Cardiovascular and cerebrovascular outcomes of long-term angiotensin receptor blockade: meta-analyses of trials in essential hypertension

Abstract

Angiotensin receptor blockers (ARBs) are widely used in managing essential hypertension, with considerable evidence available on their short-term efficacy in lowering blood pressure (BP). However, there currently exists limited "pooled" data examining the long-term efficacy of ARB treatment in controlling BP or mitigating cardiovascular and cerebrovascular events. The purpose of this study was to conduct a systematic review and meta-analysis assessing the long-term effects of ARBs as a class on BP control, myocardial infarction, hospitalization for heart failure, cerebrovascular events (ie, stroke), cardiovascular mortality, and all-cause mortality. MEDLINE, EMBASE, PubMed, and the Cochrane Library databases were searched from inception to March 2015. Two evaluators independently reviewed studies for eligibility. Randomized controlled hypertension trials were included if they reported on ARB efficacy in either BP control (relative to placebo for periods ≥ 6 months) or cardiovascular/cerebrovascular outcomes (relative to non-ARB antihypertensive therapies for periods ≥ 24 months). Studies were pooled with a random-effects model using weighted mean differences (WMDs) and relative risks for continuous and dichotomous outcomes, respectively. A total of 11 articles were included in the narrative synthesis, representing seven unique trials (16,864 participants). Six ARB agents were studied: candesartan, eprosartan, irbesartan, olmesartan, losartan (each represented by one trial arm), and telmisartan (represented by two arms). ARB therapy significantly reduced mean systolic BP (WMD: -4.86; 95% CI: -6.19, -3.53 mm Hg) and diastolic BP (WMD: -2.75; 95% CI: -3.65, -1.86 mm Hg] compared to placebo. The risk of stroke was reduced by 21% in the ARB group compared with alternative antihypertensives (risk ratio: 0.79; 95% CI: 0.66, 0.96). ARBs did not, however, produce statistically significant reductions in the risk of myocardial infarction, heart failure hospitalization, or mortality. Our findings suggest that ARBs, as a class, are more effective than placebo therapy in long-term BP lowering in patients with essential hypertension. Long-term ARB treatment may also confer enhanced protection against stroke but not other cardiovascular outcomes relative to placebo.

Keywords: Systematic review; angiotensin receptor blocker; heart failure; hypertension; meta-analysis; mortality; myocardial infarction; stroke.