This study was designed to determine if aspirin resistance is associated with clinical
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 > or =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 > or =70% with 10 microM
ADP and > or =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.