Assessing the risk of angiotensin receptor blockers on major cardiovascular events: a systematic review and meta-analysis of randomized controlled trials

Background Angiotensin receptor blockers (ARBs) are commonly used as a treatment for many cardiovascular diseases, but their safety has been called into question. The VALUE trial found an increased risk of myocardial infarction in participants receiving ARBs compared to other antihypertensive. The aim of the meta-analysis was to synthetize the available evidence of randomised controlled trials (RCTs) and elucidate if ARBs increase the risk of cardiovascular events. Methods A comprehensive search was conducted to identify RCTs that assessed the safety of ARBs. Titles and abstracts of all papers were independently screened by two authors. Data extraction and quality assessment were also performed independently. The relative risk (RR) of all-cause mortality, myocardial infarction, and stroke were pooled using the IVhet model. Multiple sensitivity analyses were conducted to assess the effect of ARBs by restricting the analysis to different participants' characteristics. Results Forty-five RCTs comprising of 170,794 participants were included in the analysis. The pooled estimates revealed that ARBs do not increase the risk of all-cause mortality (RR 1.00; 95%CI 0.97-1.04), myocardial infarction (RR 1.01; 95%CI 0.96-1.06), and stroke (RR 0.92; 95%CI 0.83-1.01). The sensitivity analysis did not yield a particular group of patients at increased risk of cardiovascular events with ARBs. Risk of all-cause mortality and stroke decreased with ARB when the proportion of smokers in a population was < 25% (RR 0.91; 95%CI 0.84-0.98) and in females (RR 0.76; 95%CI 0.68-0.84), respectively. Conclusions ARBs do not increase the risk of major cardiovascular events and are safe for use in patients.