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1 Table S1 Sex- specific differences in rate- control and rhythm- control strategies in observational studies Study region Study period Total sample size Sex- specific results Ozcan (2001) 1 Mayo Clinic, USA July 1990 Dec (47%) No sex- specific differences in mortality Galperin (2003) 2 Patients with symptomatic paroxysmal or chronic AF, refractory to pharmaceutical rate or rhythm control, who underwent atrioventricular- node ablation and implantation of permanent pacemaker Single- centre in NS 141 (32%) No sex- specific differences in maintenance of sinus rhythm Argentina Patients with persistent AF lasting for 2 months undergoing electrical cardioversion during amiodarone treatment

2 Essebag (2007) 3 Dagres (2007) 4 Euro Heart Survey Study region Study period 17 centres in USA and Enrolment started Canada 1997 Patients enrolled after first ECG- confirmed AF episode 182 centres from 35 ESC countries Patients with AF on ECG or Holter recording at ambulatory visit or hospitalization during admission or within preceding 12 months Enrolment during Sep 2003 July 2004 Total sample size Sex- specific results 973 (40%) Univariate analyses only Women were less likely to be receiving amiodarone at follow- up (19.5% vs 26.2%; P = 0.02) Women were more likely to be receiving digoxin at follow- up (46.2% vs 39.3%; P = 0.03) Women had significantly increased risk of pacemaker insertion after amiodarone therapy (HR 4.69, P = 0.02). Men did not have an increased risk 5,333 (42%) Univariate analyses only Women less likely to receive TEE to detect left atrial thrombus (73% vs 81%; P = ) Women more likely to receive rate over rhythm control compared with men when experiencing atypical symptoms (P <0.001) Women: 45% rhythm Men: 59% rhythm 44% rate 33% rate Women more likely to receive rate over rhythm control compared to men when asymptomatic (P <0.001) Women: 36% rhythm Men: 46% rhythm 49% rate 39% rate Women less likely to receive electrical cardioversion (22% vs 28%; P <0.001) and catheter ablation (3% vs 6%; P <0.001) Women who underwent rhythm control had higher rate of stroke (5.0% vs 1.2%; P = 0.006)

3 Gronberg (2013) 5 Airaksinen (2013) 6 FinCV Sabouret (2014) 7 Study region Emergency clinics at two university hospitals and one central hospital in Finland Patients aged 18 years presenting to emergency departments with AF <48 h who underwent pharmacological or electrical cardioversion France, nationwide Study period Total sample size Sex- specific results ,143 (36%) Female sex was an independent risk factor for bradyarrhythmia after cardioversion in multivariable analysis (OR 2.5, 95% CI , P = 0.004) July 2010 June ,623 (41%) Female sex was an independent risk factor for thromboembolic complications after cardioversion when no periprocedural anticoagulation prophylaxis was used in multivariable analysis (OR 2.1, 95% CI ) No significant sex- specific difference in antiarrhythmic drug use French medical and prescriptions files database from GPs Patients with AF, aged 18 years with at least one GP consultation

4 Lip (2015) 8 EORP- AF Study region 67 centres in nine European countries Patients with AF on ECG or Holter recording within preceding 12 months Study period Enrolment during Feb 2012 Mar 2013 Total sample size Sex- specific results 3,119 (39.4%) Univariate analyses only Women less likely to receive TEE (9.7% vs 12.4%; P = ) Women were more likely to receive pharmacological cardioversion (28.2% vs 22.4%; P = ) and less likely to receive electrical cardioversion (18.9% vs 25.5%; P <0.0001). No differences in use of catheter ablation Women more likely to receive rate over rhythm control compared with men when experiencing typical symptoms (P = 0.002) Women: 11% rhythm Men: 15% rhythm 33% rate 26% rate Bhave (2015) 9 USA, nationwide Data from ,941 (60%) Women were more likely to be receiving digoxin (25.0% vs 19.8%; P = ) Multivariable adjusted analyses Centers for Medicare and Medicaid data Women were less likely to have an outpatient clinic visit with an electrophysiologist (14.6% vs 18.1%; HR 0.92, P <0.001) Patients with first AF encounter between 2010 and 2011, aged >65 years Women were less likely to have catheter ablation (0.6% vs 1.3%; HR 0.65, P <0.001) Women received more rate- control (67.0% vs 63.1%; HR 1.16, P <0.001) or rhythm- control (HR 1.04, P <0.001) medications

5 Mochalina (2015) 10 Alegret (2015) 11 Study region Study period Single centre, Sweden Patients aged 18 years with recent- onset AF with symptoms for <48 h treated with intravenous vernakalant 67 centres in Spain Total sample size Sex- specific results Dec 2010 Dec (39%) Conversion to sinus rhythm was more likely in women in univariate analysis (80% vs 58%; P = 0.024) Feb 2012 June (24%) Univariate analyses only CARDIOVERSE Patients aged >18 years with persistent AF (>7 days) who underwent elective electrical cardioversion Women were significantly less likely to undergo electrical cardioversion (24% vs 76%; P <0.001) No sex- specific differences in the rate of successful cardioversion and maintenance of sinus rhythm at 1 month and 1 year Smaller proportion of women underwent electrical cardioversion compared with the previous decade (P <0.001) AF, atrial fibrillation; ECG, electrocardiogram; GP, general practitioner; TEE, transoesophageal echocardiography. 1. Ozcan, C. et al. Long- term survival after ablation of the atrioventricular node and implantation of a permanent pacemaker in patients with atrial fibrillation. N. Engl. J. Med. 344, (2001). 2. Galperin, J. et al. Pharmacologic reversion of persistent atrial fibrillation with amiodarone predicts long- term sinus rhythm maintenance. J. Cardiovasc. Pharmacol. Ther. 8, (2003). 3. Essebag, V. et al. Sex differences in the relationship between amiodarone use and the need for permanent pacing in patients with atrial fibrillation. Arch. Intern. Med. 167, (2007). 4. Dagres, N. et al. Gender- related differences in presentation, treatment, and outcome of patients with atrial fibrillation in Europe: a report from the Euro Heart Survey on Atrial Fibrillation. J. Am. Coll. Cardiol. 49, (2007). 5. Gronberg, T. et al. Arrhythmic complications after electrical cardioversion of acute atrial fibrillation: the FinCV study. Europace 15, (2013).

6 6. Airaksinen, K. E. et al. Thromboembolic complications after cardioversion of acute atrial fibrillation: the FinCV (Finnish CardioVersion) study. J. Am. Coll. Cardiol. 62, (2013). 7. Sabouret, P. et al. Sex differences in stroke prevention in atrial fibrillation in French primary care. Results of the AFIGP (Atrial Fibrillation In General Practice) database. Clin. Res. Cardiol. 103, (2014). 8. Lip, G. Y. et al. Sex- related differences in presentation, treatment, and outcome of patients with atrial fibrillation in Europe: a report from the Euro Observational Research Programme Pilot survey on Atrial Fibrillation. Europace 17, (2015). 9. Bhave, P. D., Lu, X., Girotra, S., Kamel, H. & Vaughan Sarrazin, M. S. Race- and sex- related differences in care for patients newly diagnosed with atrial fibrillation. Heart Rhythm 12, (2015). 10. Mochalina, N. et al. Predictors of successful cardioversion with vernakalant in patients with recent- onset atrial fibrillation. Ann. Noninvasive Electrocardiol. 20, (2015). 11. Alegret, J. M. et al. Gender differences in patients with atrial fibrillation undergoing electrical cardioversion. J. Womens Health (Larchmt) 24, (2015).