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10. Sex Differences in Patients With AF

Recognition of sex differences offers an opportunity to improve outcomes in women with AF.[659]

10.1 Epidemiology and pathophysiology

Age and sex are the two most powerful predictors of incident AF. Although the prevalence of AF doubles with each decade of age (increasing from 1%-4% at 60 years to 6%-15% at 80 years), male sex is associated with a 1.5-fold risk of AF, even after adjusting for age and predisposing conditions. Although the age-adjusted prevalence of AF is consistently observed to be higher in men (eg, a sex-based prevalence of 9.2% for women vs 15.0% for men in a community-based, randomized, controlled AF screening study performed in Sweden)[31],[85] the absolute number of female patients with AF exceeds the number of male patients with AF because of the longer life span of female patients. Although the exact mechanism responsible for the reported sex-related differences in AF remains inadequately understood, several theories have been suggested. First, anthropomorphic differences between the sexes result in a larger LA dimension and volume in male patients.[660],[661] Second, female patients with AF have been shown to have a relatively greater burden of atrial fibrosis using delayed-enhancement MRI.[662] Third, male patients with AF have greater expression of repolarizing ion channel subunits, which could favour reentry.[660],[663] Fourth, the contribution of sex hormones has been explored in several studies, with testosterone deficiency having been linked to increased atrial arrhythmogenicity[664]; progesterone associated with shortened action potentials[665]; and estrogen has been postulated to play a central role in arrhythmogenesis due to prolongation in conduction time, action potential duration, and the atrial effective refractory period.[666]

10.2 Presentation

Female patients with AF are more likely to have underlying hypertension and valvular disease, whereas male patients with AF are more likely to have CAD and abnormal LV function. Female patients with AF report more atypical symptoms, with a relatively greater symptom burden and lower QOL compared with male patients.[667],[668] As a result, women are more likely to seek care for AF symptoms and are more likely to experience depression related to AF.[669]

10.3 Outcomes

Important sex-specific differences in cardiovascular outcomes have been described. AF in female patients is associated with a greater all-cause mortality relative to male patients (RR, 1.12; 95% CI, 1.07-1.17).[670] Compared with male patients with AF, strokes experienced by female patients tend to be larger, and are associated with poorer functional outcomes and greater need for institutionalization.[671]

10.4 Stroke prevention

Sex-specific differences in antithrombotic therapy have been observed: female patients with AF are more likely to be prescribed antiplatelet agents; when OACs are prescribed, they are more likely to receive a DOAC and, are more likely to be inappropriately prescribed the lower approved dose.[672][675] In terms of efficacy, female patients with AF have a greater residual risk of stroke despite VKA therapy, which might reflect sex-specific differences in VKA metabolism or underlying risk factor control.[676],[677] Although no sex-specific difference in DOAC efficacy has been observed, there is a significant reduction in major and clinically-relevant nonmajor bleeding in female patients with AF treated with a DOAC.[21][23],[25],[52],[677]

10.5 Rate and rhythm management

Female patients with AF are more likely to receive rate control, compared with male patients with AF.[678],[679] In those who receive rhythm control, female patients with AF are preferentially managed with pharmacologic antiarrhythmic therapy, and are less likely to undergo ablation (OR, 0.5-0.8 compared with men).[680],[681] Moreover, female patients who do undergo ablation tend to be older, have more comorbidities, have more advanced AF (eg, longer duration of AF, more likely to be persistent), and show that treatment with a larger number of antiarrhythmic agents have failed.[395],[663],[682],[683] Despite their more complex clinical profile before ablation, female patients who undergo ablation have comparable acute and longer-term success rates compared with male patients.[668],[682],[683]


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