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
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Why the study?
RAAS inhibitors reduce cardiovascular morbidity, but their impact on all-cause mortality in hypertensive patients was uncertain.
Do RAAS inhibitors (ACE inhibitors and ARBs) reduce all-cause mortality in patients with hypertension?
Structured PICO
Do RAAS inhibitors (ACE inhibitors and ARBs) reduce all-cause mortality in patients with hypertension?
P
Population
158,998 patients from 20 cardiovascular morbidity-mortality trials where at least two-thirds of patients were diagnosed with hypertension
I
Intervention
Renin-angiotensin-aldosterone system (RAAS) inhibitors as a class, and specifically ACE inhibitors and ARBs
C
Comparator
Control treatment
O
Outcome
All-cause mortalityhard clinical
In hypertensive patients, ACE inhibitors, but not ARBs, significantly reduce all-cause mortality, suggesting a class-specific mortality benefit.
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The guideline recommended goal of antihypertensive treatment is mortality reduction, however this is the first study that scientifically evaluates the value of RAAS inhibitors on mortality in their main indication of hypertension.”
“There has been debate for many years over the safety and efficacy of ACE inhibitors compared to ARBs, with many of them using an 'ACE inhibitor-first' approach, with ARBs regarded as less effective. We believe that our study ends the debate and gives physicians the option to prescribe either drug for their patients.”
“Many placebo trials have shown significant benefits with ACE inhibitors, while no such benefits were shown for angiotensin receptor blockers. Most of the time, positive trials can tend to have a long-lasting, lingering effect. Because of this, most physicians and many guidelines still consider ACE inhibitors to be superior, despite the fact that head-to-head trials comparing ACE inhibitors and angiotensin receptor blockers have shown similar outcomes.”
Implication
Supports ACE inhibitor preference over ARBs in hypertension; confirms mortality benefit while challenging class equivalence.
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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Cite This Study
Vark et al. (2012) studied this question.