[Antiplatelet therapy in coronary heart disease. Some problems and achivements]

Abstract

Standard double antiplatelet therapy (aspirin plus clopidogrel) used in patients with coronary artery disease during acute coronary syndromes (ACS) and/or in conjunction with percutaneous coronary interventions (PCI) has some limitations. Relatively large proportion of patients has "laboratory" resistance to clopidogrel - an essential component of standard therapy. Basic weakness of this agent is necessity to be converted into active metabolite by CYP 450 enzymes. Other drugs potentially interfere with this conversion. The puzzle of clinical value of obvious laboratory interaction of clopidogrel with its conjecturally almost obligatory companions proton pump inhibitors is still unresolved. It has been shown recently that loss of function alleles of some CYP450 genes especially CYP2C19*2 are responsible for reduced reaction of platelets to clopidogrel. Detection of this allele is possible. However practical application of such genetic testing is subject of disagreement among experts. Another way for therapy guidance is use of platelet function testing. But at present there is no agreement concerning preferable test. Studies aimed at clarification of practical role of some laboratory test are close to completion. Recognition of resistance by any method calls forth administration of higher doses of clopidogrel or use of novel agents. CURRENT trial has recently demonstrated advantages of clopidogrel double dose in ACS patients subjected to PCI. Novel P2Y12 receptor inhibitors prasugrel and ticagrelor have been shown to be superior to clopidogrel in large randomized trials. Direct P2Y12 antagonist ticagrelor seems to be especially attractive because of effect on total mortality and acceptable rate of bleeding. Among agents under study thrombin receptor blockers appear most promising.