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Effects of blood pressure lowering on outcome incidence in hypertension: 4. Effects of various classes of antihypertensive drugs – Overview and meta-analyses

Thomopoulos, Costasa; Parati, Gianfrancob,c; Zanchetti, Albertod,e

doi: 10.1097/HJH.0000000000000447

Background and objectives: In 68 randomized controlled trials (RCTs), blood pressure (BP) lowering was obtained by using drugs of different classes. We have investigated whether BP lowering by any of the major drug classes is effective in reducing the cardiovascular outcomes.

Methods: A total of 55 RCTs (195 267 individuals) were suitable for drug-class meta-analyses. Risk ratios and their 95% confidence intervals of seven fatal and nonfatal outcomes were estimated by a random-effects model.

Results: Twelve RCTs (48 898 patients) compared a diuretic with no treatment. SBP/DBP differences of about −12/–5 mmHg were accompanied by significant reductions of all outcomes, including mortality. The same results were obtained by limiting analyses to eight RCTs using low-dose diuretics. Separate analyses for thiazides, chlorthalidone and indapamide (all low dose) showed each subclass was associated with significant reduction of some major outcome. Five RCTs (18 724 patients; SBP/DBP difference –10.5/–7 mmHg) showed beta-blockers significantly reduced stroke, heart failure and major cardiovascular events. In RCTs comparing calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) with placebo smaller SBP/DBP differences were achieved, mostly because in the majority of these later RCTs the antihypertensive drug and placebo were added on a background treatment with other antihypertensive agents. Nonetheless, significant reductions of stroke, major cardiovascular events, cardiovascular and all-cause death were obtained with calcium antagonists (10 RCTs, 30 359 patients); stroke, coronary heart disease, heart failure and major cardiovascular events by ACE inhibitors (12 RCTs, 35 707 patients); and stroke, heart failure and major cardiovascular events by ARBs (13 RCTs, 65 256 patients).

Conclusion: BP lowering by all classes of antihypertensive drugs is accompanied by significant reductions of stroke and major cardiovascular events. This supports the concept that reduction of these events is because of BP lowering per se rather than specific drug properties. However, evidence of risk reduction of other events and particularly mortality was obtained so far with some drug classes only. As a result of marked differences in the trial design, total cardiovascular risk, SBP/DBP differences and statistical power, comparisons of meta-analyses of different drug-specific placebo-controlled RCTs appear unwarranted.

aDepartment of Cardiology, Helena Venizelou Hospital, Athens, Greece

bDepartment of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Istituto Auxologico Italiano IRCCS

cDepartment of Health Sciences, University of Milan Bicocca

dScientific Direction, Istituto Auxologico Italiano IRCCS

eCentro Interuniversitario di Fisiologia Clinica e Ipertensione, University of Milan, Milan, Italy

Correspondence to Alberto Zanchetti, Professor, Direzione Scientifica, Istituto Auxologico Italiano, Via L. Ariosto, 13, I-20145 Milan, Italy. Tel: +39 2 619112237; fax: +39 2 619112901; e-mail:

Abbreviations: ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; BP, blood pressure; BPLTTC, Blood Pressure Lowering Treatment Trialists’ Collaboration; CHD, coronary heart disease; CI, confidence interval; n, number; NNT, number needed to treat; RCT, randomized controlled trial; RR, risk ratio

Received 16 September, 2014

Revised 8 October, 2014

Accepted 8 October, 2014

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