A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease

This study was designed to determine if aspirin resistance is associated with clinical events. Aspirin resistance, defined by platelet function testing and presumed clinical unresponsiveness to aspirin, has been previously reported by our group and others. However, little information exists linking...

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Bibliographic Details
Published in:Journal of the American College of Cardiology 2003-03, Vol.41 (6), p.961-965
Main Authors: Gum, Patricia A, Kottke-Marchant, Kandice, Welsh, Patricia A, White, Jennifer, Topol, Eric J
Format: Article
Language:English
Subjects:
Adult
Aged
Aspirin
Aspirin - therapeutic use
Blood platelets
Blood Platelets - drug effects
Blood Platelets - physiology
Cardiology
Cardiovascular disease
Cardiovascular Diseases - complications
Cardiovascular Diseases - drug therapy
Cardiovascular Diseases - physiopathology
Confidence intervals
Drug Resistance - physiology
Drug therapy
Female
Fibrinolytic Agents - therapeutic use
Follow-Up Studies
Heart attacks
Hemophilia
Humans
Intubation
Kinases
Male
Middle Aged
Mortality
Myocardial Infarction - etiology
Myocardial Infarction - physiopathology
Myocardial Infarction - prevention & control
Outcome Assessment (Health Care)
Plasma
Platelet Function Tests
Prospective Studies
Single-Blind Method
Stroke - etiology
Stroke - physiopathology
Stroke - prevention & control
Studies
Time Factors
Variables
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Summary:This study was designed to determine if aspirin resistance is associated with clinical events. Aspirin resistance, defined by platelet function testing and presumed clinical unresponsiveness to aspirin, has been previously reported by our group and others. However, little information exists linking the laboratory documentation of aspirin resistance and long-term clinical events. We prospectively enrolled 326 stable cardiovascular patients from 1997 to 1999 on aspirin (325 mg/day for ≥7 days) and no other antiplatelet agents. We tested for aspirin sensitivity by optical platelet aggregation using adenosine diphosphate (ADP) and arachidonic acid (AA). The primary outcome was the composite of death, myocardial infarction (MI), or cerebrovascular accident (CVA). Mean follow-up was 679 ± 185 days. Aspirin resistance was defined as a mean aggregation of ≥70% with 10 μM ADP and ≥20% with 0.5 mg/ml AA. Of the patients studied, 17 (5.2%) were aspirin resistant and 309 (94.8%) were not aspirin resistant. During follow-up, aspirin resistance was associated with an increased risk of death, MI, or CVA compared with patients who were aspirin sensitive (24% vs. 10%, hazard ratio [HR] 3.12, 95% confidence interval [CI] 1.10 to 8.90, p = 0.03). Stratified multivariate analyses identified platelet count, age, heart failure, and aspirin resistance to be independently associated with major adverse long-term outcomes (HR for aspirin resistance 4.14, 95% CI 1.42 to 12.06, p = 0.009). This study demonstrates the natural history of aspirin resistance in a stable population, documenting a greater than threefold increase in the risk of major adverse events associated with aspirin resistance.
ISSN:0735-1097
1558-3597
DOI:10.1016/S0735-1097(02)03014-0