Meaningful Use of Pharmacogenetics

Ratain, Mark J.

doi:10.1038/clpt.2014.188

Cited by 18 publications

(19 citation statements)

References 10 publications

(16 reference statements)

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“…Domain 4 was the likelihood of recommending pharmacogenetic testing when patient genotypes were not already available (questions #6-8), barring commonly perceived barriers (e.g., availability, affordability, and timeliness [5][6][7][8][9][10][11][12][13][14][15]). The rationale for future science group Physicians' attitudes toward pharmacogenetics Short Communication domain 1 is based on the current debate over the levels of evidence required for the clinical implementation of pharmacogenetics [24][25][26][27]. The rationale for domain 2 is based on the decision to weigh the risk/benefit profile prior to pharmacogenetic testing, which physicians must weigh prior to any type of clinical testing.…”

Section: Surveymentioning

confidence: 99%

Physicians’ Attitudes Toward Pharmacogenetic Testing Before and After Pharmacogenetic Education

Luzum

2016

Per. Med.

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Aim:Our aim was to evaluate physicians' attitudes toward pharmacogenetic testing before and after pharmacogenetic education. Methods: In total, 12 physicians (∼40% response rate) completed a survey with eight questions on 10-point scales on their attitudes toward pharmacogenetic testing before and after a 1-h grand rounds presentation on pharmacogenetics. Differences in question scores overall, among training levels (resident/fellow/attending), and specific drugs (clopidogrel/simvastatin/warfarin) were assessed using Wilcoxon signed-rank and exact Kruskal-Wallis tests. Results & conclusion: The scores for all eight questions increased, with statistically significant (p < 0.05) increases for four out of eight questions. The scores were similar among training levels, but the postscores for clopidogrel were significantly higher than for simvastatin and warfarin. In conclusion, brief pharmacogenetic education can significantly affect physicians' attitudes toward pharmacogenetic testing.

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Section: Surveymentioning

confidence: 99%

Physicians’ Attitudes Toward Pharmacogenetic Testing Before and After Pharmacogenetic Education

Luzum

2016

Per. Med.

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“…An alternative approach could be a prospective nonrandomized study where genetic testing is incorporated into clinical care and compared with standard dosing practices in a more realistic setting to better determine the utility of genetic testing. [60][61][62] Two ongoing RCTs [WARFARIN Study (NCT01305148) and GIFT (NCT01006733)] are using incidence of adverse events, including bleeding and thromboembolism, as the primary study outcomes. This is in contrast to COAG and EU-PACT, which used time in therapeutic range as a primary outcome.…”

Section: Future Directionsmentioning

confidence: 99%

Clinical Practice Recommendations on Genetic Testing of CYP2C9 and VKORC1 Variants in Warfarin Therapy

Shaw

Amstutz

Kim

et al. 2015

Therapeutic Drug Monitoring

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Objective: To systematically review evidence on genetic variants influencing outcomes during warfarin therapy and provide practice recommendations addressing the key questions: (1) Should genetic testing be performed in patients with an indication for warfarin therapy to improve achievement of stable anticoagulation and reduce adverse effects? (2) Are there subgroups of patients who may benefit more from genetic testing compared with others? (3) How should patients with an indication for warfarin therapy be managed based on their genetic test results?Methods: A systematic literature search was performed for VKORC1 and CYP2C9 and their association with warfarin therapy. Evidence was critically appraised, and clinical practice recommendations were developed based on expert group consensus.Results: Testing of VKORC1 (21639G.A), CYP2C9*2, and CYP2C9*3 should be considered for all patients, including pediatric patients, within the first 2 weeks of therapy or after a bleeding event. Testing for CYP2C9*5, *6, *8, or *11 and CYP4F2 (V433M) is currently not recommended. Testing should also be considered for all patients who are at increased risk of bleeding complications, who consistently show out-of-range international normalized ratios, or suffer adverse events while receiving warfarin. Genotyping results should be interpreted using a pharmacogenetic dosing algorithm to estimate the required dose.Significance: This review provides the latest update on genetic markers for warfarin therapy, clinical practice recommendations as a basis for informed decision making regarding the use of genotypeguided dosing in patients with an indication for warfarin therapy, and identifies knowledge gaps to guide future research.

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“…While acknowledging the small sample size and retrospective design, results from this study were consistent with the known role of CYP2D6 in the metabolism of metoprolol and the activation of carvedilol. Although many argue whether prospective, randomized clinical trial validation for every new personalized dosing strategy, especially for drugs already on the market, is feasible or warranted (48–50), results from this study suggest CYP2D6 may have predictive value regarding tolerable maintenance doses of metoprolol or carvedilol.…”

Section: Discussionmentioning

confidence: 88%

CYP2D6 Genetic Variation and Beta-Blocker Maintenance Dose in Patients with Heart Failure

Luzum

Sweet

Binkley³

et al. 2017

Pharm Res

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Purpose This study examined whether a CYP2D6 polymorphism (CYP2D6*4) was related to beta-blocker maintenance dose in patients with heart failure. Methods Logistic regression modeling was utilized in a retrospective chart-review analysis of heart-failure patients (60% Male, 90% of European descent) to assess whether CYP2D6*4 (non-functional CYP2D6 allele present in 1 of 5 individuals of European descent) is associated with maintenance dose of carvedilol (n=65) or metoprolol (n=33). Results CYP2D6*4 was associated with lower maintenance dose of metoprolol (OR 0.13 [95% CI 0.02–0.75] p=0.023), and a trend was observed between CYP2D6*4 and higher maintenance dose of carvedilol (OR 2.94 [95% CI 0.84–10.30] p=0.093). None of the patients that carried CYP2D6*4 achieved the recommended target dose of metoprolol (50mg/day). Conclusion Consistent with the role of CYP2D6 in the metabolism of metoprolol, the tolerated maintenance dose of metoprolol was lower in CYP2D6*4 carriers compared to non-carriers. Consistent with the role of CYP2D6 in activation of carvedilol, tolerated maintenance dose of carvedilol was higher in CYP2D6*4 carriers compared to non-carriers. Further investigation is warranted to ascertain the potential of CYP2D6 as a potential predictive biomarker of beta-blocker maintenance dose in heart failure patients.

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Meaningful Use of Pharmacogenetics

Cited by 18 publications

References 10 publications

Physicians’ Attitudes Toward Pharmacogenetic Testing Before and After Pharmacogenetic Education

Physicians’ Attitudes Toward Pharmacogenetic Testing Before and After Pharmacogenetic Education

Clinical Practice Recommendations on Genetic Testing of CYP2C9 and VKORC1 Variants in Warfarin Therapy

CYP2D6 Genetic Variation and Beta-Blocker Maintenance Dose in Patients with Heart Failure

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