Sex Differences in the Efficacy of Angiotensin Receptor Blockers in Blood Pressure Lowering and Cardiac Remodeling: A Systematic Review and Meta-Analysis

Abstract

Background: Hypertension is the leading risk factor for cardiovascular disease (CVD) in females. While treatment of high BP is essential in the global prevention strategies of CVD it is assumed that effectiveness of pharmacological treatment may be different across sexes. Objective: The aim of this systematic review and meta-analysis was to evaluate sex-stratified effects for angiotensin receptor blockers (ARBs) on blood pressure (BP), heart rate and cardiac function in female compared to male hypertensive individuals. Design and methods: We performed a series of systematic reviews and meta-analysis after we systematically searched PubMed and EMBASE for studies evaluating the effects of the five major groups of antihypertensive medication from 1945 to May 2020. We included randomized control trials and observational studies in humans (≥18 years) investigating Beta-blockers (BB), angiotensin converting enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARB), calcium channel blockers (CCB), and diuretics. In this study we analysed data on ARB’s. Studies had to present both baseline and follow-up measurements of at least one of the outcome variables of interest and present their data in a sex-stratified manner. Data on BP, heart rate and cardiac function were retrieved from studies. Mean differences between baseline and follow-up were calculated using a random-effects model. Intervention effect was assessed for the acute (0-14 days), subacute (15-30 days) and chronic (>31 days) phase. Results: The search strategy resulted in 73,867 hits. After first screening based on title and abstract, 15,130 articles were suitable for full text screening. After excluding all studies that matched our exclusion criteria, 205 studies were eligible for analysis for the five antihypertensive drugs. Studies investigating ARB´s (n=17) were used in this review. ARB decreased BP significantly but comparably in both female and male; systolic BP -18.2 mmHg (95% CI, -24.8; -11.5) vs -20.1 mmHg (95% CI, -26.7; -13.6) and diastolic BP -11.6 mmHg (95% CI, -14.7; -8.4) vs -12.3 mmHg (95% CI, -16.4; -8.1). Left ventricular ejection fraction (LVEF) did not change significantly in either group. Left ventricle (LV) mass was only reported in males and did not change statistically significant -11.8 g (95% CI, -25.6; 1.9). Conclusion: ARB’s decreased BP in both female and male hypertensive patients substantially but comparably.