Purpose: Interpatient variation of warfarin dose requirements may be explained by genetic variations and general and clinical factors. In this scenario, diverse population-calibrated dosing algorithms, which incorporate the main warfarin dosing influencers, have been widely proposed for predicting supposed warfarin maintenance dose, in order to prevent and reduce adverse events. The aim of the present study was to evaluate the impact of the inclusion of ABCB1 c.3435C>T and CYP4F2 c.1297G>A polymorphisms as additional covariates in a previously developed pharmacogenetic-based warfarin dosing algorithm calibrated for the Brazilian population.
Methods: Two independent cohorts of patients treated with warfarin (n = 832 and n = 133) were included for derivation and replication of the algorithm, respectively. Genotyping of ABCB1 c.3435C>T and CYP4F2 c.1297G>A polymorphisms was performed by polymerase chain reaction followed by melting curve analysis and TaqMan® assay, respectively. A multiple linear regression was performed for the warfarin stable doses as a dependent variable, considering clinical, general, and genetic data as covariates.
Results: The inclusion of ABCB1 and CYP4F2 polymorphisms was able to improve the algorithm's coefficient of determination (R) by 2.6%. In addition, the partial determination coefficients of these variants revealed that they explained 3.6% of the warfarin dose variability. We also observed a marginal improvement of the linear correlation between observed and predicted doses (from 59.7 to 61.4%).
Conclusion: Although our study indicates that the contribution of the combined ABCB1 and CYP4F2 genotypes in explaining the overall variability in warfarin dose is not very large, we demonstrated that these pharmacogenomic data are statistically significant. However, the clinical relevance and cost-effective impact of incorporating additional variants in warfarin dosing algorithms should be carefully evaluated.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1007/s00228-018-2528-z | DOI Listing |
J Clin Med
December 2024
Division of Cardiology, Department of Medicine, NewYork-Presbyterian Hospital-Weill Cornell Medicine, New York, NY 10021, USA.
Thrombosis is an important cause of morbidity and mortality worldwide. Pregnancy is a hypercoagulable state, and thrombotic complications in pregnancy are a major cause of maternal and fetal morbidity and mortality. Current guidelines support the selective use of aspirin, heparin, and warfarin in pregnant women.
View Article and Find Full Text PDFJ Pharm Pract
January 2025
Boston Medical Center, Boston, MA, USA.
A case of enoxaparin-induced bullous hemorrhagic dermatosis is reported. A 69-year-old male with past medical history including chronic atrial fibrillation and a re-do aortic valve replacement, anticoagulated on warfarin, received an enoxaparin bridge for a molar extraction. On day 7 after restarting enoxaparin post-procedure at a therapeutic dose of 90 mg every 12 hours, the patient noticed multiple small, dark, raised lesions on his forearm and ankle.
View Article and Find Full Text PDFSr Care Pharm
January 2025
Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, California.
This review summarizes recent case reports where the consumption of dietary supplements by older adults may have caused an adverse event. In December 2023, PubMed was surveyed for case reports published from 2000 onwards, using two medical subject heading (MeSH) terms, "aged" and "dietary supplements," where the latter was combined with the MeSH subheadings "adverse effects," "poisoning," or "toxicity." Major clinical trials for dietary supplements were identified at
Sci Rep
December 2024
Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China.
Warfarin is the most widely used oral anticoagulant in clinical practice. The cytochrome P450 2C9 (CYP2C9), vitamin K epoxide reductase complex 1 (VKORC1), and cytochrome P450 4F2 (CYP4F2) genotypes are associated with warfarin dose requirements in China. Accurate genotyping is vital for obtaining reliable genotype-guided warfarin dosing information.
View Article and Find Full Text PDFCardiol Ther
December 2024
Internal Medicine Medical Affairs, Pfizer Japan Inc, 3-22-7 Yoyogi, Shibuya-Ku, Tokyo, 151-8589, Japan.
Introduction: Very elderly patients with nonvalvular atrial fibrillation (NVAF) are at high risk for both ischemic and hemorrhagic events. This study aimed to understand the characteristics and real-world treatment of very elderly patients with NVAF in Japan.
Methods: We conducted a retrospective analysis of electronic health records and claims data from acute care hospitals for very elderly patients with NVAF with medical records available on or after their 80th birthday.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!