Incidence of Stroke in Paroxysmal Versus Sustained Atrial Fibrillation in Patients Taking Oral Anticoagulation or Combined Antiplatelet Therapy: An ACTIVE W Substudy

Stefan H. Hohnloser, MD, FACC; Dimitri Pajitnev, MD; Janice Pogue, PhD; Jeff S. Healey, MD; Marc A. Pfeffer, MD, FACC; Salim Yusuf, MD, FACC; Stuart J. Connolly, MD, FACC


J Am Coll Cardiol. 2007;50(22) 

In This Article

Abstract and Introduction


Objectives: Our goal was to determine the risk of stroke or non-cerebral embolism associated with paroxysmal compared with sustained atrial fibrillation (AF).
Background: The risk of stroke and non-cerebral embolism and the efficacy of oral anticoagulation (OAC) in paroxysmal AF as compared with sustained AF are not precisely known.
Methods: The ACTIVE W (Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events) was a trial comparing OAC to combined antiplatelet therapy with aspirin and clopidogrel for prevention of vascular events in 6,706 AF patients. The incidence of thromboembolic events and major bleeds were compared in patients with paroxysmal AF (n = 1,202) and persistent or permanent AF (n = 5,495).
Results: Patients with paroxysmal AF were younger, had a shorter AF history, more hypertension, and less valvular disease, heart failure, and diabetes mellitus than patients with sustained AF. At baseline, patients with paroxysmal AF had a CHADS2 (cardiac failure, hypertension, age, diabetes, stroke [doubled]) risk score of 1.79 ± 1.03 compared with 2.04 ± 1.12 in patients with sustained AF (p < 0.00001). The annualized risk of stroke or non-central nervous system (CNS) systemic embolism was 2.0 in paroxysmal AF compared with 2.2 in sustained AF (relative risk 0.87, 95% confidence interval [CI] 0.59 to 1.30, p = 0.496). After adjusting for confounding baseline variables, the relative risk was 0.94 (95% CI 0.63 to 1.40, p = 0.755). The incidence of stroke and non-CNS embolism was lower for patients treated with OAC irrespective of type of AF. There were more bleedings of any type in patients receiving clopidogrel plus aspirin, irrespective of the type of AF.
Conclusions: Patients with paroxysmal AF treated with aspirin plus clopidogrel or OAC have a similar risk for thromboembolic events than patients with sustained AF. This risk can be significantly lowered with OAC.


Atrial fibrillation (AF) is associated with increased mortality and morbidity, mainly as a result of thromboembolic complications. Several risk stratification models of different complexity have been introduced to identify AF patients who benefit from oral anticoagulation (OAC).[1] In none of these models, the type of AF—paroxysmal versus persistent or permanent—has emerged as an independent predictor of thromboembolic events. The most recent guidelines on therapy of AF recommend the use of OAC, therefore, for patients with stroke risk factors irrespective of the type of AF.[2] However, this recommendation is based on relatively weak data. In fact, only one retrospective analysis has specifically addressed the risk of stroke in patients with paroxysmal versus chronic AF.[3] This study in 460 patients with paroxysmal AF who were enrolled in the SPAF (Stroke Prevention in Atrial Fibrillation) trials found similar incidences of thromboembolic events for both types of AF. This analysis was based on the SPAF trials conducted more than 15 years ago and was limited to patients treated with aspirin. The definition of "intermittent" AF as used by Hart et al.[3] is different from the definition of paroxysmal AF as used in the current guidelines.[2] More importantly, treatments for AF and for underlying cardiovascular diseases have markedly changed, for instance regarding therapy for arterial hypertension or current international normalized ratio (INR) management. Finally, Hart et al.[3] used only data from patients treated with aspirin and not with OAC. Accordingly, a contemporary study is needed to confirm the stroke risk of patients with paroxysmal as compared with sustained AF. The present study, which is based on data from 6,706 patients, enrolled in the largest AF trial completed (ACTIVE W [Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events]) aims to answer 2 questions: 1) in patients taking OAC or aspirin plus clopidogrel, does paroxysmal AF carry a similar or lower stroke risk compared with persistent or permanent AF? and 2) is there a difference in efficacy and safety of OAC or combined antithrombotic therapy using aspirin plus clopidogrel in patients with paroxysmal AF?


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