title: 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.
authors.affiliation: Faculty of Medicine, University of Toronto, Toronto, ON, Canada; School of Nursing, McMaster University, Hamilton, ON, Canada.
authors.forename: Leo
authors.initials: L
authors.lastname: Akioyamen
authors.affiliation: Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, ON, Canada; Programs for Assessment of Technology in Health (PATH) Research Institute, St. Joseph's Healthcare, Hamilton, ON, Canada.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Levine
authors.affiliation: School of Nursing, McMaster University, Hamilton, ON, Canada; Diabetes Care and Research Program, Hamilton Health Sciences, Hamilton, ON, Canada.
authors.forename: Diana
authors.initials: D
authors.lastname: Sherifali
authors.affiliation: Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, ON, Canada; Programs for Assessment of Technology in Health (PATH) Research Institute, St. Joseph's Healthcare, Hamilton, ON, Canada.
authors.forename: Daria
authors.initials: D
authors.lastname: O'Reilly
authors.affiliation: Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Claudia
authors.initials: C
authors.lastname: Frankfurter
authors.affiliation: Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, ON, Canada; Child Health Evaluative Sciences Program, The Hospital for Sick Children (SickKids), Toronto, ON, Canada.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Pullenayegum
authors.affiliation: Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, ON, Canada; Programs for Assessment of Technology in Health (PATH) Research Institute, St. Joseph's Healthcare, Hamilton, ON, Canada.
authors.forename: Ron
authors.initials: R
authors.lastname: Goeree
authors.affiliation: Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, ON, Canada; Programs for Assessment of Technology in Health (PATH) Research Institute, St. Joseph's Healthcare, Hamilton, ON, Canada. Electronic address: tsoib@mcmaster.ca.
authors.forename: Bernice
authors.initials: B
authors.lastname: Tsoi
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology; D000075222:Essential Hypertension; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D000069451:Long Term Adverse Effects / Q000145:classification / Q000401:mortality / Q000628:therapy; D060735:Pharmacovigilance
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents
keywords: Systematic review; angiotensin receptor blocker; heart failure; hypertension; meta-analysis; mortality; myocardial infarction; stroke