Table 1.
Characteristics of Randomized Clinical Trials of Antihypertensive Medications Included in the Meta-analysis (N = 25)a
| Trialb | Treatment Regimen | Participant Population | Duration of Follow-up, Mean (Range), Mo | ||
|---|---|---|---|---|---|
| Medication | Drug Class | Dose/Titration | |||
| MIS,22 1975 | Practolol | β-Blocker | 100 mg/d | 7–28 d post-MI | 14 (1–36) |
| MPI,23 1980 | Propranolol | β-Blocker | 40 mg ×3/d | 2–14 d post-MI (anterior infarction) | 5.6 (1–9) |
| BHAT,24 1982 | Propranolol | β-Blocker | 180 mg/d or 240 mg/d | 5–21 d post-MI | 25.1 (1–36) |
| ASPS,25 1983 | Pindolol | β-Blocker | 15 mg/d | 0–21 d post-MI (with electrical and/or mechanical complications) | 24 (1–24) |
| CONSENSUS II,26,27 1992 | Enalapril | ACEI | 20 mg/d | Presented within 24 h of onset of acute MI | 6 (1–20)c |
| SOLVD,28–31 1995 | Enalapril | ACEI | 2.5 or 5 mg ×2/d titrated to 10 mg ×2/d | CHF and LVEF ≤35% | 40 (15–62)d |
| USCHF,32 1996 | Carvedilol | β-Blocker | 12.5 mg ×2/d increased to 25 or 50 mg ×2/d | LVEF ≤35%, not receiving CCB, α- or β-adrenergic agonists or antagonists, or class IC or III antiarrhythmic agents | 6.5 (0–15)e |
| TRACE,33,34 1997 | Trandolapril | ACEI | 1 mg, titrated to 4 mg/d | LVEF ≤35%, 3–7 d post-MI | 26 (24–50) |
| AIRE,35,36 1999 | Ramipril | ACEI | 1.25, 2.5, or 5.0 mg ×2/d | Transient or persistent CHF, 2–9 d post-MI | 15 (6–20) |
| SMILE,37–39 1999 | Zofenopril calcium | ACEI | 7.5 mg ×2/d titrated to 30 mg/d | Presented within 24 h of onset of MI | 1.5 (0–1.5)f |
| MERIT-HF,40 2000 | Metoprolol CR/XL | β-Blocker | 25 or 12.5 mg/d to 200 mg | Symptomatic CHF for at least 3 mo, LVEF ≤40% | 12 (0–18) |
| CCS-1,41,42 2001 | Captopril | ACEI | 6.25 mg initial dose + 12.5 mg 2 h later, 12.5 mg ×3/d thereafter | Post-MI (acute MI in past 36 h) | 23.4 (6.5–40.3) |
| HOPE,43–46 2001 | Ramipril | ACEI | 2.5 mg initial dose progressively increased to 10 mg/d | History of CAD, stroke or PAD, or diabetes plus 1 additional risk factor | 54 (0–60) |
| ABCD,14,47 2002 | Nisoldipine or enalapril | CCB or ACEI | Nisoldipine 10 mg titrated to 60 mg/d or enalapril 5 mg/d titrated to 40 mg/d | Type 2 diabetes, DBP 80–89 mm Hg, not receiving antihypertensive medications | 63.6 (0–63.6) |
| CAMELOT,12 2004 | Amlodipine | CCB | 10 mg/d | LVEF ≥40%, CAD >20% stenosis by coronary angiography, and DBP <100 mm Hg | 24 (0–24) |
| COPERNICUS,48,49 2004 | Carvedilol | β-Blocker | 3.125 mg titrated to 25 mg ×2/d | LVEF <25% despite conventional therapies, dyspnea or fatigue at rest or with minimal exertion | 10.4 (0–28.7) |
| DIABHYCAR,50 2004 | Ramipril | ACEI | 1.25 mg/d | Type 2 diabetes, persistent microalbuminuria or proteinuria, serum creatinine ≤150 μmol/L, no MI in past 3 mo | 47 (36–72)e |
| PEACE,51–53 2004 | Trandolapril | ACEI | 2 mg/d increased to 4 mg/d | History of major CVD (if MI, at least 3 mo prior), LVEF >40% | 57.6 (0–84)e |
| SAVE,54,55 2004 | Captopril | ACEI | 12.5 mg titrated to target dose of 25 mg ×3/d, maximum 50 mg ×3/d | 3–16 d post-MI with LVEF ≤40% | 42 (24–60) |
| PROGRESS,56–58 2006 | Perindopril + indapamide | ACEI +diuretic | 4 mg perindopril + 2.5 mg indapamide daily (2.0 mg indapamide in Japan) | History of stroke or TIA within previous 5 y | 46.8 (0–54) |
| ADVANCE,59,60 2007 | Perindopril + indapamide | ACEI + diuretic | 2 mg/d perindopril + 0.625 mg indapamide; 4mg/d perindopril + 1.25 mg/d indapamide after 3 mo | Type 2 diabetes, ≥1 CVD risk factor, or history of microvascular or macrovascular disease | 51.6 (0–60) |
