TY - JOUR
T1 - The C50T polymorphism of the cyclooxygenase-I gene and the risk of thrombotic events during low-dose therapy with acetyl salicylic acid
AU - Clappers, Nick
AU - van Oijen, Martijn G. H.
AU - Sundaresan, Santosh
AU - Brouwer, Marc A.
AU - te Morsche, Rene H. M.
AU - Keuper, Wessel
AU - Peters, Wilbert H. M.
AU - Drenth, Joost P. H.
AU - Verheugt, Freek W. A.
PY - 2008
Y1 - 2008
N2 - prevents thrombotic events by inhibiting platelet cyclooxygenase-I (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-I 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
AB - prevents thrombotic events by inhibiting platelet cyclooxygenase-I (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-I 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
U2 - https://doi.org/10.1160/THOB-03-0172
DO - https://doi.org/10.1160/THOB-03-0172
M3 - Article
C2 - 18612540
SN - 0340-6245
VL - 100
SP - 70
EP - 75
JO - Thrombosis and haemostasis
JF - Thrombosis and haemostasis
IS - 1
ER -