Higher Risk of Death and Stroke in Patients With Persistent vs. Paroxysmal Atrial Fibrillation

Results From the Rocket-AF Trial

Benjamin A. Steinberg; Anne S. Hellkamp; Yuliya Lokhnygina; Manesh R. Patel; Günter Breithardt; Graeme J. Hankey; Richard C. Becker; Daniel E. Singer; Jonathan L. Halperin; Werner Hacke; Christopher C. Nessel; Scott D. Berkowitz; Kenneth W. Mahaffey; Keith A.A. Fox; Robert M. Califf; Jonathan P. Piccini


Eur Heart J. 2015;36(5):288-296. 

In This Article

Abstract and Introduction


Aim Anticoagulation prophylaxis for stroke is recommended for at-risk patients with either persistent or paroxysmal atrial fibrillation (AF). We compared outcomes in patients with persistent vs. paroxysmal AF receiving oral anticoagulation.

Methods and results Patients randomized in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial (n = 14 264) were grouped by baseline AF category: paroxysmal or persistent. Multivariable adjustment was performed to compare thrombo-embolic events, bleeding, and death between groups, in high-risk subgroups, and across treatment assignment (rivaroxaban or warfarin). Of 14 062 patients, 11 548 (82%) had persistent AF and 2514 (18%) had paroxysmal AF. Patients with persistent AF were marginally older (73 vs. 72, P = 0.03), less likely female (39 vs. 45%, P < 0.0001), and more likely to have previously used vitamin K antagonists (64 vs. 56%, P < 0.0001) compared with patients with paroxysmal AF. In patients randomized to warfarin, time in therapeutic range was similar (58 vs. 57%, P = 0.94). Patients with persistent AF had higher adjusted rates of stroke or systemic embolism (2.18 vs. 1.73 events per 100-patient-years, P = 0.048) and all-cause mortality (4.78 vs. 3.52, P = 0.006). Rates of major bleeding were similar (3.55 vs. 3.31, P = 0.77). Rates of stroke or systemic embolism in both types of AF did not differ by treatment assignment (rivaroxaban vs. warfarin, P interaction = 0.6).

Conclusion In patients with AF at moderate-to-high risk of stroke receiving anticoagulation, those with persistent AF have a higher risk of thrombo-embolic events and worse survival compared with paroxysmal AF.


Atrial fibrillation (AF) is a progressive disorder, often transitioning from intermittent to continuous arrhythmia. Patients experiencing episodic AF, self-terminating within 7 days, are said to have paroxysmal AF; patients whose arrhythmia persists beyond 7 days (or requires intervention to terminate) are considered to have persistent AF. Several prior studies have documented symptomatic, physiologic, and anatomic differences between patients with paroxysmal and persistent AF.[1,2] This categorization of AF can also have important implications for approaches to maintain sinus rhythm.[3] All the patients with AF are at an increased risk of thrombo-embolism (stroke or systemic embolism) compared with patients without AF, and anticoagulation therapies are recommended in all patients with AF who are at moderate-to-high risk of stroke.[4,5] The distinction between paroxysmal and persistent AF has not been used to guide choice of stroke prophylaxis, as it remains unclear whether patients with persistent AF are at higher risk compared with those with paroxysmal AF, particularly in patients with additional risk factors for stroke.[6] The objectives of the current analysis were to (i) measure the differences, if any, in outcomes between anticoagulated patients with persistent vs. paroxysmal AF who had additional risk factors for stroke, and (ii) determine whether there was a difference in treatment effect between rivaroxaban and warfarin in these groups.