Women are substantially underrepresented in clinical trials used to formulate gender-specific guidelines for the prevention of cardiovascular disease, a new US analysis has found.

A research team led by Dr Chiara Melloni from Duke University Medical Center in Durham, North Carolina reviewed 156 randomised clinical trials (RCTs) cited in the American Heart Association’s (AHA) 2007 update of its guidelines for cardiovascular disease prevention. The researchers’ conclusions were published in a themed issue of the journal Circulation: Cardiovascular Quality and Outcomes.

While cardiovascular disease (CVD) is the primary cause of death among women, there remains a “concerning gap” in the knowledge, understanding and general awareness of the condition in this population, the authors point out.

Evidence-based medicine for the prevention and treatment of CVD is guided largely by the results of RCTs. Moreover, the “demonstration by many studies of a sex-specific response to certain cardiovascular therapies underscores the importance of adequate representation in clinical trials populations”, Melloni et al say.

Noting that the AHA’s 2007 guidelines “drew heavily” on the results of RCTs, Melloni’s team set out to determine how well women were represented in these trials. Among the 156 studies cited in the guidelines, both women and men were represented in 135 or 86.5% of the total, 20 trials enrolled only men, and just one trial only women.

While the proportion of women enrolled in the RCTs increased significantly over time, from 9% in 1970 to 41% in 2006, overall women accounted for only 30% of the study population for all of the trials combined. Moreover, sex-specific results were reported in just 31% of primary trial publications.

Representation of women was most pronounced in RCTs for hypertension (44%), diabetes (40%) and stroke (38%), while the lowest levels of representation were seen in trials for heart failure (29%), coronary artery disease (25%) and hyperlipidaemia (28%).

As a point of comparison, Melloni et al observe, women make up 53% of the total US population with hypertension, 50% of people with diabetes, 51% of heart failure cases, 49% of hyperlipidaemia cases and 46% of people with coronary artery disease.

The reasons for the relatively low enrolment of women in RCTs for cardiovascular disease “are difficult to ascertain, thus undermining attempts to develop specific corrective actions”, the researchers comment.

“In addition to further study to discern the underpinnings of and obviate disparities in female representation in clinical trials, a plan for adequate representation of women and sex-specific results should be a key requirement in the design and publication of RCTs that will serve as part of the evidence base for treatment recommendations,” they suggest.