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Review
. 2012 Aug;33(16):2088-97.
doi: 10.1093/eurheartj/ehs075. Epub 2012 Apr 17.

Angiotensin-converting enzyme inhibitors reduce mortality in hypertension: a meta-analysis of randomized clinical trials of renin-angiotensin-aldosterone system inhibitors involving 158,998 patients

Laura C van Vark  1 , Michel Bertrand, K Martijn Akkerhuis, Jasper J Brugts, Kim Fox, Jean-Jacques Mourad, Eric Boersma
Affiliations
Review

Angiotensin-converting enzyme inhibitors reduce mortality in hypertension: a meta-analysis of randomized clinical trials of renin-angiotensin-aldosterone system inhibitors involving 158,998 patients

Laura C van Vark et al. Eur Heart J. 2012 Aug.

Abstract

Aims: Renin-angiotensin-aldosterone system (RAAS) inhibitors are well established for the reduction in cardiovascular morbidity, but their impact on all-cause mortality in hypertensive patients is uncertain. Our objective was to analyse the effects of RAAS inhibitors as a class of drugs, as well as of angiotensin-converting enzyme (ACE) inhibitors and AT1 receptor blockers (ARBs) separately, on all-cause mortality.

Methods and results: We performed a pooled analysis of 20 cardiovascular morbidity-mortality trials. In each trial at least two-thirds of the patients had to be diagnosed with hypertension, according to the trial-specific definition, and randomized to treatment with an RAAS inhibitor or control treatment. The cohort included 158 998 patients (71 401 RAAS inhibitor; 87 597 control). The incidence of all-cause death was 20.9 and 23.3 per 1000 patient-years in patients randomized to RAAS inhibition and controls, respectively. Overall, RAAS inhibition was associated with a 5% reduction in all-cause mortality (HR: 0.95, 95% CI: 0.91-1.00, P= 0.032), and a 7% reduction in cardiovascular mortality (HR: 0.93, 95% CI: 0.88-0.99, P= 0.018). The observed treatment effect resulted entirely from the class of ACE inhibitors, which were associated with a significant 10% reduction in all-cause mortality (HR: 0.90, 95% CI: 0.84-0.97, P= 0.004), whereas no mortality reduction could be demonstrated with ARB treatment (HR: 0.99, 95% CI: 0.94-1.04, P= 0.683). This difference in treatment effect between ACE inhibitors and ARBs on all-cause mortality was statistically significant (P-value for heterogeneity 0.036).

Conclusion: In patients with hypertension, treatment with an ACE inhibitor results in a significant further reduction in all-cause mortality. Because of the high prevalence of hypertension, the widespread use of ACE inhibitors may result in an important gain in lives saved.

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Figures

Figure 1
Figure 1
Flow diagram of trial search and selection process. RAAS, renin–angiotensin–aldosterone system; RCT, randomized clinical trials.
Figure 2
Figure 2
All-cause and cardiovascular mortality treatment effect of renin–angiotensin–aldosterone system blockade in all included trials. HR, hazard ratio; CI, confidence interval; RAAS, renin–angiotensin–aldosterone system. Overall P= 0.032 for all-cause mortality. Overall P= 0.018 for cardiovascular mortality.
Figure 3
Figure 3
The all-cause mortality treatment effect of ACE inhibitor and ARB trials. HR, hazard ratio; CI, confidence interval; ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker. P= 0.004 for the treatment effect of ACE inhibitor on all-cause mortality. P= 0.683 for the treatment effect of ARB on all-cause mortality.
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