Influence of genetic variants and drug interactions on the response to antiplatelet drugs

Antiplatelet therapy plays an important role in the treatment of cardiovascular disease. The combination of acetylsalicylic acid and clopidogrel is routine care in patients with acute coronary syndromes (ACS) or undergoing percutaneous coronary interventions (PCI). Although the effectiveness of antiplatelet therapy is well established, studies have shown interindividual variability in the response to both antiplatelet drugs. This variability in response results in complications at both ends of the therapeutic spectrum (bleeding or thrombosis). Common genetic variations and co-prescribed drugs modify the effectiveness of clopidogrel and acetylsalicylic acid. TH In this thesis, several common genetic variants in enzymes involved in the pharmacokinetics and –dynamics of clopidogrel and acetylsalicylic acid were found to modify the effectiveness of both drugs. Furthermore, the concomitant use of certain proton pump inhibitors, calcium channel blockers and sulfonylureas was associated with an impaired response to clopidogrel.