In real-world practice, women who are prescribed dabigatran for atrial fibrillation (AF) are usually given the lower dose of the drug, even though the higher dose appears to be more protective against stroke, according to Canadian database analysis published online Oct. 27 in Circulation: Cardiovascular Quality and Outcomes.
In RE-LY, the main randomized clinical trial showing that dabigatran is more effective at preventing stroke and provoked fewer bleeding episodes than warfarin, only 37% of the participants were women (N Engl J Med. 2009 Sep 17; 361[12]1139-51).This raises the question of whether the study’s results are truly applicable to women. In addition, the women in that trial showed plasma concentrations of dabigatran that were 30% higher than those in men, suggesting that the drug’s safety profile may differ between women and men. However, there was no mention of sex differences related to outcomes, said Meytal Avgil Tsadok, Ph.D., of the division of clinical epidemiology, McGill University Health Center, Montreal, and her associates.
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To examine sex-based differences in prescribing patterns in real-world practice, the investigators performed a population-based cohort study among 631,110 residents of Quebec who were discharged from the hospital with either a primary or a secondary diagnosis of AF during a 14-year period. They identified 15,918 dabigatran users and matched them for comorbidity, age at AF diagnosis, and date of first prescription for anticoagulants with 47,192 warfarin users (control subjects). The 31,786 women and 31,324 men participating in this study were followed for a median of 1.3 years (range, 0-3.2 years) for the development of stroke/TIA, bleeding events, or hospitalization for MI.
The researchers found that dabigatran use differed markedly between women and men. Men were prescribed the lower dose (110 mg) in nearly equal numbers with the higher dose (150 mg) of dabigatran, but women were prescribed the lower dose (64.8%) much more often than the higher dose (35.2%). In a further analysis of the data, women were much more likely than men to fill prescriptions of the lower dose (odds ratio, 1.35). This was true even though women, but not men, showed a trend toward a lower incidence of stroke when prescribed the higher dose of dabigatran, compared with warfarin.
These prescribing practices remained consistent even when the participants were categorized according to age. More women than men used low-dose dabigatran whether they were younger than 75 years of age (22.8% vs. 18.5%) or older than 75 years (83.5% vs. 76.0%). These findings show that, regardless of patient age or comorbidities, “women have 35% higher chances to be prescribed a lower dabigatran dose than men, although women have a higher baseline risk for stroke,” Dr. Tsadok and her associates said (Circ Cardiovasc Qual Outcomes. 2015 Oct 27 [doi: 10.1161/circoutcomes.114.001398]).
The reason for this discrepancy is not yet known. A similar pattern of prescribing was noted in a Danish population-based cohort study. It’s possible that clinicians perceive women as frailer patients than men, “so they tend to be more concerned about safety and, therefore, prescribe women with a lower dose, compromising efficacy,” the investigators said.
Their study was limited in that follow-up was relatively short at approximately 1 year. It is therefore possible that they underestimated the risks of stroke/TIA, bleeding events, or MI hospitalization, Dr. Tsadok and her associates added.
This study was supported by the Canadian Institutes of Health Research. Dr. Tsadok and her associates reported having no relevant financial disclosures.