European Heart Journal Advance Access published online on January 23, 2009
European Heart Journal, doi:10.1093/eurheartj/ehn575
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Blood pressure reduction and renin–angiotensin system inhibition for prevention of congestive heart failure: a meta-analysis
1 Ospedale S. Maria della Misericordia, Cardiologia, Perugia, Italy
2 Dipartimento di Medicina Interna, Università di Perugia, Perugia, Italy
3 Division of Hypertension and Cardiovascular Research, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium
4 Department of Epidemiology, University of Maastricht, Maastricht, The Netherlands
Received 18 May 2008; revised 15 November 2008; accepted 27 November 2008.
* Corresponding author: Unità di Ricerca Clinica ‘Cardiologia Preventiva’, Ospedale ‘S. Maria della Misericordia’, Piazzale G. Menghini, 06132 Perugia, Italy. Tel: +39 075 5782213, Fax: +39 075 5782214, Email: verdec{at}tin.it
Aims: It is unclear whether prevention of congestive heart failure (CHF) by drugs that inhibit the renin–angiotensin system (RAS) occurs over and beyond the reduction in blood pressure (BP) achieved by these drugs.
Methods and results: We conducted a meta-analysis of trials comparing angiotensin-converting enzyme inhibitors (ACEIs), angiotensin-receptor blockers (ARBs), or calcium-channel blockers (CCBs), with diuretics, β-blockers, or placebo in hypertensive or high-risk subjects without CHF at entry. Both fixed- and random-effect models were used. In trials vs. placebo, the risk of CHF was reduced by 21% with ACEIs (P = 0.007), whereas the effect of ARBs and CCBs was not significant (random-effect models). Thus, CCBs did not increase the risk of CHF. In trials vs. diuretics/β-blockers, no differences were found between ACEIs and comparators [odds ratio (OR) 1.02; 95% confidence interval (CI) 0.84–1.24], whereas CCBs were associated with an 18% higher risk of CHF (OR 1.18; 95% CI 1.00–1.39; P = 0.048). Therefore, ACEIs were not superior to diuretics/β-blockers for the prevention of CHF. Because heterogeneity between trials was significant, we investigated potential sources of heterogeneity by meta-regression. The risk of CHF decreased by 24% (P < 0.001) for each 5 mmHg reduction in systolic BP. The risk of CHF was 19% less with ACEIs/ARBs than CCBs (P < 0.001) and 16% less in studies without multiple risk factors required for entry (P = 0.009).
Conclusion: BP reduction is beneficial for the prevention of CHF. Over and beyond BP reduction, the protective effect of ACEIs and ARBs is greater than that of CCBs.
Key Words: Hypertension • Therapy • Congestive heart failure • Myocardial infarction • Sudden cardiac death • Unstable angina • Stroke • Prognosis • Prevention • Meta-analysis • Meta-regression
This paper was guest edited by Prof. Lars Kober, The Heart Centre, University Hospital of Copenhagen, Copenhagen, Denmark
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