| PRoFESS,61,62 2008 | Temisartan | ARB | 80 mg/d | Stroke within previous 90 d if ≥55 y; stroke within previous 120 d if 50–54 y | 30 (18–52) |
| TRANSCEND,15 2008 | Temisartan | ARB | 80 mg/d | History of CAD, PVD, stroke, or diabetes with end-organ damage; intolerance to ACEIs | 56 (IQR, 51–64)e |
| EUROPA,13,63,64 2009 | Perindopril | ACEI | 8 mg/d | Documented CAD (MI >3 mo prior to enrollment) in men or women, history of angina, and confirmed ischemia on stress testing in men | 50.4 (0–60) |
| PATS,65 2009 | Indapamide | Diuretic | 2.5 mg/d | History of stroke or TIA (qualifying cerebrovascular event ≥4 weeks prior to enrollment) | 24 (0–45) |
Abbreviations: ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CAD, coronary artery disease; CCB, calcium channel blocker; CHF, congestive heart failure; CVD, cardiovascular disease; DBP, diastolic blood pressure; IQR, interquartile range; LVEF, left ventricular ejection fraction; MI, myocardial infarction; PAD, peripheral artery disease; PVD, peripheral vascular disease; TIA, transient ischemic attack.
All trials were double-blinded with the exception of the ABCD Normotensive Trial, which was single-blinded. Placebo control was used in all studies.
ABCD indicates Appropriate Blood Pressure Control in Diabetes–Normotensive Study; ADVANCE, Action in Diabetes and Vascular Disease: PreterAx and Diamicro N-MR Controlled Evaluation; AIRE, Acute Infarction Ramipril Efficacy; ASPS, Australian and Swedish Pindolol Study; BHAT, β-Blocker Heart Attack Trial Research Group; CAMELOT, Comparison of Amlodipine vs Enalapril to Limit Occurances of Thrombosis; CCS-1, Chinese Cardiac Study; CONSENSUS II, Cooperative New Scandinavian Enalapril Survival Study II; COPERNI-CUS, Carvedilol Prospective Randomized Cumulative Survival; DIABHYCAR, Noninsulin-Dependent Diabetes, Hypertension, Microalbuminuria or Proteinuria, Cardiovascular Events, and Ramipril Study; EUROPA, European trial on Reduction of Cardiac Events With Perindopril in Patients With Stable Coronary Artery Disease: HOPE, Heart Outcomes Prevention Evaluation; MERIT-HF, Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure; MIS, Multicenter International Study; MPI, Multicenter Post-Infarction Study; PATS, Post-Stroke Antihypertensive Treatment Study; PEACE, Prevention of Events With Angiotensin Converting Enzyme Inhibition Trial; PRoFESS, Prevention Regimen for Effectively Avoiding Second Strokes; PROGRESS, Perindopril Protection Against Recurrent Stroke Study; SAVE, Survival and Ventricular Enlargement Trial; SMILE, Survival of Myocardial Infarction Long-term Evaluation Study; SOLVD, Studies of Left Ventricular Dysfunction; TRACE, Trandolapril Cardiac Event Study; TRANSCEND, Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease; USCHF, US Carvedilol Heart Failure Study Group.
Patients (N=2952) underwent follow-up for 180 days, observation period ranged from 41 to 180 days.26
Mean follow-up time was 37.4 (range, 14.6–62.0) months and 41.4 (range, 22–55) months for the SOLVD Prevention and Treatment trials, respectively. Participants from both trials were included in the analysis of nonhypertensive participants.
Median follow-up time reported.
Double-blind treatment period was 6 weeks; maintenance treatment using conventional therapy was continued for 48 additional weeks. Six-week outcomes are evaluated in this meta-analysis.37