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
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 regression tree analyses did not identify a specific LA test or aCL isotype
or titer that was associated with increased risk of thrombo-occlusive event.
Conclusions The presence of aPL (either LA or aCL) among patients with ischemic
stroke does not predict either increased risk for subsequent vascular occlusive
events over 2 years or a differential response to aspirin or warfarin therapy.
Routine screening for aPL in patients with ischemic stroke does not appear