Exploring Sex Differences of Beta-Blockers in the Treatment of Hypertension: A Systematic Review and Meta-Analysis

Abstract

Aims: In the prevention of cardiovascular morbidity and mortality, early recognition and adequate treatment of hypertension are of leading importance. However, the efficacy of antihypertensives may be depending on sex disparities. Our objective was to evaluate and quantify the sex-diverse effects of beta-blockers (BB) on hypertension and cardiac function. We focussed on comparing hypertensive female versus male individuals.

Methods and results: A systematic search was performed for studies on BBs from inception to May 2020. A total of 66 studies were included that contained baseline and follow up measurements on blood pressure (BP), heart rate (HR), and cardiac function. Data also had to be stratified for sex. Mean differences were calculated using a random-effects model. In females as compared to males, BB treatment decreased systolic BP 11.1 mmHg (95% CI, -14.5; -7.8) vs. 11.1 mmHg (95% CI, -14.0; -8.2), diastolic BP 8.0 mmHg (95% CI, -10.6; -5.3) vs. 8.0 mmHg (95% CI, -10.1; -6.0), and HR 10.8 beats per minute (bpm) (95% CI, -17.4; -4.2) vs. 9.8 bpm (95% CI, -11.1; -8.4)), respectively, in both sexes' absolute and relative changes comparably. Left ventricular ejection fraction increased only in males (3.7% (95% CI, 0.6; 6.9)). Changes in left ventricular mass and cardiac output (CO) were only reported in males and changed -20.6 g (95% CI, -56.3; 15.1) and -0.1 L (95% CI, -0.5; 0.2), respectively.

Conclusions: BBs comparably lowered BP and HR in both sexes. The lack of change in CO in males suggests that the reduction in BP is primarily due to a decrease in vascular resistance. Furthermore, females were underrepresented compared to males. We recommend that future research should include more females and sex-stratified data when researching the treatment effects of antihypertensives.

Keywords: beta-blockers; hypertension; meta-analysis; sex differences; systematic review.

Figure 1

Flowchart of the systematic selection.

Figure 2

Forest plot of systolic blood pressure (SBP) change in mmHg after beta-blocker use compared to baseline for females and males [24,26,27,28,29,32,34,35,38,41,42,44,45,48,50,54,55,56,57,61,62,63,64,72,73,78,79,82,83,84,86]. MD = mean difference.

Figure 3

Meta-regression curve of systolic blood pressure (SBP) by beta-blocker treatment duration (days). Every circle represents one article, and the size represents the number of participants included in the study, shown as a small or larger circle.

Figure 4

Forest plot of diastolic blood pressure (DBP) change in mmHg after beta-blocker use compared to baseline for females and males [24,26,27,28,32,35,38,42,44,45,46,48,49,50,54,55,56,57,62,63,64,72,73,78,79,82,83,84]. MD = mean difference.

Figure 5

Meta-regression curve of diastolic blood pressure (DBP) by BB treatment duration (days). Every circle represents one article, and the size represents the number of participants included in the study, shown as a small or larger circle.

Figure 6

Meta-regression curve of mean arterial pressure (MAP) change in mmHg by BB treatment duration (days). Every circle represents one article, and the size represents the number of participants included in the study, shown as a small or larger circle.

Figure 7

Forest plot of cardiac output (CO) change in L/min after beta-blocker use compared to baseline for males [27,28,66,76,80]. MD = mean difference.

Figure 8

Forest plot of left ventricular ejection fraction (LVEF) change in % after beta-blocker use compared to baseline for females and males [25,27,29,31,32,33,34,40,41,42,45,48,54,63,65,66,67,68,69,72,73,77,84]. MD = mean difference.