Professor Juan Tamargo, Madrid, Spain

A meta-analysis of randomised clinical trials of renin-angiotensin-aldosterone system inhibitors involving 158,998 patients has shown that these drugs reduce mortality in hypertension.

Renin-angiotensin-aldosterone system (RAAS) inhibitors are well established in the reduction in cardiovascular morbidity, but their impact on all-cause mortality in hypertensive patients is uncertain. In order to address this question, Van Bark et al (2012) [1] analyzed the effects of angiotensin-converting enzyme (ACE) inhibitors and AT1 receptor blockers (ARBs) separately, on all-cause mortality in 20 cardiovascular morbidity-mortality trials performed between 2000 and 2011.

In each trial at least two-thirds of the patients had to be diagnosed with hypertension and randomized to treatment with an RAAS inhibitor or control treatment. The cohort included 158,998 patients (71,401 received RAAS inhibitors and 87,597 control treatment). However, three trials (INVESTACCOMPLISH, and ONTARGET) were excluded from the analysis because RAAS inhibitors were used simultaneously in both trial arms.

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 effects were attributed to the use 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 on all-cause mortality was statistically significant (P-value for heterogeneity = 0.036).


1. van Vark LCBertrand MAkkerhuis KMBrugts JJFox KMourad JJBoersma E. 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. Eur Heart J. 2012 Apr 17. [Epub ahead of print]
Cardio Debate Expert Comments

This meta-analysis shows, in contrast to other previous meta-analysis showing a therapeutic equivalence between ACE inhibitors and ARBs regarding clinical outcomes such as MI and stroke, that in hypertensive patients treatment with ACE inhibitors results in a significant reduction in all-cause mortality. Thus, these important findings provide the rationale to treat hypertensive patients with ACE inhibitors.