Reynolds 2018.

Study characteristics
Methods	Study design: prospective, multicentre, randomised, parallel‐group, open‐label clinical trial Study grouping: parallel group Total duration of the study: December 2015 to May 2018 Duration of follow‐up: completed follow‐up through either 30 days or the occurrence of a study endpoint Number of study centres and location: 18 study sites in the US
Participants	Inclusion criteria: for prospective apixaban cohort were aged ≥ 18 years and scheduled for catheter ablation for the treatment of non‐valvular AF, with a planned continuation of OAC for minimum 1 month after the procedure Exclusion criteria: people with mechanical heart valves, advanced hepatic or renal (CrCl < 15 mL/minute or on dialysis) dysfunction, ongoing or planned dual antiplatelet therapy, history of stroke or TIA within 6 months, history of prior intracranial bleeding, significant baseline anaemia or thrombocytopenia Total number of participants: 306 Number of randomised participants: 300 Number lost to follow‐up/withdrawn: 5 Number of analysed participants: 295 Number of participants in each treatment group: minimally interrupted apixaban: 145; uninterrupted apixaban: 150 Baseline characteristics Interrupted anticoagulation Age, years, mean: 64.3 (SD 10.3) Men (%): 66.9 CHA2DS2‐VASc score, mean: 2.4 (SD 1.6) HAS‐BLED score, mean: 1.1 (SD 0.8) Type of AF, (%): persistent < 1 year: 35.9 persistent ≥ 1 year: 1.4 paroxysmal: 62.8 Comorbidities, (%): diabetes mellitus: 23.5 hypertension: 70.3 prior stroke: 2.8 heart failure: 9.0 CAD: 17.3 chronic kidney disease: 5.6 valvular disease: 9.9 COPD: 10.4 sleep apnoea: 33.3 Concomitant medications, (%): aspirin: 17.2 other antiplatelet drug: 2.1 Uninterrupted anticoagulation Age, years, mean: 62.8 (SD 9.9) Men (%): 67.3 CHA2DS2‐VASc score, mean: 2.2 (SD 1.6) HAS‐BLED score, mean: 1.0 (SD 0.9) Type of AF, (%): persistent < 1 year: 31.3 persistent ≥ 1 year: 2.0 paroxysmal: 66.7 Comorbidities, (%): diabetes mellitus: 22.0 hypertension: 68.0 prior stroke: 4.0 heart failure: 14.1 CAD: 28.2 chronic kidney disease: 3.3 valvular disease: 10.1 COPD: 8.7 sleep apnoea: 30.8 Concomitant medications (%): aspirin: 28.0 other antiplatelet drug: 0.7 Group differences: no significant differences in demographic or clinical characteristics between groups
Interventions	Periprocedural anticoagulation Anticoagulants used: apixaban Dose: 5 mg twice daily or 2.5 mg twice daily Duration of anticoagulant therapy in trial: minimum of 21 days before the planned ablation procedure, taken either as pre‐existing therapy, or newly initiated upon study entry.  Participants randomised 3 days before procedure Intensity of anticoagulation or dose adjustment: apixaban 2.5 mg was also used Adherence to anticoagulant treatment: treatment compliance was assessed by participant self‐report Time of interruption of the anticoagulants prior to procedure: 1 dose of apixaban (morning dose) on the day of ablation (minimally interrupted) was held Heparin therapy (intra‐procedural or as bridge therapy): none used Time and strategy of resumption of the interrupted OAC after procedure: in the evening of the procedure day, participants resumed apixaban at their usual dose (usually 5 mg) if there had been no prohibitive complications. OAC was then continued for ≥ 1 month postprocedure, when the final study visit was scheduled TOE: reported that TOE was not required Ablation procedure Type of ablation: PVI Ablation energy source: cryoballoon ablation, or force‐sensing radiofrequency ablation Intraprocedural anticoagulant Sites were instructed to administer a heparin bolus before transseptal puncture and to maintain a target ACT > 300 seconds
Outcomes	Endpoints were assessed from the time of randomisation for 30 days Primary safety endpoint Clinically significant bleeding, defined as any event meeting BARC criteria ≥ 2 Primary efficacy endpoint Non‐haemorrhagic stroke or systemic embolism Secondary endpoints Composite of stroke or systemic embolism or major bleeding (BARC criteria ≥ 3) Composite of non‐haemorrhagic stroke or TIA Individual components of those composites Death and cardiovascular death
Notes	Investigators' conflicts of interest: not reported Funding: Baim Institute for Clinical Research with financial support from Bristol‐Myers Squibb and Pfizer Country: US Setting: 18 study sites in US Comments: none Author's name: Matthew R Reynolds Institution: Lahey Hospital & Medical Center, Burlington, Massachusetts Email: matthew.reynolds@baiminstitute.org Address: Baim Institute for Clinical Research, 930 Commonwealth Avenue, Boston, Massachusetts 02215
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Methods of randomisation not described.
Allocation concealment (selection bias)	Unclear risk	Method of allocation concealment not reported.
Blinding of participants and personnel (performance bias) all outcomes	High risk	Open‐label study.
Blinding of outcome assessment (detection bias) all outcomes	Low risk	Quote: "all potential endpoints were reviewed and adjudicated by an independent endpoints committee. Other procedure‐attributable adverse events not meeting endpoint criteria were reviewed by safety officers of the study sponsor as well as the principal investigators."
Incomplete outcome data (attrition bias) all outcomes	Low risk	Participants flow chart was provided. Attrition was explained and all endpoint analyses were conducted on the evaluable patient population, which included all intention‐to‐treat participants who were randomised.
Selective reporting (reporting bias)	Low risk	Outcomes reported matched published protocol (NCT02608099).