Chinese Patients With Heart Valve Replacement Do Not Benefit From Warfarin Pharmacogenetic Testing on Anticoagulation Outcomes

Abstract

Background: Genotype-guided warfarin dosing has been shown in some randomized trials to improve anticoagulation outcomes in individuals of European ancestry; yet, its utility in Chinese patients with heart valve replacement remains unresolved. Methods: A total of 2264 patients who underwent heart valve replacement at Wuhan Asia Heart Hospital were enrolled in this study. Patients were randomly divided into 2 groups, namely, a genotype-guided and a traditional clinically guided warfarin dosing group. In the genotype-guided group (n = 1134), genotyping for CYP2C9 and VKORC1 (−1639 G→A) was performed using TaqMan genotyping assay. Warfarin doses were predicted with the International Warfarin Pharmacogenetics Consortium algorithm. Patients in the control group (n = 1130) were clinically guided. The primary outcome was to compare the incidence of adverse events (major bleeding and thrombotic) during a 90-day follow-up period between 2 groups. Secondary objectives were to describe effects of the pharmacogenetic intervention on the first therapeutic-target-achieving time, the stable maintenance dose, and the hospitalization days. Results: A total of 2245 patients were included in the analysis. Forty-nine events occurred during follow-up. Genotype-guided dosing strategy did not result in a reduction in major bleeding (0.26% versus 0.63%; hazard ratio, 0.44; 95% confidence interval, 0.13–1.53; P = 0.20) and thrombotic events (0.89% versus 1.61%; hazard ratio, 0.56; 95% confidence interval, 0.27–1.17; P = 0.12) compared with clinical dosing group. Compared with traditional dosing, patients in the genotype-guided group reached their therapeutic international normalized ratio in a shorter time (3.8 ± 2.0 versus 4.4 ± 2.0 days, P < 0.001). There was no difference in hospitalization days (P = 0.28). Conclusions: Warfarin pharmacogenetic testing according to the International Warfarin Pharmacogenetics Consortium algorithm cannot improve anticoagulation outcomes in Chinese patients with heart valve replacement.

Genotype‐guided warfarin therapy: Still of only questionable value two decades on

“…This finding is interesting since a recent study has also reported that CYP2C9 and VKORC1 genotype‐guided dosing of warfarin may be beneficial in patients diagnosed with AF but not in patients with deep vein thrombosis or pulmonary embolism . To complicate the matter, it has also been reported that there were no significant differences between the warfarin maintenance dosages in patients with AF, patients with heart valve replacement and those with both AF and heart valve replacement whereas in another study, pharmacogenetic testing did not improve anticoagulation outcomes in Chinese patients with valve replacement . These reports raise a question as to whether the benefits of genotype‐guided warfarin therapy, if any, may be sensitive to the indication for its use.…”

“…Apart from atrial fibrillation (AF), indications studied include stroke, prophylaxis associated with the use of artificial heart valves and continuous‐flow left ventricular assist devices, deep venous thrombosis and pulmonary embolism . Patients studied came from diverse ethnic/racial backgrounds and included not only adult but also paediatric populations …”

Correlation between Metabolic Parameters and Warfarin Dose in Patients with Heart Valve Replacement of Different Genotypes

“…Hao Y et al . [ 19 ] also suggested that warfarin pharmacogenetic testing according to the algorithm of the International Warfarin Pharmacogenetics Alliance did not improve the anticoagulation results of patients with heart valve replacement in China. This may be because the anticoagulant effect of warfarin is affected by drug metabolism, absorption and other factors.…”

Comparison of Warfarin Initiation at 3 mg Versus 5 mg for Anticoagulation of Patients with Mechanical Mitral Valve Replacement Surgery: A Prospective Randomized Trial

“…Published clinical trials have generated variable results regarding the benefit of genotype-guided warfarin dosing [32,41]. Some studies showed better safety [42] or shorter time to reach therapeutic INR [43] with genotype-guided warfarin, while others have highlighted the need to develop race-specific dosing algorithms [44,45]. However, further studies are still needed to determine the cost effectiveness of routine warfarin-related genotype testing [46].…”