Genotype-Guided Warfarin Dosing in Patients With Mechanical Valves: A Randomized Controlled Trial

Yee

et al. 2020

Sci Rep

Byung chul chang 4,5 ✉ & Hye Sun Gwak 2 ✉ This prospective, single-blind, randomized study was designed to evaluate the effect of genotypebased warfarin dosing compared with standard warfarin dosing in Korean patients with mechanical cardiac valves. patients were assigned to either the genotype-based dosing group or the standard dosing group using stratified block randomization. The genotype-based dosing equation was adopted from a previous study which included VKORC1 rs9934438, CYP2C9 rs1057910, CYP4F2 rs2108622, and age. primary outcomes included the percentage of time in the therapeutic range (pttR): (i) during the first week following initiation of warfarin therapy, (ii) during hospitalization and (iii) until the first outpatient visit. A total of 91 patients were included in the analysis, 42 treated with genotype-based warfarin dosing and 49 treated with standard warfarin dosing. The genotype frequency differences of the three SNPs included in this study (ie, VKORC1, CYP2C9, CYP4F2), between the genotype-based dosing and standard dosing groups were not different. The genotype-based dosing group trended toward higher pTTR when compared with the standard dosing group, although this difference was not statistically significant. In patients with aortic valve replacement, TTR traditional and ttR Rosendaal were significantly higher in the genotype-based dosing group when compared with the standard dosing group during the first week following treatment initiation [ie, 58.5% vs. 38.1% (p = 0.009) and 64.0% vs. 44.6% (p = 0.012), respectively]. Based on the results, the genotype-guided dosing did not offer a significant clinical advantage, but a possible benefit in patients with aortic valve replacement has been suggested.

Section: Discussionsupporting

confidence: 86%

Genotype-guided warfarin dosing may benefit patients with mechanical aortic valve replacements: randomized controlled study

Yee

et al. 2020

Sci Rep

“…Subsequently, GBWD had less of an effect on anticoagulation control, and multiple-dose titrations might have had a greater role. The finding that the TTR was shorter in the GBWD group is similar to that observed in the GIFT, EU-PACT, and COUMAGEN-II trials Wen et al, 2017) but different from that in the COAG study and other Asian-based studies Gage et al, 2017;Syn et al, 2018;Zhe et al, 2018). Our study revealed that GBWD resulted in a lower prevalence of bleeding events related to anticoagulation therapy, which may have been due to superior primary outcomes.…”

Section: Discussionsupporting

confidence: 73%

Effect of Gene-Based Warfarin Dosing on Anticoagulation Control and Clinical Events in a Real-World Setting

Zhang

Wang

et al. 2020

Front. Pharmacol.

The cytochrome P450 2C9 and vitamin K epoxide reductase complex subunit 1 genotypes are associated with anticoagulation control and the clinical events in warfarin therapy. However, the clinical utility of gene-based warfarin dosing (GBWD) is controversial. We compared the anticoagulation control and clinical events related to warfarin with GBWD to those with clinically fixed dosing (CFD). A retrospective cohort study was conducted in a real-world setting. Of the 915 patients who were reviewed, 844 patients met the study-entry criteria; 413 cases were guided by GBWD using the International Warfarin Pharmacogenetic Consortium algorithm; 431 cases were guided by CFD (2.5 mg/day). The primary outcomes were the time needed to achieve the therapeutic International Normalized Ratio (INR) and the time in the therapeutic range (TTR) during a 3-month timeframe. The time needed to achieve the therapeutic INR (in days) for patients in the GBWD group was shorter than that for patients in the CFD group (10.21 ± 4.68 vs. 14.31 ± 8.26, P < 0.001). The overall TTR (Day 4-90) was significantly different between the GBWD group and CFD group (56.86 ± 10.72 vs. 52.87 ± 13.92, P = 0.007).In subgroup analysis, the TTR was also significantly different between the GBWD group and CFD group during the first month of treatment (Day 4-14: 54.28 ± 21.90 vs. 47.01 ± 26.25, P = 0.012; Day 15-28: 59.60 ± 20.12 vs. 51.71 ± 18.96, P = 0.001). However, no significant difference in the TTR was observed after 29 days of treatment. These data suggest that GBWD provided clinical benefits.

European Heart Journal - Cardiovascular Pharmacotherapy

“…age, body mass index, smoking, interacting drugs, collectively <20%) [24][25][26]. At least 14 clinical trials testing genotype-guided warfarin dosing have been conducted, employing various algorithms that incorporate genetic (VKORC1, CYP2C9 +/-CYP4F2) and clinical covariates 25,27,28 . The largest European RCT of warfarin PGx was conducted by the EU-PACT collaboration and recruited patients starting warfarin for atrial fibrillation or venous thromboembolism (VTE) 29 .…”

Section: Anticoagulants Warfarin and Other Vitamin K Antagonistsmentioning

confidence: 99%

The role of pharmacogenomics in contemporary cardiovascular therapy: a position statement from the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy

Magavern

Kaski

Turner

et al. 2021

There is a strong and ever-growing body of evidence regarding the use of pharmacogenomics to inform cardiovascular pharmacology. However, there is no common position taken by international cardiovascular societies to unite diverse availability, interpretation and application of such data, nor is there recognition of the challenges of variation in clinical practice between countries within Europe. Aside from the considerable barriers to implementing pharmacogenomic testing and the complexities of clinically actioning results, there are differences in the availability of resources and expertise internationally within Europe. Diverse legal and ethical approaches to genomic testing and clinical therapeutic application also require serious thought. As direct-to-consumer genomic testing becomes more common, it can be anticipated that data may be brought in by patients themselves, which will require critical assessment by the clinical cardiovascular prescriber. In a modern, pluralistic and multi-ethnic Europe, self-identified race/ethnicity may not be concordant with genetically detected ancestry and thus may not accurately convey polymorphism prevalence. Given the broad relevance of pharmacogenomics to areas such as thrombosis and coagulation, interventional cardiology, heart failure, arrhythmias, clinical trials, and policy/regulatory activity within cardiovascular medicine, as well as to genomic and pharmacology subspecialists, this position statement attempts to address these issues at a wide-ranging level.