Antiphospholipid Antibodies and subsequent thrombo-occlusive events in patients with ischemic stroke
Open accessAbstract
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 x 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 warranted.
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No current evidence shows oral anticoagulants are superior to antiplatelet therapy.
“As there is currently no evidence to support the superiority of oral anticoagulant therapy over antiplatelet therapy [15], antiplatelet drugs are generally recommended after an episode of stroke.”
From Clinical course of high‐risk patients diagnosed with antiphospholipid syndrome (2010) · cites this paper as [15]
The COMMENT section reports that warfarin was not associated with fewer thrombo-occlusive events than aspirin in the studied stroke cohort. That supports the comparison, but the citing sentence generalizes it to all oral anticoagulants and antiplatelet therapies; the paper does not establish that broader claim. No page number is available in the supplied copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredAn early study in older patients with strokes reported no difference in event recurrences between low-dose aspirin and warfarin, but antiphospholipid antibody was tested only once and was mainly of low titre.
“An early study in older patients with strokes reported no difference in event recurrences between LDA and warfarin, but aPL was tested only once and was mainly of low titre in this study.33”
From EULAR recommendations for the management of antiphospholipid syndrome in adults (2019) · cites this paper as [33]
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- Authors
- APASS Investigators
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- APASS Investigators
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2004-02-04
- Volume
- 291
- Issue
- 5
- Pages
- 576
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W2110502968
- Cited by
- 478
- References
- 41
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 10 · 2023: 7 · 2022: 8 · 2021: 15 · 2020: 17 · 2019: 21 · 2018: 11 · 2017: 20 · 2016: 19 · 2015: 21 · 2014: 23 · 2013: 15 · 2012: 27
- FWCI
- 23.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (1K24NS43992, K24NS043992, 1R01 NS 30896, R01NS030896, 1R01 NS 28371, R01NS028371)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- antiphospholipid antibodies, anticardiolipin antibodies, lupus anticoagulant, recurrent ischemic stroke, warfarin, aspirin, stroke prevention, transient ischemic attack, myocardial infarction, deep vein thrombosis, pulmonary embolism, risk prediction
- MeSH terms
- Aged, Anticoagulants, Aspirin, Female, Humans, Male, Middle Aged, Platelet Aggregation Inhibitors, Prospective Studies, Thrombosis, Warfarin, Cohort Studies, Proportional Hazards Models, Survival Analysis, Randomized Controlled Trials as Topic, Antibodies, Antiphospholipid, Stroke
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