Value of platelet pharmacogenetics in common clinical practice of patients with ST-segment elevation myocardial infarction

• Published in: International journal of cardiology Vol. 167; no. 6; pp. 2882 - 2888
• Main Authors: Verschuren, Jeffrey J.W, Boden, Helèn, Wessels, Judith A.M, van der Hoeven, Bas L, Trompet, Stella, Heijmans, Bastiaan T, Putter, Hein, Guchelaar, Henk-Jan, Schalij, Martin J, Jukema, J. Wouter
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 10.09.2013; Elsevier
• Subjects: Aged; Aged, 80 and over; Antiplatelet therapy; Aryl Hydrocarbon Hydroxylases - genetics; Biological and medical sciences; Blood Platelets - drug effects; Blood Platelets - physiology; Cardiology. Vascular system; Cardiovascular; Cohort Studies; Coronary heart disease; Coronary Thrombosis - blood; Coronary Thrombosis - drug therapy; Coronary Thrombosis - genetics; Cyclooxygenase 1; Cyclooxygenase 1 - genetics; Cytochrome P-450 CYP2C19; Cytochrome P450 2C19; Female; Follow-Up Studies; Heart; Humans; Male; Medical sciences; Middle Aged; Myocardial Infarction - blood; Myocardial Infarction - drug therapy; Myocardial Infarction - genetics; Myocarditis. Cardiomyopathies; Pharmacogenetics; Pharmacogenetics - methods; Platelet Aggregation - drug effects; Platelet Aggregation - physiology; Platelet Aggregation Inhibitors - pharmacology; Platelet Aggregation Inhibitors - therapeutic use; Polymorphism, Single Nucleotide - genetics; Population Surveillance - methods; ST-segment elevation myocardial infarction; Stents - adverse effects; Ticlopidine - analogs & derivatives; Ticlopidine - pharmacology; Ticlopidine - therapeutic use; Treatment outcome; Antiplatelet therapy; Treatment outcome; Pharmacogenetics; ST-segment elevation myocardial infarction; Cytochrome P450 2C19; Cyclooxygenase 1; Myocardial infarction; Prognosis; Cardiovascular disease; Myocardial disease; ST elevation; Genetics; Evolution; Cardiology; Human; Enzyme; Cytochrome P450; Patient; Coronary heart disease; Antiplatelet agent; Chemotherapy; Platelet; Treatment; Professional practice; Oxidoreductases
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2012.07.020

Abstract Background Antiplatelet drug resistance is a well-known problem, causing recurrent cardiovascular events. Multiple genetic polymorphisms have been related to antiplatelet resistance by several large trials, however data from common clinical practice is limited. We examined the influence of previously described polymorphisms, related to aspirin and clopidogrel resistance, on treatment outcome in a real life unselected population of patients presenting with ST-segment elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention. Methods and results This cohort study consisted of 1327 patients with STEMI. Patients were treated according to a standardized guideline-based protocol. Nine polymorphisms, COX1 (− 842A > G), P2Y1 (893C > T), GPIa (807C > T), GPIIIa (PlA1/A2), CYP2C19 (*2, *3 and *17), ABCB1 (3435T > C) and PON1 (576A > G), were genotyped. During 1 year of follow up the primary endpoint, a composite of cardiac death or recurrent myocardial infarction, was reached in 86 patients. The COX1 and CYP2C19*2 polymorphisms were associated with the primary endpoint, HR 2.55 (95% CI 1.48–4.40), P = 0.001 and HR 2.03 (1.34–3.09) P = 0.001, respectively. The combined analysis demonstrated a 2.5-fold increased risk for individuals with ≥ 2 risk alleles, P = 6.9 × 10–9 . The association of COX1 was driven by mortality related events whereas that of CYP2C19*2 was mainly attributed to myocardial infarction and stent thrombosis. Conclusion In this unselected, real life population of STEMI patient on dual-antiplatelet therapy, the polymorphisms COX1 –842A > G and CYP2C19*2 were determinants of thrombotic complications during follow-up. We show that in a clinical setting, testing for these polymorphisms could be of value in the identification of STEMI patients at risk for recurrent cardiovascular events.