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.

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.

Objective: To evaluate the effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) on risk of myocardial infarction (MI), angina & heart failure (HF) in patients with or at high-risk of cardiovascular disease (CVD). Design and method: A meta-analysis of randomized-controlled trials was performed. Bibliographic databases were searched until 31 July 2019 to identify all trials of ACEIs & ARBs versus control (placebo or active) & supported with head-to-head trials. Trials with at least 100 participants & at least one year's follow-up were eligible. Studies were excluded if they were redacted or combined ACEIs with ARBs. Outcomes were MI, angina pectoris & HF. Dichotomous 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: We identified 32 trials of ACEIs, 38 of ARBs compared with control & 8 direct comparison trials. Altogether, trials enrolled 299,871 patient-years of follow-up. Compared with control, ACEIs had a 16% lower MI risk (RR, 0.84; 95% CI, 0.79–0.90; p < 0.00001) & 17% lower HF (RR, 0.83; 95% CI, 0.76–0.92; p = 0.0003); while no such benefit was seen for angina (RR;1.02; 95% CI, 0.94–1.11; p = 0.63). ARBs was reduced risk of HF by 14% (RR, 0.86; 95% CI 0.81–0.91; p < 0.00001). While, no benefit was appeared with MI risk (RR,0.97; 95% CI 0.89–1.06; p = 0.55) & angina (RR, 0.99; 95% CI 0.88–1.11; p = 0.87). Trials comparing ARBs with ACEIs revealed no difference in outcomes. The meta-regression suggested that independently of BP reduction, ACEIs had a 11% lower MI (RR,0.89; 95% CI 0.81–0.98; p = 0.02) & ARBs provide a 15% reduction in HF (RR, 0.85; 95% CI 0.77–0.93; p = 0.001). Whereas, prevention of HF by ACEIs was explained mainly by SBP reduction achieved (p = 0.01). Conclusions: In patients with or at high-risk of CVD, ARBs and ACEIs reduced risk of HF. However, they did not appear to be case for angina. Moreover, ACEIs result in a further reduction of MI whereas ARBs had no such benefit. However, evidence from direct comparison trials suggests similar effects on all outcomes.