Summary
Aspirin prevents thrombotic events by inhibiting platelet cyclooxygenase-1 (COX-1),
thus reducing thromboxane A2 formation and platelet aggregation. The C50T polymorphism
of COX-1 is associated with an impaired inhibition of both thromboxane production
and in-vitro platelet aggregation by aspirin. We studied whether this polymorphism
is also associated with the risk of clinical thrombotic events in patients using aspirin.
We included 496 patients admitted to our Coronary Care Unit for various indications
treated with aspirin 80 mg daily. Genotyping for the C50T polymorphism demonstrated
that 86.7% of the patients had the common genotype, and 13.3% had the variant (12.5%
heterozygous, 0.8% homozygous). Baseline variables were well balanced, except that
patients with the common genotype more frequently used aspirin prior to admission
compared to those patients with the variant genotype. The composite primary endpoint
of myocardial infarction, stroke, and/or cardiovascular death occurred in 98 patients
(19.8%). Myocardial infarction occurred in 9.6% of patients, stroke in 1.6%, and cardiovascular
death in 12.1%.The unadjusted hazard ratio (95% CI) for the primary endpoint for patients
with the variant versus the common genotype was 1.07 (0.62–1.85), p=0.8.The adjusted
hazard ratio was 0.86 (0.49–1.50), p=0.6. In prior laboratory studies the COX-1 C50T
polymorphism was associated with an impaired inhibitory effect of aspirin on thromboxane
production and platelet function. However, in this cohort of patients using low-dose
aspirin for secondary prevention the polymorphism was not associated with a higher
risk of atherothrombotic events.
Keywords
Aspirin - antiplatelet therapy - clinical follow-up - cyclooxygenase 1 - pharmacogenetics
