Abstract
Antiplatelet drugs are recommended for secondary prevention of recurrent cardiovascular events in patients who experience diseases in which the pathophysiology is associated with platelet aggregation and atherosclerosis, including acute coronary syndrome, transient ischemic attack, ischemic stroke, and peripheral artery disease. In the current thesis, we aimed to evaluate the time
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trends of prescriptions of antiplatelet drugs after a myocardial infarction, ischemic stroke, and transient ischemic attack; and to assess the effectiveness and safety (bleeding risk) of antiplatelet drugs as secondary prevention for cardiovascular diseases in daily practice, taking into account genetic and non-genetic factors either as confounders or effect modifiers. In our drug utilization studies, we found that secondary prevention with antiplatelet drugs after the occurrence of a cardiovascular event, particularly myocardial infarction, ischemic stroke, or transient ischemic attack, is still not optimal, with no start at all or early discontinuation of antiplatelet drugs. Some patients restarted the use of antiplatelet drugs after discontinuation. A comparative effectiveness and safety study on antiplatelet regimens after a first ischemic stroke or transient ischemic attack in daily practice suggested that the recommended aspirin-dipyridamole regimen based on experimental studies also has a favourable benefit-risk profile compared to the other antiplatelet regimens in real-life circumstances. In another study, the association between the use of antiplatelet drugs and out-of-hospital sudden cardiac arrest with confirmed ventricular tachycardia/ventricular fibrillation in patients with coronary artery disease was evaluated. The use of aspirin monotherapy was proven to be significantly associated with a lower risk of out-of-hospital sudden cardiac arrest compared to no use of antiplatelet drugs. Furthermore, in several studies we assessed the role of genetic factors in the effectiveness of antiplatelet drugs as secondary prevention of cardiovascular diseases. A review on studies assessing the pharmacogenetics of oral antiplatelet drugs in the treatment of coronary artery disease showed that only the CYP2C19 loss-of-function alleles were consistently associated with a decreased effect of clopidogrel on the prevention of cardiovascular events. However, this polymorphism explains only 12% of the variability of the response of clopidogrel. In a pharmacogenetic study we found that genetic variants in the PPAR-α gene (G209A and A208G) were associated with lower platelet reactivity in patients with non-urgent percutaneous coronary intervention and stenting co-treated with clopidogrel and statins/fibrates (lipid-lowering drugs). Lastly, we discussed the application of routine electronic health record databases for pharmacogenetic research. We suggested three models of data collection in using electronic health record databases for pharmacogenetic research. In conclusion, we have found that secondary prevention with antiplatelet drugs after the occurrence of a cardiovascular event, particularly myocardial infarction, ischemic stroke, or transient ischemic attack, is still not optimal. Furthermore, several genetic and non-genetic factors influence the effectiveness and safety of antiplatelet drugs after a cardiovascular event.
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