scholarly journals Clinical Pharmacogenetics Implementation Consortium Guidelines for Cytochrome P450-2C19 (CYP2C19) Genotype and Clopidogrel Therapy

2011 ◽  
Vol 90 (2) ◽  
pp. 328-332 ◽  
Author(s):  
S A Scott ◽  
K Sangkuhl ◽  
E E Gardner ◽  
C M Stein ◽  
J-S Hulot ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cyp2c19 Genotype ◽  
Cytochrome P450 2C19 ◽  
Clopidogrel Therapy

Abstract P241: One-Year Cost-Effectiveness of Cytochrome P450 2C19 Genotype-Guided Antiplatelet Therapy in Patients With Acute Coronary Syndromes

2011 ◽  
Vol 4 (suppl_1) ◽  
Author(s):  
Scott L Charland ◽  
Barnabie C Agatep ◽  
Daniel C Malone ◽  
Eric J Stanek
Keyword(s):  
Cytochrome P450 ◽  
Cost Effectiveness ◽  
Antiplatelet Therapy ◽  
Annual Cost ◽  
Extensive Metabolizers ◽  
Cyp2c19 Genotype ◽  
Event Management ◽  
Test Cost ◽  
Cytochrome P450 2C19 ◽  
The Cost

OBJECTIVES: Cytochrome P450 2C19 (CYP2C19) genotype has been shown to affect cardiovascular (CV) outcomes for clopidogrel but not prasugrel. This study evaluates the cost-effectiveness of CYP2C19-guided vs. routine antiplatelet therapy in ACS patients. METHODS: We constructed a literature-based, decision analytic, Markov model (TreeAge 2009) to estimate the cost-effectiveness of CYP2C19-guided aspirin plus either clopidogrel or prasugrel therapy vs. no genotyping. Post-initial ACS CV events were based on the TRITON-TIMI 38 study and related costs were derived primarily using 2007 Healthcare Cost and Utilization Project DRGs for nonfatal MI and stroke, CV death, intracranial hemorrhage, other life-threatening bleed, and minor bleed. Additional costs and disease-state utilities were obtained from other published sources. All costs were adjusted to 2009 $US using the Consumer Price Index medical care component. The model allowed for clopidogrel/prasugrel discontinuation and aspirin monotherapy. Model sensitivity was assessed using 1-way and multi-way analysis of influential parameters. RESULTS: The base case model demonstrated that CYP2C19 genotype guided antiplatelet therapy yielded lower overall annual cost and greater efficacy vs. no genotyping ( Table ). The model was sensitive to (in declining order): clopidogrel cost/day ($1 to $5.78), prasugrel cost/day ($4.09 to $ 6.81), % CYP2C19 extensive metabolizers on clopidogrel (60% to 100%), CYP2C19 test cost ($60 to $250), and monthly CV event management cost. A threshold value for clopidogrel at <$2.14/day favored the no genotyping strategy. However, the genotyping strategy was dominant when clopidogrel cost =$1/day and a CYP2C19 test cost threshold of <$125 on 2-way analysis. CONCLUSIONS: CYP2C19 genotype-guided clopidogrel or prasugrel therapy is cost-effective for up to 1 year in ACS patients, and can remain a preferred strategy at a hypothetical generic clopidogrel cost of $1.00/day. Table Strategy1 Annual Cost Incremental Cost Quality Adjusted Life Year (QALY) Incremental QALY Cost/QALY Incremental Cost Effectiveness (ICER) CYP2C19 Genotype-Guided $ 3,211 0.7212 $ 4,452 No Gentoyping $ 3,331 $120 0.6767 - (0.0445) $ 4,921 (Dominated) 1Base case values:Drug wholesale acquisition cost/day: clopidogrel $4.62, prasugrel $5.45; Baseline post-ACS utility = 0.83; Monthly cost for post-CV event management = $351; CYP2C19 genotyping =$185; After genotyping: 80% of extensive metabolizers, 20% of intermediate metabolizers and 10% of poor metabolizers on clopidogrel; 80% on clopidogrel without genotyping; Willingness to pay = $200

Cytochrome P450 2C19 (CYP2C19) genotype status is not associated with cure rates of dual therapy with rabeprazole and amoxicillin for Helicobacter pylori

2001 ◽  
Vol 120 (5) ◽  
pp. A587 ◽  
Author(s):  
Masakatsu Uchihara ◽  
Namiki Izumi ◽  
Osamu Noguchi ◽  
Yasuhiro Asahina ◽  
Nobuhiko Kanazawa ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Cytochrome P450 ◽  
Dual Therapy ◽  
Cyp2c19 Genotype ◽  
Cytochrome P450 2C19 ◽  
Cure Rates

Abstract TP411: Effects of Triflusal and Clopidogrel in Secondary Prevention of Stroke Based on Cytochrome P450 2C19 Genotyping

