ANGIOTENSIN-CONVERTING ENZYME INHIBITORS & ANGIOTENSIN RECEPTOR BLOCKERS ON RISK OF MORTALITY: A META-ANALYSIS OF RANDOMIZED-CONTROLLED TRIALS INVOLVING 317,984 PATIENTS

Abstract

Objective: To evaluate the effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) on all-cause & cardiovascular (CV) mortality in patients with or at high-risk of CV diseases Design and method: We performed a meta-analysis with data from randomized-controlled trials. Bibliographic databases were searched until 31 July 2019 for ACEIs & ARBs trials versus placebo or active therapy & supported with head-to-head trials in people with or at high-risk of CV diseases. Only trials with at least 100 participants and at least one year of follow-up were included. Studies were excluded if they were redacted or combined ACEIs with ARBs. Outcomes were all-cause mortality & CV mortality. Dichotomous outcomes data were analysed using risk ratio (RR) measure and its 95% CI with random-effects model. A random-effects meta-regression analysis was performed to explore role systolic blood pressure (SBP) reduction achieved. Results: 97 trials with 317,984 patient-years of follow-up were included. Patients were randomly assigned to ACEIs in 42 trials, ARBs in 45 trials compared with control (placebo or active) & 10 trials compared ACEIs and ARBs head-to-head. Compared with control, those assigned to ACEIs had a 5% lower all-cause (RR, 0.95; 95% 0.91–0.98; p = 0.003) & 9% lower CV (RR, 0.91; 95% CI 0.86–0.97; p = 0.002) mortality. Whereas, no all-cause (RR, 0.99; 0.96–1.02; p = 0.55) & CV (RR, 0.99; 95% CI 0.94–1.05; p = 0.73) mortality could be demonstrated with ARBs therapy. However, head-to-head trials exhibited no difference between ARBs & ACEIs on either all-cause (RR, 1.03; 95% CI 0.98–1.08; p = 0.20) or CV (RR, 1.04; 95% CI 0.98–1.10; p = 0.16) mortality. The meta-regression analysis suggested that the effect of ACEIs on all-cause mortality and CV death was due to reduction in systolic blood pressure (SBP); p-value is 0.01 & 0.02; respectively. This did not appear to be the case for ARBs. Conclusions: ACEIs appear effective in reducing mortality; the evidence for ARBs appears less secure. The effect of ACEIs are associated with and may be due to a reduction in SBP.