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