ArticlesCardiovascular protection and blood pressure reduction: a meta-analysis
Introduction
Lifetime risk of hypertension is about 20%. Several trials have been done to find the best possible protection against the cardiovascular complications of this widespread condition. Various drugs were tested to see whether their mode of action or ancillary properties could offer benefit beyond their effect of lowering blood pressure.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 In normotensive and hypertensive high-risk patients in the HOPE study,7 the angiotensin-converting enzyme (ACE) inhibitor ramipril significantly reduced rates of death, stroke, and myocardial infarction compared with placebo. In hypertensive patients enrolled in ALLHAT,10 fewer cardiovascular events happened during treatment with chlorthalidone than with the α-blocker doxazosin. However, in both studies,7, 10 systolic pressure was 2–3 mm Hg lower in the group with the best outcome, which could have been sufficient to explain the results.17, 18, 19 Two quantitative overviews20, 21 reached opposite conclusions with respect to cardiovascular protection of calcium-channel blockers compared with diuretics or β-blockers. However, neither of these overviews20, 21 specifically assessed blood pressure differences between randomised groups in relation to heterogeneity among trials, or included α-blockers in the group of newer drugs.
We investigated whether pharmacological properties of antihypertensive drugs or blood pressure reduction explained cardiovascular outcome. We focused on systolic pressure because, in middle-aged and older patients, systolic pressure is a better predictor of cardiovascular risk than diastolic pressure,22 and systolic pressure can be measured more reliably than diastolic pressure.23 First, we assessed whether differences in achieved systolic pressure between randomised groups led to heterogeneity among outcome trials of old versus new classes of antihypertensive drugs. Second, we used metaregression to measure to what extent blood pressure reduction accounts for results of outcome trials.
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Trials
We searched for outcome trials that tested drugs to lower blood pressure in normotensive or hypertensive patients who did not have overt heart failure at enrolment. Other inclusion criteria were a randomised controlled design, publication in a peer-reviewed journal, inclusion of patients with hypertension, assessment of blood pressure and cardiovascular events, follow-up of 2 years or longer, and sample size of 100 or more. Outcome trials of drugs to lower blood pressure were identified from
References (69)
- et al.
Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial
Lancet
(1999) - et al.
Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity in the Swedish Trial in Old Patients with Hypertension-2 study
Lancet
(1999) - et al.
Morbidity and mortality in patients randomised to double-blind treatment with long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS Study: Intervention as a Goal in Hypertensive Treatment (INSIGHT)
Lancet
(2000) - et al.
Randomised trial of effects of calcium antagonists compared with diuretics and β-blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study
Lancet
(2000) - et al.
Angiotensin-converting enzyme inhibition as anti-atherosclerotic therapy: no answer yet
Am J Cardiol
(1999) - et al.
Randomized, placebo-controlled trial of the angiotensin-converting enzyme inhibitor, ramipril, in patients with coronary or other occlusive arterial disease
J Am Coll Cardiol
(2000) - et al.
Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials
Lancet
(2000) - et al.
Health outcomes associated with calcium antagonists compared with other first-line antihypertensive therapies: a meta-analaysis of randomised controlled trials
Lancet
(2000) - et al.
Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial
Lancet
(1998) Treatment of mild hypertension: a five year controlled drug trial
Am J Med
(1980)