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CLINICAL RESEARCH: HEART RHYTHM DISORDER

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 for the ACTIVE W Investigators

^_* Department of Cardiology, Division of Electrophysiology, J. W. Goethe University, Frankfurt, Germany
Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Brigham and Women’s Hospital, Boston, Massachusetts.

Manuscript received May 24, 2007; revised manuscript received July 10, 2007, accepted July 24, 2007.

^_* Reprint requests and correspondence: Dr. Stefan H. Hohnloser, J. W. Goethe University, Department of Cardiology, Division of Electrophysiology, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. (Email: Hohnloser{at}em.uni-frankfurt.de).

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. (The ACTIVE W trial; http://www.clinicaltrials.gov/ct/show/NCT00243178 [ClinicalTrials.gov] ; NCT00243178)

Abbreviations and Acronyms   AF = atrial fibrillation   CI = confidence interval   CNS = central nervous system   INR = international normalized ratio   OAC = oral anticoagulation   RR = relative risk

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