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

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Sophie AJS Laven, MD Daniek AM Meijs, MD Zenab Mohseni-Alsalhi, MSc Esmée W. P. Vaes, MD Nick Wilmes, MD Eveline M van Luik, MD Maud AM Vesseur, MD Sander de Haas, MSc, MD Chahinda Ghossein-Doha, MD, PhD Marc EA Spaanderman, MD, PhD


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.

Keywords: hypertension, angiotensin receptor blockers, sex differences

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How to Cite
LAVEN, Sophie AJS et al. Sex Differences in the Efficacy of Angiotensin Receptor Blockers in Blood Pressure Lowering and Cardiac Remodeling: A Systematic Review and Meta-Analysis. Medical Research Archives, [S.l.], v. 11, n. 10, oct. 2023. ISSN 2375-1924. Available at: <>. Date accessed: 29 nov. 2023. doi:
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1. Shin MS, Kang DR, Kim C, Cho EJ, Sung KC, Kang SM, et al. Fimasartan for independent reduction of BP variability in mild-to-moderate hypertension. Drug Des Devel Ther. 2016;10:1573-80.
2. Axelsson A, Iversen K, Vejlstrup N, Ho C, Norsk J, Langhoff L, et al. Efficacy and safety of the angiotensin II receptor blocker losartan for hypertrophic cardiomyopathy: the INHERIT randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2015;3(2):123-31.
3. Spoelstra-de Man AM, van Ittersum FJ, Schram MT, Kamp O, van Dijk RA, Ijzerman RG, et al. Aggressive antihypertensive strategies based on hydrochlorothiazide, candesartan or lisinopril decrease left ventricular mass and improve arterial compliance in patients with type II diabetes mellitus and hypertension. J Hum Hypertens. 2006;20(8):599-611.
4. Cottone S, Vadala A, Vella MC, Nardi E, Mule G, Contorno A, et al. Changes of plasma endothelin and growth factor levels, and of left ventricular mass, after chronic AT1-receptor blockade in human hypertension. Am J Hypertens. 1998;11(5):548-53.
5. Malmqvist K, Kahan T, Edner M, Held C, Hagg A, Lind L, et al. Regression of left ventricular hypertrophy in human hypertension with irbesartan. J Hypertens. 2001;19(6):1167-76.
6. Baysal SS, Pirat B, Okyay K, Bal UA, Ulucam MZ, Oztuna D, et al. Treatment-associated change in apelin concentration in patients with hypertension and its relationship with left ventricular diastolic function. Anatol J Cardiol. 2017;17(2):125-31.
7. Oh MS, Yu KH, Hong KS, Kang DW, Park JM, Bae HJ, et al. Modest BP reduction with valsartan in acute ischemic stroke: a prospective, randomized, open-label, blinded-end-point trial. Int J Stroke. 2015;10(5):745-51.
8. Lee SE, Kim YJ, Lee HY, Yang HM, Park CG, Kim JJ, et al. Efficacy and tolerability of fimasartan, a new angiotensin receptor blocker, compared with losartan (50/100 mg): a 12-week, phase III, multicenter, prospective, randomized, double-blind, parallel-group, dose escalation clinical trial with an optional 12-week extension phase in adult Korean patients with mild-to-moderate hypertension. Clin Ther. 2012;34(3):552-68, 68 e1-9.
9. Voors AA, van de Wal RM, Hartog JW, Vijn RG, Hummel YM, Plokker TW, et al. Effects of eprosartan on diastolic function and neurohormones in patients with hypertension and diastolic dysfunction. Cardiovasc Drugs Ther. 2010;24(1):33-40.
10. Kasanuki H, Hagiwara N, Hosoda S, Sumiyoshi T, Honda T, Haze K, et al. Angiotensin II receptor blocker-based vs. non-angiotensin II receptor blocker-based therapy in patients with angiographically documented coronary artery disease and hypertension: the Heart Institute of Japan Candesartan Randomized Trial for Evaluation in Coronary Artery Disease (HIJ-CREATE). Eur Heart J. 2009;30(10):1203-12.
11. Zakynthinos E, Pierrutsakos C, Daniil Z, Papadogiannis D. Losartan controlled BP and reduced left ventricular hypertrophy but did not alter arrhythmias in hypertensive male with preserved systolic function. Angiology. 2005;56(4):439-49.
12. Sanem Nalbantgil HY, Cemil Gurun, Filiz Özerkan, Istemi Nalbantgil, Remzi Önder. . Effects of valsartan and enalapril on regression of left ventricular hypertrophy in patients with mild to moderate hypertension: A randomized, double-blind study. . Current Therapeutic Research. 2000;61(6):331-8.
13. Vescovo G, Dalla Libera L, Serafini F, Leprotti C, Facchin L, Volterrani M, et al. Improved exercise tolerance after losartan and enalapril in heart failure: correlation with changes in skeletal muscle myosin heavy chain composition. Circulation. 1998;98(17):1742-9.
14. Os I, Franco V, Kjeldsen SE, Manhem K, Devereux RB, Gerdts E, et al. Effects of losartan in female with hypertension and left ventricular hypertrophy: results from the Losartan Intervention for Endpoint Reduction in Hypertension Study. Hypertension. 2008;51(4):1103-8.
15. Cuocolo A, Storto G, Izzo R, Iovino GL, Damiano M, Bertocchi F, et al. Effects of valsartan on left ventricular diastolic function in patients with mild or moderate essential hypertension: comparison with enalapril. J Hypertens. 1999;17(12 Pt 1):1759-66.
16. Yamazaki T, Suzuki J, Shimamoto R, Tsuji T, Ohmoto-Sekine Y, Ohtomo K, et al. A new therapeutic strategy for hypertrophic nonobstructive cardiomyopathy in humans. A randomized and prospective study with an Angiotensin II receptor blocker. Int Heart J. 2007;48(6):715-24.
17. Mehlum MH, Liestol K, Kjeldsen SE, Wyller TB, Julius S, Rothwell PM, et al. Blood Pressure-Lowering Profiles and Clinical Effects of Angiotensin Receptor Blockers Versus Calcium Channel Blockers. Hypertension. 2020;75(6):1584-92.