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. OBJECTIVES: We aimed to evaluate the cost-effectiveness of a CYP2C19*2 genotype-guided strategy of antiplatelet therapy in ACS patients undergoing PCI, compared with 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 per day. A generic estimate for clopidogrel of $1.00 per 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 with empiric clopidogrel, and $899 lower with a gain of 0.0005 QALY compared with empiric prasugrel. The strongest predictor of the preferred strategy was the relative risk of thrombotic events in carriers compared with 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.
Subject(s)
Acute Coronary Syndrome/economics , Acute Coronary Syndrome/therapy , Aryl Hydrocarbon Hydroxylases/genetics , Genetic Testing/economics , Health Care Costs , Percutaneous Coronary Intervention/economics , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/genetics , Acute Coronary Syndrome/mortality , Aryl Hydrocarbon Hydroxylases/metabolism , Cerebrovascular Disorders/etiology , Clopidogrel , Computer Simulation , Cost-Benefit Analysis , Cytochrome P-450 CYP2C19 , Decision Support Techniques , Disease-Free Survival , Drug Costs , Gene Frequency , Genetic Predisposition to Disease , Hemorrhage/etiology , Humans , Insurance, Health, Reimbursement/economics , Kaplan-Meier Estimate , Markov Chains , Medicare/economics , Models, Economic , Myocardial Infarction/etiology , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/mortality , Pharmacogenetics/economics , Phenotype , Piperazines/economics , Piperazines/metabolism , Piperazines/therapeutic use , Platelet Aggregation Inhibitors/economics , Platelet Aggregation Inhibitors/metabolism , Platelet Aggregation Inhibitors/therapeutic use , Prasugrel Hydrochloride , Predictive Value of Tests , Quality-Adjusted Life Years , Risk Assessment , Risk Factors , Thiophenes/economics , Thiophenes/metabolism , Thiophenes/therapeutic use , Thrombosis/economics , Thrombosis/genetics , Thrombosis/prevention & control , Ticlopidine/analogs & derivatives , Ticlopidine/economics , Ticlopidine/metabolism , Ticlopidine/therapeutic use , Time Factors , Treatment Outcome , United StatesABSTRACT
Bacteria isolates belonging to the genera Bacillus, Corynebacterium, Aeromonas, and Enterobacter were isolated from a municipal waste landfill in Durham, NC. Bacterial counts obtained with three general purpose media were log(10) colony-forming units (cfu)/g of 9.30, 9. 26, and 9.20 respectively for Plate Count Agar, Brain Heart Infusion Agar, and Nutrient Agar. Coliform count from MacConkey agar was log(10) 7.28/g sample. Isolates were generally sensitive to tetracycline and chloramphenicol (13 of 14 isolates) and generally resistant to ampicillin (9 of 9), erythromycin (10 of 14), streptomycin (8 of 14), with 3 of 14 isolates having multiple resistance to the last three antibiotics. A dose-independent growth response to ampicillin was observed for two isolates. The detection of a 22,000-bp plasmid in one but not in the second ampicillin-resistant isolate suggests more than one mechanism of antibiotic resistance.
