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.
Section snippets
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
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