Evaluating the clinical usefulness of platelet function testing: Considerations for the proper application and interpretation of performance measures
ABSTRACT Various diagnostic and prognostic performance measures have been used to describe the clinical usefulness of platelet function testing in the evaluation and management of patients taking P2Y 12 inhibitors, which reduce the risk for thrombosis due to their action on the platelet P2Y 12 receptor. Platelet function tests are used to confirm the presence of an antiplatelet effect of a P2Y 12 inhibitor, and confirmation that the pharmacodynamic effect is associated with a reduction in the rate of thrombosis. Despite this clear association, enthusiasm for the clinical usefulness of platelet function testing has been tempered based on observed sensitivity, specificity, and positive predictive value for the detection of future thrombotic events. However, evaluating the prognostic utility of a test based on diagnostic performance indicators is not appropriate because prognostic tests are not used to diagnose which patients will have events; instead, they are used to assist in risk stratification. Therefore, when evaluating the usefulness of platelet function testing, diagnostic performance measures such as sensitivity, specificity, and predictive values should focus on diagnostic performance in identifying a pharmacodynamic effect, and prognostic performance should be evaluated using prognostic performance measures such as hazard ratios and net reclassification improvement, which are comparable to other well-established risk factors for cardiovascular events.
- Thrombosis and Haemostasis 04/2013; 109(5):789-791. DOI:10.1160/TH13-04-0281 · 5.76 Impact Factor
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ABSTRACT: Pharmacogenomics, the study of the genomics of drug response and adverse effects, holds great promise for more effective individualized (personalized) medicine. Recent evidence supports a role of loss-of-function (LOF) variants in the cytochrome P450 enzyme CYP2C19 as a determinant of clopidogrel response. Patients given clopidogrel after percutaneous coronary intervention who carry LOF variants do not metabolize clopidogrel, a prodrug, into its active form resulting in decreased inhibition of platelet function and a higher likelihood of recurrent cardiovascular events. Despite a large body of evidence supporting clinical utility, adoption of anti-platelet pharmacogenetics into clinical practice has been slow. In this review, we summarize the pharmacokinetic, pharmacodynamic and clinical evidence, identify gaps in knowledge and other barriers that appear to be slowing adoption, and describe CYP2C19 pharmacogenetics implementation projects currently underway. Only when we surmount these barriers will clinicians be able to use pharmacogenetic information in conjunction with the history, physical examination and other medical tests and information to choose the most efficacious anti-platelet therapy for each individual patient.Journal of Human Genetics advance online publication, 23 May 2013; doi:10.1038/jhg.2013.41.Journal of Human Genetics 05/2013; 58(6). DOI:10.1038/jhg.2013.41 · 2.53 Impact Factor
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ABSTRACT: The use of aspirin is considered the "gold standard" for the decrease of major adverse cardiovascular events in patients with atherosclerosis, including peripheral arterial disease (PAD), whereas a dual-antiplatelet regimen with aspirin and clopidogrel is usually indicated for such patients after angioplasty and stent deployment. However, a substantial number of subsequent adverse events still occur, even in patients who receive double-antiplatelet therapy. The "high on-treatment platelet reactivity" (HTPR) phenomenon has been lately recognized and plays a major role in the management of patients with PAD. Greater and more rapid inhibition of platelet aggregation has become the goal for new antiplatelet agents with the expectation of further improving outcomes for percutaneous intervention for PAD. The purpose of this review article is to highlight current evidence regarding the prevalence, aetiology, and clinical implications of HTPR in PAD as well as to discuss the possibilities of novel alternative antiplatelet regiments.CardioVascular and Interventional Radiology 07/2013; 37(3). DOI:10.1007/s00270-013-0707-y · 1.97 Impact Factor