ANGIOTENSIN-CONVERTING ENZYME INHIBITORS AND ANGIOTENSIN RECEPTOR BLOCKERS IN STROKE PREVENTION: A SYSTEMATIC REVIEW AND META-ANALYSIS INVOLVING 297,451 PATIENTS

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Abstract Objective : To assess the impact of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) on risk of stroke in patients with or at high-risk of cardiovascular diseases (CVD) Design and method: A meta-analysis of randomized-controlled trials was performed. Bibliographic databases were searched until 31 July 2019 for ACEIs & ARBs trials versus placebo or active therapy & supported with head-to-head trials in participants with or at high-risk of CVD. Only trials with at least 100 participants & at least one year's follow-up were included. Trials were excluded if they were redacted or combined ACEIs with ARBs. Outcome was fatal & non-fatal stroke: including ischaemic and haemorrhagic stroke excluded transient ischaemic attack (TIA). Dichotomous outcome data was analysed using risk ratio (RR) measure and its 95% confidence interval (CI) with random-effects model. A random-effects meta-regression analysis was performed to explore role systolic blood pressure (SBP) reduction achieved. Results: This study included 72 trials with 297,451 patient-years of follow-up. Compared with placebo, both ACEIs and ARBs reduced the risk of stroke by 14% & 9%; respectively (ACEIs: RR, 0.86; 95% CI, 0.76–0.98; p = 0.02 & ARBs: RR, 0.91; 95% CI, 0.86–0.97; p = 0.003). No difference was observed when ACEIs & ARBs were compared with active (ACEIs: RR, 1.14; 95% CI, 1.04–1.26; p = 0.006 & ARBs: RR, 0.94; 95% CI 0.79–1.12; p = 0.50). Pooled data from trials comparing ARBs to ACEIs showed no difference in stroke event rates (RR, 0.96; 95% 0.87–1.06; p = 0.42). A meta-regression analysis revealed that the relative risk reduction of stroke by ACEIs (p = 0.03) and ARBs (p = 0.01) therapy was proportional to the magnitude of SBP reduction achieved. Conclusions: In patients with or at high-risk of CVD, evidence from placebo-controlled trials & head-to-head trials demonstrated that ARBs to be as effective as ACEIs on preventing of stroke. Cerebro-protective effect of ARBs & ACEIs therapies are strongly associated with BP reduction.