“The ESC wants to raise awareness, among both cardiologists and the public, that women still are not receiving equal access to medical treatments and also are not being represented sufficiently in clinical trials,” says Marco Stramba Badiale, an ESC spokesman on women’s issues from IRCCS Istituto Auxologico Italiano (Milan, Italy). “The problem is that despite female gender being associated with worse CV outcomes there are still major misconceptions among both health professionals and the public that cardiovascular disease (CVD) isn’t as serious in women as men.”
Data from the World Health Organisation (WHO) show that CVD in Europe accounts for 55% of deaths in women compared to just 43% of deaths in men. While breast cancer - perhaps the most feared illnesses among women - is responsible for only 3% of female deaths. Moreover, recent data from the National Health and Nutrition Examination Surveys (NHANES) looking at tends in midlife coronary heart disease risk show over the past two decades the prevalence of myocardial infarction (MI) has increased in women aged 35 to 54 years, while declining in men of the same age.
“It’s very important that physicians are aware that coronary artery disease (CAD) is a frequent disease among women, that gets more common as they get older,” says Thomas Lüscher, editor of the EHJ, who has brought together a special issue exploring CV issues facing women.
The studies published in the themed issue raise particular concerns that women are being prescribed fewer drugs than men. “We were shocked to find that even after infarction - the most dramatic cardiac situation we envisage - there’s still a dramatic under-utilisation of drugs in women,” says Prof. Lüscher, from University Hospital Zurich (Switzerland). “These issues need to be urgently corrected to ensure that women get equal access to state of the art treatments as men.”
In the first EHJ study ¹, published online today, cardiologists from the University of Bologna (Bologna, Italy), and the University of Toronto (Toronto, Ontario, Canada), analysed the medical details of 4471 men and 2087 women who had experienced an acute coronary syndrome (heart attack) between 1999 and 2003. The details (which included 23 clinical variables) were recorded on the Canadian Registry of ACS I and I. Results show that women were less likely to:
- Receive beta-blocker: 75.76 % of women received beta blockers in comparison to 79.24% of men (P<0.01).
- Receive lipid-modifying agents: 56.37 % of women received lipid-modifying agents compared to 65.44% of men (P<0.0001).
- Receive angiotensin-converting enzyme (ACE) inhibitors – 55.52% of women received ACE inhibitors compared to 59.99% of men (P<0.01).
The authors led by Raffaele Bugiardini, from the University of Bologna (Bologna, Italy) say that the disparity appears to depend upon multiple factors related to patient age (women are more likely to be older with concerns about prescribing drugs in the elderly), congestive heart failure (women are more likely to develop heart failure during ACS and physicians are reluctant to initiate beta blockers in patients with congestive heart failure), and the physician’s decision to undertake catheterization (women are less frequently referred for cardiac catheterization than men).
However, after adjusting for age, the presence of congestive heart failure, and whether or not the patient underwent catheterization, women still received fewer ACE-inhibitors and lipid lowering drugs than men. “We’ve known for years that women are treated differently from men, but now this study shifts the philosophy and starts to explain why,” says Bugiardini.
In the second study between 2006 and 2008, Nina Johnston and colleagues ² from Uppsala University Hospital and Center for Gender Medicine, Karolinska Institutet, (Stockholm, Sweden) analysed use of cardiovascular medications and diagnostic coronary angiography in 7195 men and 5005 women with suspected coronary artery disease (CAD) after experiencing chest pain. The patients were all registered in the Swedish Coronary Angiography and Angioplasty Register (SCAAR).
Results showed that prior to undergoing angiography 83% of women had been prescribed aspirin in comparison to 86.1 % of men (P=0.001).
The study also showed that in the youngest age group (those aged under 59 years) 78.8% of women who underwent angiography were found to have normal/ non-significant CAD in comparison to 42.3% of men (P<0.001), and furthermore that 18.2% of men were diagnosed with left main or three vessel disease compared to 4.2% of women (P<0.001). This, say the authors, underlines the difficulty faced by clinicians in diagnosing CAD in women.
In the print version of the EHJ (to be published later in the year) the two papers will be accompanied by an editorial by Noel Bairey Merz, from Cedar-Sinai Heart Institute (California, USA). Merz is an international expert on microvascular coronary dysfunction, a condition where dysfunction of the artery’s ability to dilate causes narrowing and reduced oxygen flow. The condition, Merz believes, affects women far more frequently than men and may explain why it is more difficult to make a diagnosis in women.
“We estimate that microvascular coronary dysfunction accounts for a third to one half of heart disease in mid-life women, but unlike obstructive CAD, it doesn’t show up on an angiogram making it more difficult to diagnose,” explains Merz.
The ESC, who has been campaigning for some time for the inclusion of greater numbers of women in clinical trials for CVD, are calling upon the European Medicines Agency (EMA) to make the fair representation of women in clinical trials a requirement for the licensing of all pharmaceutical agents.
The need for more women to be involved in trials is supported by Work Package 6 of the EuroHeart project, a study that was undertaken by the ESC in conjunction with the European Heart Network to assess the representation of women in clinical trials. The study, which reviewed 62 randomised clinical trials that had been published since 2006 found that out of 389,891 participants, 127.716 (33.5%) were women, and that additionally only 31 out of the 62 trials (50%) reported their analysis by gender.
“It’s very important that data concerning women is analysed separately because there are often differences in the pharmacodynamics, pharmacokinetics and physiology in comparison to men, making it possible that the efficacy of drugs might be completely different in women,” says Stramba-Badiale.