Genotype-Guided Warfarin Therapy: Current Status

Abstract

Warfarin pharmacogenomics has been an extensively studied field in the last decades as it is focused on personalized therapy to overcome the wide interpatient warfarin response variability and decrease the risk of side effects. In this expert review, besides briefly summarizing the current knowledge about warfarin pharmacogenetics, we also present an overview of recent studies that aimed to assess the efficacy, safety and economic issues related to genotype-based dosing algorithms used to guide warfarin therapy, including randomized and controlled clinical trials, meta-analyses and cost-effectiveness studies. To date, the findings still present disparities, mostly because of standard limitations. Thus, further studies should be encouraged to try to demonstrate the benefits of the application of warfarin pharmacogenomic dosing algorithms in clinical practice.

Next-Generation Sequencing to Diagnose Suspected Genetic Disorders

“…44 However, studies of genotype-guided warfarin dosing -arguably one of the best-known pharmacogenomic exampleshave not yielded clear guidance. 45 Assessment of common-disease risk and other uses of genomic data in healthy persons needs to be performed with the use of high-quality scientific methods despite the temptation to move rapidly toward implementation. 46 In a study of genome sequence analysis involving healthy patients, 22% had a monogenic disease risk result with uncertain clinical usefulness.…”

Pharmaceutical Care Increases Time in Therapeutic Range of Patients With Poor Quality of Anticoagulation With Warfarin

“…A published meta-analysis showed that warfarin was able to reduce stroke events by approximately 60% in patients with AF ( Hart et al, 2007 ). Nevertheless, this pharmacotherapy presents a narrow therapeutic index, extensive drug and food interactions and large inter-individual variability in dose requirements, with intensive monitoring necessary to be effective and avoid adverse effects ( Wells et al, 1994 ; Wan et al, 2008 ; Guyatt et al, 2012 ; Soares et al, 2012 ; Santos et al, 2013 ; Marcatto et al, 2016b ; Tavares et al, 2018 ). In this sense, a study from Lip et al investigated the incidence and risk of adverse events in a real world setting in AF patients using warfarin.…”

<p>Influence of PSRC1, CELSR2, and SORT1 Gene Polymorphisms on the Variability of Warfarin Dosage and Susceptibility to Cardiovascular Disease</p>

“…20 The Clarification of Optimal Anticoagulation through Genetics (COAG) trial found no better outcomes using genotype-guided warfarin dosing in comparison to a clinical algorithmic approach. [31][32][33][34] However, a large proportion of the study population was African Americans, whose warfarin sensitivity polymorphisms were not included in genotyping. 35 The second review by Cavallari et al, published in 2017, revisited the debate with new evidence from the Genetics Informatics Trial (GIFT), which found that a 27% reduction in venous thromboembolism, hemorrhage, INR values >4, and death in the group that was doused with a genotype-guided approach.…”