Sex Differences in Oral Anticoagulation and Outcomes of Stroke and Intracranial Bleeding in Newly Diagnosed Atrial Fibrillation

Abstract

Background Female sex is an independent predictor of stroke in patients with atrial fibrillation (AF). Older data suggest undertreatment with anticoagulation among women compared with men. However, it is unknown if novel therapies and updated guidelines have impacted sex differences in AF treatment and outcomes. Methods and Results We performed a retrospective cohort study of 2.3 million women and men with a new diagnosis of AF and CHA 2 DS 2 ‐VASc ≥2 from Marketscan US commercial claims data from 2008 to 2015 to determine whether women with AF remain undertreated and whether this difference mediates observed differences in outcomes. There were 358 649 patients with newly diagnosed AF (43% women). Compared with men, women were older, with higher CHA 2 DS 2 ‐VASc scores, and higher comorbidity burden ( P <0.0001 for all). Oral anticoagulation‐eligible women with CHA 2 DS 2 ‐VASc scores ≥2 were more likely to not receive anticoagulation (50.0% women versus 43.9% men). Women, compared with men, had a higher risk of ischemic stroke (adjusted hazard ratio [aHR], 1.27; 95% CI, 1.21–1.32; P <0.0001) and hospitalization (aHR, 1.06; 95% CI, 1.05–1.07, P <0.0001) but had a lower risk of intracranial bleeding (aHR, 0.91; 95% CI, 0.83–0.99, P =0.03). In mediation analysis, nonreceipt of oral anticoagulation partially mediated the observed increased risk of stroke and decreased risk of intracranial bleeding in women. Conclusions In the care of newly diagnosed AF in the United States, women, compared with men, are less likely to receive oral anticoagulation. This appears to mediate the increased risk of both stroke and hospitalization but also appears to mediate lower observed intracranial bleeding risk.

Lack of Sex Disparity in Oral Anticoagulation in Atrial Fibrillation Patients Presenting with Ischemic Stroke in a Rural Population

“…In contrast, recent studies have identified potential sex disparities in OAC undertreatment (Supplemental Table S2). Retrospectives studies have found lower odds of OAC initiation and an increased likelihood of undertreatment among high-risk female patients with Medicare and commercial insurance [7,8]. Similarly, a study using the PINNACLE National Cardiovascular Data Registry found that women had a higher risk of undertreatment across all levels of the CHA 2 DS 2 -VASc scores [9], while a study from the Euro Observational Research Programme Pilot survey on atrial fibrillation (EORP-AF) reported that more women with CHA 2 DS 2 -VASc ≥ 2 received OAC than men [13].…”

“…However, in our previous study, we found similar undertreatment rates using CHA 2 DS 2 -VASc and CHADS 2 scores [14], and our results in this study are consistent even when using CHADS 2 for risk stratification. Other limitations include the lack of a complete HAS-BLED score (Supplemental Results R2), used by clinicians to identify patients at risk for bleeding [3,6,28] and to potentially examine sex disparities [7][8][9]11,13,19].…”

“…Despite the AHA/ACC/HRS guidelines for the management of patients with atrial fibrillation [3], some studies have suggested that women have a higher risk of OAC undertreatment than men [7][8][9][10], while others have reported no significant differences [11,12].…”

Women and atrial fibrillation

“…The oral anticoagulation‐eligible women were not as likely to receive anticoagulation; 50.0% women versus 43.9% men did not received anticoagulation. A mediation analysis revealed that not receiving oral anticoagulation partially mediated the observed increased risk of stroke but also decreased risk of intracranial bleeding in women 51 . In the global FIELD (GARFIELD)‐AF anticoagulant registry, there was no significant difference in the overall rate of anticoagulant use found between the sexes (61% for both) 52…”

Cerebrovascular disease in women

“…82 Despite this, studies have shown that women are significantly less likely than men to use any oral anticoagulant at all levels of thromboembolic risk. 83,84 Higher rates of bleeding in women taking warfarin, provider bias, concerns about frailty and higher fall risk, and older age at the time of stroke may all be potential reasons for this discrepancy. No sex differences in safety or efficacy have been reported in the multiple RCTs of novel oral anticoagulants (NOACs) in AF and stroke prevention.…”