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Kyung-Yul Lee ◽  
Sang Won Han ◽  
Yong-Jae Kim ◽  
Seong Hwan Ahn ◽  
Woo-Keun Seo ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Secondary Prevention ◽  
Recurrent Stroke ◽  
Tertiary Care ◽  
Antiplatelet Agents ◽  
Stroke Recurrence ◽  
Cyp2c19 Genotype ◽  
Open Label ◽  
Genotype Group ◽  
Cytochrome P450 2C19

Background: The relationship between stroke recurrence and cytochrome P450 2C19 (CYP2C19) genotype for the secondary prevention of ischemic stroke (IS) is not clearly defined. We investigated the effect of antiplatelet agents based on CYP2C19 genotype in secondary prevention of IS. Methods: In this prospective, multicenter, randomized, parallel-group, open-label, and blind genotype trial, we enrolled first non-cardiogenic IS patients within 30 days prior to screening at the 18 tertiary-care hospitals. Participants received 300 mg triflusal twice a day or 75 mg clopidogrel once daily. CYP2C19 genotyping was done in all patients and genotype results were blind during the study. The primary outcome was the time from randomization to first recurrent IS or hemorrhagic stroke. Efficacy analyses were performed using both the modified intention-to- treat population and the per-protocol population. The study is registered with ClinicalTrials.gov (NCT01174693). Results: This trial failed to meet its recruitment goal due to slow enrollment. A total of 784 (73% of required sample size) patients were followed for a mean of 2.5 years. In poor CYP2C19 genotype group (n=484), 30 (6.2%) patients had a recurrent stroke. The risk of recurrent stroke in triflusal group was 2.9% per year and was not significantly different with clopidogrel group (2.2% per year; hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.6 to 2.53). In clopidogrel treatment group (n=393), 20 (5.1%) had a recurrent stroke. The risk of recurrent stroke in good CYP2C19 genotype was 1.6% per year and was not significantly different with poor genotype (2.2% per year; HR, 0.69; 95% CI, 0.26 to 1.79). Conclusions: In poor CYP2C19 genotype group, either triflusal or clopidogrel was not superior to the other in the prevention of recurrent stroke.

scholarly journals The Pharmacogenetics of Cytochrome P450 2C19 Enzymes - Effects on Clopidogrel and Proton Pump Inhibitors

2014 ◽  
Vol 6 (1) ◽  
pp. 33
Author(s):  
Yusmiati Yusmiati ◽  
Dewi Muliaty
Keyword(s):  
Cytochrome P450 ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Platelet Reactivity ◽  
Active Form ◽  
Anti Platelet Therapy ◽  
Cytochrome P450 2C19 ◽  
Cyp2c19 Gene ◽  
Anti Platelet Drug ◽  
Clopidogrel Therapy

BACKGROUND: Cytochrome P450 (CYP) enzymes play important roles in human, including drug metabolism. CYP2 is the largest family of human CYP, with its sequence comprising almost one third of all CYP sequences, and responsible for the metabolism of approximately 2% of clinically administrated drugs. One of the most important enzymes in this family is the CYP2C19 enzyme. The CYP2C19 gene is polymorphic, and the variation is common especially in the Asian population.CONTENT: CYP2C19 is responsible for the metabolism of various drugs, including proton pump inhibitors (PPIs) such as omeprazole and lansoprazole, psychotropic drugs including diazepam and imipramine, anticonvulsants such as phenobarbital and mephenytoin. and the recently most studied the anti-platelet drug, clopidogrel, and many others. Drugs metabolized predominantly by this enzyme like clopidogrel and PPIs might be much affected by the genotype status of CYP2C19. Clopidogrel is a pro-drug requiring a group of enzymes to convert to its active form, particularly the CYP2C19. PPIs are metabolized to its inactive metabolites mainly by CYP2C19 in the liver. Some PPIs are inhibitor of CYP2C19 enzymes, and interaction of PPIs and clopidogrel has been widely studied.SUMMARY: The association of CYP2C19 genotypes with the plasma level of active clopidogrel and platelet reactivity in individual taking this drug is well-established. Although conflicting results still exist for the association of CYP2C19 genotypes to the clinical outcomes of clopidogrel therapy, this effect seems to be consistent in patients receiving clopidogrel for coronary stents. Due to the interaction of certain PPIs and clopidogrel, the use of PPIs other than omeprazole is recommended, especially for patients taking dual anti platelet therapy of clopidogrel and aspirin.KEYWORDS: pharmacogenetics, CYP2C19, proton pump inhibitors, clopidogrel

scholarly journals Effects of Cytochrome P450 2C19 and Paraoxonase 1 Polymorphisms on Antiplatelet Response to Clopidogrel Therapy in Patients with Coronary Artery Disease

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e110188 ◽  
Author(s):  
Damrus Tresukosol ◽  
Bhoom Suktitipat ◽  
Saowalak Hunnangkul ◽  
Ruttakarn Kamkaew ◽  
Saiphon Poldee ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Cytochrome P450 ◽  
Coronary Artery ◽  
Paraoxonase 1 ◽  
Cytochrome P450 2C19 ◽  
Clopidogrel Therapy ◽  
Artery Disease
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