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Cited by 478Systemic Lupus Erythematosus ResearchAcute Ischemic Stroke ManagementBlood Coagulation and Thrombosis Mechanisms

The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.

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

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APASS Investigators·2004·JAMA
DOI 10.1001/jama.291.5.576
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Abstract

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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Research works printed but not linked: 5

  1. Rand JH, Wu X-X, Andree HAM, et al. Preg- nancy loss in the antiphospholipid-antibody syn- drome-a possible thrombogenic mechanism [pub- lished correction appears in N Engl J Med. 1997;337: 1327]. N Engl J Med. 1997;337:154-160.
  2. Levine JS, Branch DW, Rauch J. The antiphospho- lipid syndrome. N Engl J Med. 2002;346:752-763.
  3. WARSS, APASS, PICSS, and HAS Study Groups. The feasibility of a collaborative double-blind study using an anticoagulant: the Warfarin-Aspirin Recur- rent Stroke Study (WARSS), the Antiphospholipid An- tibodies And Stroke Study (APASS), the Patent fora- men ovale In Cryptogenic Stroke Study (PICSS), and the Hemostatic system Activation Study (HAS). Ce- rebrovasc Dis. 1997;7:100-112.
  4. WARSS Study Group. A double-blind study us- ing an anticoagulant: the design and initial progress of the Warfarin-Aspirin Recurrent Stroke Study (WARSS). Cerebrovasc Dis. 1997;7:100-112.
  5. Turhim S, Rand JH, Goldman M, et al. Antiphos- phatidylserine antibodies are independently associated with ischemic stroke. Neurology. 1999;53:1523-1527.

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Metadata

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
DOI
10.1001/jama.291.5.576
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
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 › Clinical Neurology › 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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