Sex differences in atrial fibrillation

In their review, Rienstra and Van Gelder summarize their findings from the Rate Control Versus Electrical Cardioversion (RACE) study. In this study, the difference between treatment approaches in patients with atrial fibrillation was examined. Specifically, strategies of heart rate control were compared with restoration and maintenance of sinus rhythm. A combined end point of cardiovascular mortality, heart failure, thromboembolic complications, bleeding, severe adverse effects of antiarrhythmic drugs, and pacemaker implantation was evaluated. The results showed no difference between treatment strategies. However, the investigators found a significant difference between treatment strategies among women enrolled in the trial. Women in the rhythm control arm experienced an end point 33% of the time compared with only 11% of women in the rate control arm.

Several studies have shown sex differences in atrial fibrillation. The Framingham data showed increased mortality among women with atrial fibrillation.¹ In addition, Fang and colleagues showed that women with atrial fibrillation are at higher risk for thromboembolic events than are men.² Contrary to these studies, however, the Atrial Fibrillation Follow-up Investigation of Rhythm Man­agement (AFFIRM) study actually showed that male sex was associated with a higher risk of noncardiovascular death (hazard ratio = 1.45).³ Sex differences also exist regarding the safety of antiarrhythmic agents used to treat atrial fibrillation. Women have been noted to be more prone to develop torsades de pointes while being treated with antiarrhythmic drugs.⁴

Rienstra and Van Gelder concluded that a heart rate control strategy should be the treatment of choice for women and that a rhythm control strategy was not beneficial. It is important to note that this study, like the AFFIRM trial, compared 2 treatment strategies. These trials did not compare sinus rhythm with atrial fibrillation. It is striking that only 35% of the female patients in the rhythm control arm actually achieved sinus rhythm. In the AFFIRM trial, the prevalence of sinus rhythm at 1, 3, and 5 years was 82.4%, 73.3%, and 62.6%, respectively.⁵ In the rate control arm, over 80% of patients achieved adequate rate control. The low rate of success in achieving and maintaining sinus rhythm is consistent with the relatively low efficacy of modern antiarrhythmic agents.

In a study assessing the effect of sinus rhythm on the outcomes of patients in the AFFIRM trial, it was noted that the presence of sinus rhythm was associated with improved survival.⁶ A similar finding was reported in the Danish Investigators of Arrhythmia and Mortality on Dofetilide (DIAMOND) study, which examined the efficacy of dofetilide (Tikosyn) for the treatment of patients with reduced left ventricular ejection fraction and atrial fibrillation/flutter.⁷ It would be interesting to know if the increase in the morbidity of women would still occur if the success rate in achieving sinus rhythm was higher in this trial. If we rely on current antiarrhythmic agents, the question is moot, of course. However, there are currently nonpharmacologic treatments for symptomatic atrial fibrillation that promise to be more effective than current antiarrhythmic drugs. Pappone and colleagues compared treatment with antiarrhythmic agents versus catheter ablation in patients with atrial fibrillation.⁸ Patients who underwent catheter ablation had improvements in mortality, morbidity, and quality of life compared with those who took antiarrhythmic agents. This may be attributed to the high success rate of catheter ablation techniques compared with antiarrhythmic drugs.

In summary, the authors of this article point out an important difference between men and women with atrial fibrillation. Women appear to have worse outcomes when a treatment strategy of rhythm control is chosen. Additional sex differences in atrial fibrillation have been noted in other studies. However, we do not know if this same result would be seen if we were more successful in achieving the goals of our treatment strategy (ie, restoration and maintenance of sinus rhythm). There are data to suggest that sinus rhythm is associated with improved survival. Perhaps more effective treatments, such as catheter ablation techniques, will allow us to actually maintain sinus rhythm in our patients.