Published Online
on January 25, 2007

A more recent version of this article appeared on March 1, 2007

This Article Full Text (PDF) CME: Take the course for this article: Stroke: March 2007, Volume 38, Number 3 All Versions of this Article: 38/3/874    most recent 01.STR.0000258004.64840.0bv1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Akins, P. T. Articles by Albers, G. W. Search for Related Content PubMed PubMed Citation Articles by Akins, P. T. Articles by Albers, G. W. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ACETYLSALICYLIC ACID WARFARIN Medline Plus Health Information Atrial Fibrillation Blood Thinners Stroke Related Collections Secondary prevention Coumarins Other anticoagulants Embolic stroke Anticoagulants

Submitted on May 23, 2006
Revised on September 28, 2006
Accepted on October 3, 2006

Secondary Stroke Prevention With Ximelagatran Versus Warfarin in Patients With Atrial Fibrillation. Pooled Analysis of SPORTIF III and V Clinical Trials

Paul T. Akins MD, PhD^*; Harvey A. Feldman MD; Robert G. Zoble MD, PhD; David Newman MD; Stefan G. Spitzer MD; Hans-Christoph Diener MD; and Gregory W. Albers MD

From the Mercy Stroke Center (P.T.A.), Sacramento, Calif; Nova Southeastern University (H.A.F.), Ft. Lauderdale, Fla; James A. Haley Veterans Administration Medical Center (R.G.Z.), Tampa, Fla; University of Toronto (D.N.), Toronto, Canada; Praxisklinik Herz und Gefässe (S.G.S.), Dresden, Germany; University of Duisburg-Essen (H.-C.D.), Essen, Germany; and the Stanford Stroke Center (G.W.A.), Palo Alto, Calif.

^* To whom correspondence should be addressed. E-mail: akins{at}surewest.net.

Background and Purpose--Patients with nonvalvular atrial fibrillation and prior stroke or transient ischemic attack (TIA) are at high risk for recurrent stroke. We investigated whether ximelagatran was noninferior to warfarin in patients with prior stroke or TIA.

Methods--We analyzed pooled data from the SPORTIF III and V trials in patients with prior stroke/TIA. The primary outcome was the composite annual rate of both ischemic and hemorrhagic strokes and systemic embolic events. Secondary analyses considered ischemic and hemorrhagic strokes separately, bleeding, and nonrandomized, concomitant therapy with aspirin 100 mg/d.

Results--Patients from SPORTIF III (n=3407) and SPORTIF V (n=3922) trials were categorized by prior stroke/TIA (21%) versus no prior stroke/TIA (79%) and by treatment group (ximelagatran vs warfarin). The primary event rate in patients with prior stroke/TIA was 2.83%/y with ximelagatran and 3.27%/y with warfarin (absolute difference, -0.44%; 95% CI, -1.88 to1.01; P=0.625). In those without prior stroke/TIA, the primary event rate was 1.31%/y with ximelagatran and 1.26%/y with warfarin (P=NS). Ischemic strokes outnumbered cerebral hemorrhages with both warfarin (31 of 36) and ximelagatran (30 of 32) treatment (difference between treatments was not significant). Combining aspirin with either anticoagulant was associated with higher rates of major bleeding (1.5%/y with warfarin and 4.95%/y with warfarin plus aspirin, P=0.004; 2.35%/y with ximelagatran and 5.09%/y with ximelagatran plus aspirin, P=0.046) but not lower rates of primary events.

Conclusions--Ximelagatran was at least as effective as well-controlled warfarin for the secondary prevention of stroke. The nonrandomized, concomitant treatment with aspirin and anticoagulation was associated with increased bleeding without evidence of a reduction in primary outcome events.

Key words: atrial fibrillation • aspirin • direct thrombin inhibitor • stroke prevention • warfarin

This article has been cited by other articles:

				P. Kirchhof, J. Bax, C. Blomstrom-Lundquist, H. Calkins, A. J. Camm, R. Cappato, F. Cosio, H. Crijns, H.-C. Diener, A. Goette, et al. Early and comprehensive management of atrial fibrillation: Proceedings from the 2nd AFNET/EHRA consensus conference on atrial fibrillation entitled 'research perspectives in atrial fibrillation' Europace, July 1, 2009; 11(7): 860 - 885. [Full Text] [PDF]

				N U Weir An update on cardioembolic stroke Postgrad. Med. J., March 1, 2008; 84(989): 133 - 142. [Abstract] [Full Text] [PDF]

				P. Kirchhof, A. Auricchio, J. Bax, H. Crijns, J. Camm, H.-C. Diener, A. Goette, G. Hindricks, S. Hohnloser, L. Kappenberger, et al. Outcome parameters for trials in atrial fibrillation: Recommendations from a consensus conference organized by the German Atrial Fibrillation Competence NETwork and the European Heart Rhythm Association Europace, November 1, 2007; 9(11): 1006 - 1023. [Abstract] [Full Text] [PDF]

				D. A. Pearson Bone Health and Osteoporosis: The Role of Vitamin K and Potential Antagonism by Anticoagulants Nutr Clin Pract, October 1, 2007; 22(5): 517 - 544. [Abstract] [Full Text] [PDF]

				L. Testa, W. Van Gaal, P. Agostoni, A. Abbate, G. Trotta, and G. G.L. Biondi-Zoccai Ximelagatran Versus Warfarin in the Prevention of Atrial Fibrillation-Related Stroke: Both Sides of the Story Stroke, July 1, 2007; 38(7): e57 - e57. [Full Text] [PDF]