Abstract 12668: Platelet Pharmacogenetics in Common Clinical Practice
Purpose: Antiplatelet drug resistance is a well known problem, causing recurrent cardiovascular events despite adequate guideline therapy. The role of pharmacogenetics has been demonstrated in several large trials reporting polymorphisms related to antiplatelet resistance. However, the influence of these polymorphisms in unselected populations in clinical practice remains to be elucidated. We investigated the best replicated polymorphisms in an unselected population of patients presenting with acute myocardial infarction (AMI).
Methods: Patients with AMI (n=1287) presenting in the Leiden University Medical Center between 2004 and 2010 were treated according to the standardized guideline-based MISSION protocol. All patients underwent a primary PCI. Aspirin and clopidogrel were prescribed to 94% and 98% of the patients respectively. Cardiovascular events (AMI, revascularization or cardiac death) were recorded during the first year after the index event. The selected genetic polymorphisms, COX-1 (-842A>G), P2Y1 (893C>T), GP Ia (807C>T), GP IIIa (PlA1/A2), CYP2C19 (*2, *3 and *17) and ABCB1 (3435T>C), were genotyped using MassArray platform (Sequenom). Associations were tested with a Cox regression model with adjustment for known risk factors.
Results: During follow up, 246 patients (19.1%) suffered from a cardiovascular event. Patients homozygous for the CYP2C19*2 allele had an increased risk of an event, HR 1.91 (95% CI 1.49-2.44), p=3.8x10-7. To a lesser extent, also carriers of the GPIIIa PlA2/A2 genotype were at risk, HR 1.38 (1.02-1.88), p=0.037. The other polymorphisms were not associated with treatment outcome.
Conclusion: We demonstrate that in an unselected all-comers population of AMI patients the CYP2C19*2 allele is associated with an increased risk of cardiovascular events. Testing for this polymorphism might prove useful in identification of patients that could benefit from more potent antiplatelet therapy.
- © 2011 by American Heart Association, Inc.