Antiphospholipid Antibodies and Subsequent Thrombo-occlusive Events in Patients With Ischemic Stroke

• Published in: JAMA : the journal of the American Medical Association 2004-02, Vol.291 (5), p.576-584
• Main Authors: Levine, Steven R, Brey, Robin L, Tilley, Barbara C, Thompson, J L P, Sacco, Ralph L, Sciacca, Robert R, Murphy, A, Lu, Yimeng, Costigan, Teresa M, Rhine, Candi, Levin, Bruce, Triplett, Douglas A, Mohr, J P
• Format: Article
• Language: English
• Subjects: Aged; Antibodies, Antiphospholipid - blood; Anticoagulants - therapeutic use; Aspirin - therapeutic use; Biological and medical sciences; Cohort Studies; Drug therapy; Female; Heart attacks; Humans; Male; Medical sciences; Middle Aged; Neurology; Patients; Platelet Aggregation Inhibitors - therapeutic use; Proportional Hazards Models; Prospective Studies; Randomized Controlled Trials as Topic; Stroke; Stroke - immunology; Stroke - prevention & control; Survival Analysis; Thrombosis - immunology; Thrombosis - prevention & control; Vascular diseases and vascular malformations of the nervous system; Warfarin - therapeutic use
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.291.5.576

CONTEXT The presence of antiphospholipid antibodies (aPL) has been associated with vascular occlusive events. However, the role of aPL in predicting ischemic events, particularly recurrent ischemic stroke, is controversial. OBJECTIVE To evaluate the effect of baseline aPL positivity (ie, positivity for anticardiolipin antibodies [aCL], lupus anticoagulant antibodies [LA], or both) on subsequent thrombo-occlusive events, including recurrent stroke. DESIGN, SETTING, AND PARTICIPANTS The Antiphospholipid Antibodies and Stroke Study (APASS), a prospective cohort study within the Warfarin vs Aspirin Recurrent Stroke Study (WARSS), a randomized double-blind trial (N = 2206) conducted at multiple US clinical sites from June 1993 through June 2000 and comparing adjusted-dose warfarin (target international normalized ratio, 1.4-2.8) and aspirin (325 mg/d) for prevention of recurrent stroke or death. APASS participants were 1770 (80%) WARSS participants who consented to enroll in the APASS, with usable baseline blood samples drawn prior to randomization to the WARSS and analyzed for aPL status within 90 days of index stroke by a central independent laboratory. Quality assurance was performed on approximately 10% of samples by a second independent laboratory. MAIN OUTCOME MEASURE Two-year rate of the composite end point of death from any cause, ischemic stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis, pulmonary embolism, and other systemic thrombo-occlusive events. The primary analysis assessed the outcome associated with aPL positivity within each WARSS treatment group separately, after risk-factor adjustment (since these aPL-positive vs aPL-negative comparisons were not randomized). RESULTS Of the 1770 APASS patients, 720 (41%) were classified as aPL-positive and 1050 (59%) as aPL-negative. There was no increased risk of thrombo-occlusive events associated with baseline aPL status in patients treated with either warfarin (relative risk [RR], 0.99; 95% confidence interval [CI], 0.75-1.31; P = .94), or aspirin (RR, 0.94; 95% CI, 0.70-1.28; P = .71). The overall event rate was 22.2% among aPL-positive and 21.8% among aPL-negative patients. There was no treatment × aPL interaction (P = .91). Patients with baseline positivity for both LA and aCL antibodies tended to have a higher event rate (31.7%) than did patients who tested negative for both antibodies (24.0%) (unadjusted RR, 1.36; 95% CI, 0.97-1.92; P = .07). Classification and regress