Men and women may react differently to medication for cardiovascular disease. Women stop taking their medication due to adverse effects more often than men and they also have different adverse effects from the same medication than men. The optimum dosage for heart failure medication may also be lower for women than for men. On Thursday, September 2, researcher Sophie Bots of UMC Utrecht obtained her doctoral degree for her study of the added value of regular healthcare data in research into male-female differences.

Women are different from men. Nevertheless, in scientific research into cardiovascular disease the results for men and women are often presented together. “There is a lack of gender-specific knowledge, such as on the optimum treatment of women and men with cardiovascular disease,” says Sophie. “This is remarkable, because women and men may react differently to medication. I studied whether healthcare data, comprising 110,000 electronic patient records, offer more insight into male-female differences relating to the safety and effectiveness of medication that is commonly prescribed for cardiovascular disease.”

Different adverse effects in women
The healthcare data show that women stop taking their medication due to adverse effects more often than men. This differs per medicine and varies from 11% to 50% more adverse effects in women, after correction for the number of prescriptions. Women also report other adverse effects for the same drugs than men. Women suffer more often from headache, dizziness, allergic reactions and abdominal pain, while men have heart or kidney complaints more often. “The risk of adverse effects from medication for cardiovascular disease differs between men and women. This requires gender-specific information about the adverse effects of medication, which physicians can use in their consultation with the patient,” concludes Sophie.

Optimum dosage
The healthcare data also show that optimum dosage of heart failure medication may be lower for women than for men. In practice, women are more often given lower doses, which appears to have a maximum beneficial effect on the risk of death. Current treatment guidelines prescribe the same dosage for men and women. “This finding suggests that women may be better off with a lower dose. This should be properly investigated in a clinical trial, because while healthcare data do provide a direction, there are a number of snags. In any case, the study underlines that reporting gender-specific doses for medication may result in better care for patients with heart failure.”

Stronger effect from statins
Sophie then looked at the male-female differences in the effectiveness of statins (cholesterol-lowering drugs). Although the effectiveness of these agents has been proven several times, they are prescribed to women less often and in lower doses. The study shows that statins lower the risk of death in both women and men and that this effect may be even stronger in women (34% lower risk of death compared to 11% in men). A higher dose has a stronger effect than a lower dose, but the difference is marginal. “This research confirms that statins are also effective for women and that even a low dose can make a big difference. Hopefully this will eliminate any remaining doubts from both treating physicians and women eligible for statin treatment,” Sophie says.

Regular healthcare data as first go-to for unanswered questions
The healthcare data provide added value for answering unanswered questions about gender differences in cardiovascular disease. This is especially relevant for unanswered questions about which hardly any information is currently available, such as gender differences relating to the safety and efficacy of medication. “These data show where male-female differences can occur and thus identify topics that need more research. This can inform the scientific research agenda about which new clinical trials and cohort studies are needed for follow-up research.”

The study was co-funded by the Dutch Heart Foundation, the Netherlands Organisation for Health Research and Development, DCVA, ERC and Friends of UMC Utrecht