DOACs most beneficial for women with AFib

Non-vitamin K antagonist oral anticoagulants may be even more effective for treating women with atrial fibrillation (AFib) than men, suggests a real-world study from Hong Kong published in the Journal of the American College of Cardiology.

Previous data show that men have a great risk of AFib, but women with AFib have a higher risk of stroke, even when using warfarin. But sex-specific comparisons of newer direct oral anticoagulants (DOACs) versus warfarin are limited, wrote lead author Sharon W.Y. Law, MPharm, and colleagues.

The researchers propensity-score matched men and women separately, pairing DOAC users with warfarin users based on similar age, comorbidity burdens, number of inpatient visits and current medication use. Nearly 5,000 members of each sex with nonvalvular AFib were included in the analysis.

Compared with warfarin users, women on DOACs experienced relative reductions of 84 percent and 45 percent for intracranial hemorrhage (ICH) and all-cause mortality, respectively. Men didn’t show significant differences in these outcomes by treatment type, and both sexes experienced similar rates of the primary composite outcome of stroke or systemic embolism (SSE).  

Notably, even among women with well-control warfarin use—defined as time in therapeutic range of 60 percent or more—the risk of ICH was reduced by 87 percent with DOACs.

“Our study using Asian clinical data showed that DOAC use was associated with a lower risk of ICH and all-cause mortality when compared with warfarin users in women only,” Law et al. wrote. “Although the result was not statistically significant, women on DOACs had a trend for being more protected from SSE when compared with warfarin.”

The researchers said their results highlight the need for more women to be included in cardiovascular trials, including those evaluating anticoagulation strategies. Women comprised just 25 percent of participants in major trials of warfarin, they said. Even though the proportion has increased to about 40 percent in more recent trials of DOACs, the studies weren’t designed to analyze sex-specific results.

“Sex-specific analysis is particularly important as women appear to have different utilization patterns and metabolism of anticoagulants when compared with men,” Law and colleagues wrote.

Limitations of the study include the lack of direct comparison for each type of DOAC (apixaban, rivaroxaban and dabigatran). They were all grouped together to provide enough statistical power in the comparison versus warfarin. Also, adherence to DOACs couldn’t be assessed, and the study population was predominantly Asian, limiting generalizability to other groups.

In a related editorial, two Italian cardiologists said the published studies evaluating gender-specific differences in DOAC effectiveness have been inconclusive and in contrast with one another—possibly as a result of different study designs and inclusion criteria.

They said hormonal changes based on the normal menstrual cycle, menopause, contraceptive use and hormone replacement therapy could affect women’s coagulation factors. Also, bleeding risk may be heightened in women with lower body weights who are assigned the same dose of medications as larger men.

“In any case, the main finding from the study by Law et al., as well as from other studies, points to the existence of sex difference in thrombotic and hemorrhagic risk and in the response to anticoagulants,” wrote Giulia Renda, MD, PhD, and Raffaele De Caterina, MD, PhD, both with D'Annunzio University of Chieti.

“This may imply different efficacy and safety profile of the DOACs in patients with (AFib) according to sex, which should be confirmed in further studies.”