Elsevier

The Lancet

Volume 362, Issue 9395, 8 November 2003, Pages 1527-1535
The Lancet

Articles
Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials

https://doi.org/10.1016/S0140-6736(03)14739-3Get rights and content

Summary

Background

The benefits of reducing blood pressure on the risks of major cardiovascular disease are well established, but uncertainty remains about the comparative effects of different blood-pressure-lowering regimens. We aimed to estimate effects of strategies based on different drug classes (angiotensin-converting-enzyme [ACE] inhibitors, calcium antagonists, angiotensin-receptor blockers [ARBs], and diuretics or β blockers) or those targeting different blood pressure goals, on the risks of major cardiovascular events and death.

Methods

We did seven sets of prospectively-designed overviews with data from 29 randomised trials (n=162 341). The trial eligibility criteria, primary outcomes, and main hypotheses were specified before the result of any contributing trial was known.

Findings

In placebo-controlled trials the relative risks of total major cardiovascular events were reduced by regimens based on ACE inhibitors (22%; 95% CI 17–27) or calcium antagonists (18%; 5–29). Greater risk reductions were produced by regimens that targeted lower blood pressure goals (15%; 5–24). ARB-based regimens reduced the risks of total major cardiovascular events (10%; 4–17) compared with control regimens. There were no significant differences in total major cardiovascular events between regimens based on ACE inhibitors, calcium antagonists, or diuretics or β blockers, although ACE-inhibitor-based regimens reduced blood pressure less. There was evidence of some differences between active regimens in their effects on cause-specific outcomes. For every outcome other than heart failure, the difference between randomised groups in achieved blood pressure reduction was directly related to the observed difference in risk.

Interpretation

Treatment with any commonly-used regimen reduces the risk of total major cardiovascular events, and larger reductions in blood pressure produce larger reductions in risk.

Introduction

Cardiovascular diseases are the leading cause of death worldwide;1 about two-thirds of the cerebrovascular disease burden and half the ischaemic heart disease burden are attributable to non-optimum blood pressure.2 The beneficial effects of blood-pressure-lowering treatments on the risks of major cardiovascular events are well established,3, 4, 5, 6, 7, 8 but little is known about the comparative effects of regimens based on different drug classes or regimens targeting different blood pressure goals.4, 9, 10 Reliable information about the size of benefits achieved with different blood-pressure-lowering regimens is of great importance—if one regimen proved even slightly better than another, then preferential use of the more effective regimen might prevent tens of thousands of major cardiovascular events every year.

The uncertainty about the comparative effects of different regimens in part reflects the limited statistical power of most individual studies to identify plausible differences in the size of treatment effects, and differences between studies in selection of patients, choice of outcome definitions, and achieved blood pressure reductions. The Blood Pressure Lowering Treatment Trialists' Collaboration was established to undertake a series of prospectively-designed systematic overviews to investigate the effects of different blood-pressure-lowering regimens on mortality and major cardiovascular events.11 Results of the first round of analyses were reported in 2000.4 The first meta-analyses showed benefits of blood-pressure-lowering regimens based on angiotensin-converting-enzyme (ACE) inhibitors and those based on calcium antagonists, compared with placebo, but did not provide definitive evidence about comparative effects of regimens based on different drug classes and those targeting different blood pressure goals. In these analyses we aimed to resolve some of these issues.

Section snippets

Methods

The methods used by the Blood Pressure Lowering Treatment Trialists' Collaboration have been reported previously,4, 11 and only the main components are summarised here. Trial eligibility criteria, blood pressure lowering regimens to be compared, and primary outcomes were all prespecified.11

Trials and patients

Table 1 shows characteristics of the 29 trials12, 13, 14, 15, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 44 (162 341 participants) that were included. Nine trials (25 711 participants, 3548 major vascular events) provided data from comparisons of an ACE-inhibitor-based or a calcium-antagonist-based regimen versus placebo, and five (21982 participants, 1191 major vascular events) provided data from comparisons of regimens targeting

Heart failure

For heart failure that caused death or admission to hospital, there was a beneficial effect from ACE inhibitor-based regimens compared with placebo (18% [2–31]; figure 1). There was no clear effect of calcium-antagonist-based regimens (21% [−42 to 7]) or regimens targeting lower blood pressure goals (16% [−18 to 41]), although the CIs were wide for both. Compared with control regimens, ARB-based treatment reduced the risk of heart failure (16% [3–28]; figure 2). Effects of regimens based on ACE

Discussion

Our results show that treatment with any commonly-used regimen reduces the risk of total major cardiovascular events, and that larger reductions in blood pressure produce larger reductions in risk. These results confirm earlier analyses4 showing benefits of ACE-inhibitor-based regimens across a wide range of hypertensive and non-hypertensive patients at high risk of cardiovascular disease, and of calcium-antagonist-based regimens in hypertensive patients.

The results of this meta-analysis also

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