The Worry About Clopidogrel "Nonresponsiveness" Identification and Treatment in the Post-Percutaneous Coronary Intervention Patient

Sinai Center for Thrombosis Research, Baltimore, Maryland.
JACC. Cardiovascular Interventions (Impact Factor: 7.35). 11/2009; 2(11):1102-4. DOI: 10.1016/j.jcin.2009.09.005
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Available from: Udaya S Tantry, Jun 20, 2014
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    ABSTRACT: Background: The CYP2C19 genotype is a predictor of adverse cardiovascular events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) treated with clopidogrel. Objective: We aimed to evaluate the cost-effectiveness of a CYP2C19*2 genotype-guided strategy of antiplatelet therapy in ACS patients undergoing PCI, compared to two "no testing" strategies (empiric clopidogrel or prasugrel). Methods: We developed a Markov model to compare three strategies. The model captured adverse cardiovascular events and antiplatelet-related complications. Costs were expressed in 2010 US dollars and estimated using diagnosis-related group codes and Medicare reimbursement rates. The net wholesale price for prasugrel was estimated as $5.45/day. A generic estimate for clopidogrel of $1.00/day was used, and genetic testing was assumed to cost $500. Results: Base case analyses demonstrated little difference between treatment strategies. The genetic testing-guided strategy yielded the most QALYs and was the least costly. Over 15 months, total costs were $18 lower with a gain of 0.004 QALY in the genotype-guided strategy compared to empiric clopidogrel, and $899 lower with a gain of 0.0005 QALY compared to empiric prasugrel. The strongest predictor of the preferred strategy was the relative risk of thrombotic events in carriers compared to wild-type individuals treated with clopidogrel. Above a 47% increased risk, a genotype-guided strategy was the dominant strategy. Above a clopidogrel cost of $3.96 per day, genetic testing was no longer dominant but remained cost-effective. Conclusions: Among ACS patients undergoing PCI, a genotype-guided strategy yields similar outcomes to empiric approaches to treatment, but is marginally less costly and more effective. © 2012 International Society on Thrombosis and Haemostasis.
    Journal of Thrombosis and Haemostasis 11/2012; 11(1). DOI:10.1111/jth.12059 · 5.72 Impact Factor
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    ABSTRACT: Cardiovascular disease is one of the main leading cause of mortality. Approximately, 80% of cardiovascular death occurs in low- and middle-income countries (LMICs). Current guidelines which are based on randomized controlled trials direct the cardiovascular diagnosis and treatment. Yet, such guidelines do not benefit every patient. Recent studies question the ‘one size fits all’ principle particularly in complex traits such as thrombosis. The cost and duration of genetic testing continue to decline rapidly and novel strategies are on the rise to determine individual susceptibility to diseases and responses to therapy. Multidimensional evaluation of the patient with his/her environment, genomics, detailed medical history, and compliance to treatment are crucial in preventing complications from antithrombotic treatment. In this review, we discuss some of the pharmacogenomic features of antithrombotic medications that are currently used. We believe current personalized medicine and pharmacogenomics are pivotal in elucidating contradictory results of randomized controlled trials to test the same antithrombotic regimen on all participants.
    Current Pharmacogenomics and Personalized Medicine (Formerly Current Pharmacogenomics) 03/2015; 12(3). DOI:10.2174/1875692112666141027231225