ev. coronariens 1.07 [0.94; 1.22] Décès cardiovasculaires 1.04 [0.93; 1.16] revascularisation 1.04 [0.96; 1.11] AVC mortels et non mortels 0.93 [0.81; 1.07] Toux 1.10 [0.96; 1.26] Ev. cardiovasculaires 1.00 [0.93; 1.08] Angiodème 0.73 [0.40; 1.33] | | ONTARGET (association vs telmisartan), 2008 | vs telmisartan | nouveau diabète 0.81 [0.70; 0.94] | Insuffisance rénale 1.39 [1.02; 1.89] Toux 4.23 [3.38; 5.30] hypotension 1.78 [1.52; 2.09] Arrêt pour effet secondaire 1.28 [1.21; 1.34] | Crit principaux 0.98 [0.91; 1.05] Mortalité totale 1.08 [1.00; 1.17] Ev. coronariens 1.00 [0.88; 1.14] Décès cardiovasculaires 1.04 [0.93; 1.16] revascularisation 1.01 [0.95; 1.09] AVC mortels et non mortels 1.02 [0.88; 1.17] Ev. cardiovasculaires 1.01 [0.94; 1.09] Angiodème 1.81 [0.84; 3.92] |
| Trial | Treatments | Patients | Method |
|---|
| HOPE, 2000 | ramipril 10 mg once per day orally (n=4645) vs. placebo (n=4652) | high-risk patients (55 years of age or older) with evidence of vascular disease or diabetes plus one other cardiovascular risk factor and who were not known to have a low ejection fraction or heart failure | double blind Parallel groups Sample size: 4645/4652 Primary endpoint: FU duration: 5 y | | ONTARGET (association vs ramipril), 2008 | telmisartan 80mg + ramipril 10mg daily (n=8502) vs. ramipril 10 mg daily
(n=8576)
| patients patients with coronary, peripheral, or cerebrovascular disease or diabetes with end-organ damage
| double blind Parallel groups Sample size: 8502/8576 Primary endpoint: cardiovascular events or hospitalization for HF FU duration: 4.7y
| | ONTARGET (association vs telmisartan), 2008 | telmisartan 80mg + ramipril 10mg daily
(n=8502) vs. telmisartan 80 mg daily (n=8542)
| patients patients with coronary, peripheral, or cerebrovascular disease or diabetes with end-organ damage
| double blind Parallel groups Sample size: 8502/8542 Primary endpoint: cardiovascular events or hospitalization for HF FU duration: 4.7y
|
|
