The underrepresentation of females in antihypertensive medication over the years: a scoping review
Authors: Mohseni-Alsalhi Z , Vesseur M A M , Laven S A J S , Vaes E W P , Wilmes N , Meijs D A M , Van Luik E M , Dikovec C J R , Wiesenberg J , Almutairi M F , Janssen E B N J , De Haas S , Spaanderman M E A , Ghossein-Doha C 
Published: October 2022

Abstract

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.