Background: The leading global risk factor for cardiovascular-disease-related morbidity and mortality is hypertension. In the past decade, attention has been paid to increase females’ representation. The aim of this study is to investigate whether the representation of females and presentation of sex-stratified data in studies investigating the effect of antihypertensive drugs has increased over the past decades. Methods: After systematically searching PubMed and Embase for studies evaluating the effect of the five major antihypertensive medication groups until May 2020, a scoping review was performed. The primary outcome was the proportion of included females. The secondary outcome was whether sex stratification was performed. Results: The search resulted in 73,867 articles. After the selection progress, 2046 studies were included for further analysis. These studies included 1,348,172 adults with a mean percentage of females participating of 38.1%. Female participation in antihypertensive studies showed an increase each year by 0.2% (95% CI 0.36–0.52), p < 0.01). Only 75 (3.7%) studies performed sex stratification, and this was the highest between 2011 and 2020 (7.2%). Conclusion: Female participation showed a slight increase in the past decade but is still underrepresented compared to males. As data are infrequently sex-stratified, more attention is needed to possible sex-related differences in treatment effects to different antihypertensive compounds.

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 hypertensives.

Cardiovascular disease (CVD) is the number one cause of death worldwide, with hypertension as the leading risk factor for both sexes. As sex may affect responsiveness to antihypertensive compounds, guidelines for CVD prevention might necessitate divergence between females and males. To this end, we studied the effectiveness of calcium channel blockers (CCB) on blood pressure (BP), heart rate (HR) and cardiac function between sexes. We performed a systematic review and meta-analysis on studies on CCB from inception to May 2020. Studies had to present both baseline and follow-up measurements of the interested outcome variables of interest and present data in a sex-stratified manner. Mean differences were calculated using a random-effects model. In total, 38 studies with 8202 participants were used for this review. In females as compared to males, systolic BP decreased by −27.6 mmHg (95%CI −36.4; −18.8) (−17.1% (95%CI −22.5;−11.6)) versus −14.4 mmHg (95%CI −19.0; −9.9) (−9.8% (95%CI −12.9;−6.7)) (between-sex difference p < 0.01), diastolic BP decreased by −14.1 (95%CI −18.8; −9.3) (−15.2%(95%CI −20.3;−10.1)) versus −10.6 mmHg (95%CI −14.0; −7.3) (−11.2% (95%CI −14.8;−7.7)) (between-sex difference p = 0.24). HR decreased by −1.8 bpm (95%CI −2.5; −1.2) (−2.5% (95%CI −3.4; −1.6)) in females compared to no change in males (0.3 bpm (95% CI −1.2; 1.8)) (between-sex difference p = 0.01). In conclusion, CCB lowers BP in both sexes, but the observed effect is larger in females as compared to males.

Background Hypertension is one of the leading global risk factors for cardiovascular disease-related morbidity and mortality. Females have historically been underrepresented in clinical trials resulting in presumed sex-related disparities in antihypertensive treatment effects. The past decade, widespread attention has been paid to this shortcoming aiming at increasing females' representation in clinical trials. Purpose To investigate whether in studies investigating the effect of antihypertensive drugs 1) the representation of females and 2) presentation of sex-stratified data has increased over the past decades. Methods We performed a scoping review after systematically searching PubMed and Embase for studies evaluating the effects of the five major groups of antihypertensive medication from inception (1945) until May 2020. The review was registered in Prospero database. Studies were only included if they 1) investigated one class of the five main groups of antihypertensive medications (beta-blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, and diuretics, 2) human studies, 3) investigated adults ≥18 years of age, 4) were written in English or Dutch. We excluded articles if 1) only abstract was available and full report was not found, 2) unsuitable study design, 3) no reference group included, 4) outcome not related to cardiovascular health, 5) no registration of specific dose and duration information. The primary outcome was the proportion of included females over time, stratified per decade. The secondary outcome was whether sex-stratification was reported. Linear regression analysis with beta coefficient (β) and 95% CI was performed to explore the associations between the percentage of females included in the studies over time. Results The search strategy resulted in 73,867 potential articles. After study selection based on title/abstract and full text, 2,079 original studies were eligible for our study. These included 1,395,264 adults of which the mean percentage of females participating in all included studies was 27.9% (Figure 1, Table 1). The percentage of females participating in antihypertensive studies showed a slight increase each year by 0.4% (95% CI 0.36–0.53, P&lt;0.01). The yearly increase was the highest between 2001 and 2010 being 0.52% (95% CI 0.076–0.954) and in the most recent decade (between 2011 and 2020) 38.7% of included participants were female. Sex-stratification was performed in 76 (3.7%) studies and was the highest between 2011 and 2020 (7.3%). Conclusion Despite yearly increase in female participation in antihypertensive studies, females still only account for only one third of the study population. Moreover, less than 10% of studies report sex stratified data. Considering the global burden of hypertension, more differentiated sex-specific attention remains critically needed. Funding Acknowledgement Type of funding sources: None.