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Effects of blood pressure-lowering treatment. 6. Prevention of heart failure and new-onset heart failure – meta-analyses of randomized trials

Thomopoulos, Costas; Parati, Gianfranco; Zanchetti, Alberto

doi: 10.1097/HJH.0000000000000848

Background and objectives: Relative effectiveness of blood pressure (BP)-lowering treatment on various outcomes was evaluated by meta-analyses restricted to randomized controlled trials (RCTs) measuring all major outcomes, and the question whether BP lowering and each class of antihypertensive agents prevent new-onset heart failure by meta-analyses limited to RCTs excluding baseline heart failure from randomization.

Methods: Source of these meta-analyses are our databases of BP-lowering RCTs vs placebo or less-active treatment, and head-to-head comparisons of different antihypertensive classes. Risk ratios (RRs) and 95% confidence intervals of seven outcomes were calculated by a random-effects model. The relationships of outcome reductions to BP differences were investigated by meta-regressions.

Results: First, 35 BP-lowering RCTs measured all outcomes, and heart failure [RR 0.63 (0.52–0.75)] and stroke [RR 0.58 (0.49–0.68)] were the outcomes most effectively prevented. Second, heart failure and stroke reductions were significantly related to SBP, DBP and pulse pressure reductions. Third, in 18 BP-lowering RCTs excluding baseline heart failure from recruitment, heart failure reduction (‘new-onset’ heart failure) [RR 0.58 (0.44–0.75)] was very similar to that in the entire set of RCTs. Fourth, in meta-analyses of head-to-head comparisons of different antihypertensive classes, calcium antagonists were inferior in preventing ‘new-onset’ heart failure [RR 1.16 (1.01–1.33)]. However, this inferiority disappeared when meta-analysis was limited to RCTs allowing concomitant use of diuretics, β-blockers or renin–angiotensin system blockers also in the calcium antagonist group [RR 0.96 (0.81–1.12)].

Conclusion: BP-lowering treatment effectively prevents ’new onset’ heart failure. It is suggested that BP lowering by calcium antagonists is effective as BP lowering by other drugs in preventing ‘new-onset’ heart failure, unless the trial design creates an unbalance against calcium antagonists.

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, Milan, Italy

dScientific Direction, Istituto Auxologico Italiano IRCCS

eCentro Interuniversitario di Fisiologia Clinica e Ipertensione, Università degli Studi di Milano, Milan, Italy

Correspondence to Professor Alberto Zanchetti, Direzione Scientifica, Istituto Auxologico Italiano, Via L. Ariosto, 13, I-20145 Milano, Italy. Tel: +39 02 619112237; fax: +39 02 619112901; e-mail:

Abbreviations: ACE, angiotensin converting enzyme; BP, blood pressure; CHD, coronary heart disease; CI, confidence interval; PP, pulse pressure; RCT, randomized controlled trial; RR, risk ratio (explanation of trial acronyms can be found in the referenced publications.)

Received 29 September, 2015

Revised 1 December, 2015

Accepted 10 December, 2015

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