Randomized controlled trial of genotype‐guided warfarin anticoagulation in Chinese elderly patients with nonvalvular atrial fibrillation

Abstract

What is known and objective Warfarin is an oral anticoagulant which has been widely used to treat and prevent thromboembolic events. Managing warfarin therapy requires careful monitoring and dose titration. This randomized controlled study was designed to assess the effect of genotype‐guided warfarin anticoagulation in Chinese elderly patients with nonvalvular atrial fibrillation. Methods 507 adults were randomized to receive initial dosing as determined by an algorithm containing genetic (VKORC1 and CYP2C9) plus clinical information or only clinical information. The primary endpoint was the time in therapeutic range (TTR) over 90 days. Secondary end points included haemorrhagic events, thrombotic events and mortality. Results The TTR was significantly different between genetic group and control group. The average TTR was (70.80 ± 24.39) % in the genotype‐guided group as compared with (53.44 ± 26.73) % in the control group. This represents a difference of 17.36% (95% CI, 11.82 to 22.89, P < .001). The cumulative incidence of total haemorrhagic events, minor haemorrhagic events, gastrointestinal bleeding and intracerebral bleeding events was not significantly different between two groups (P > .05). Follow‐up showed that the cumulative incidence of ischaemic stroke events occurred in the genetic group was significantly lower than that in the control group (2.39% vs 6.82%), and the genetic group had a significant lower risk than control group in cumulative incidence of ischaemic stroke events [HR 0.22, (95% CI 0.065 to 0.77), P < .05]. What is new and conclusion Genotype‐guided dosing could improve the average TTR, and follow‐up result showed that genotype‐guided therapy resulted in a significantly lower risk of ischaemic stroke events. Further research is required to focus on the clinical benefit of genotype‐guided dosing.

Ethnic Diversity and Warfarin Pharmacogenomics

“…In this trial that recruited Chinese patients with heart valve replacement, genotype-guided dosing reduced the number of days to reach therapeutic INR (genotype-guided dosing vs. clinically-guided dosing, 3.8 ± 2 vs. 4.4 ± 2, p < 0.001) although there was no reduction in major bleeding or thrombotic events. Two other recent relatively-large trials, respectively, randomized 660 and 507 patients and both reported that genotype-guided dosing was better than clinically-guided dosing in terms of the PTTR [respective mean differences 5.6 (95% CI 1.1 to 10.2, p = 0.01) and 17.4 (95% CI 11.8 to 22.9, p < 0.01)] ( Zhu et al, 2020b ; Guo et al, 2020 ). These trials together with other Chinese trials recruited 4,858 patients or 88% of all Asian participants meaning other Asian countries/non-Chinese populations are currently underrepresented.…”

A retrospective cohort study of pharmacogenetics of warfarin dosing in Chinese Adults with nonvalvular atrial fibrillation

“…Despite extensive researches, warfarin dosing and its relationship with gene polymorphisms remain an unresolved problem in China [9].Genotype-guided warfarin dosing that could improve the average TTR were published in 2020, however, there is still no nal consensus yet on the bene ts of genotype-guided warfarin dosing in clinical practice and the guide for the use of genotypeguided warfarin dosing in patients for the treatment of AF is still lacking. Larger clinical studies are still required to validate whether genotype-guided dosing improves such outcomes [10]. Therefore, we assessed two genes (CYP2C9*3 and VKORC1c.1639G > A) which may in uence warfarin drug response and evaluate whether genotype-guided warfarin dosing is superior to routine clinical use in Chinese patients with nonvalvular AF.…”

Role of Rivaroxaban in the Antithrombotic Treatment of Patients with Coronary Heart Disease and Atrial Fibrillation after Percutaneous Coronary Intervention

“…As a traditional anticoagulant, warfarin has a significant anticoagulant effect, but it is required to monitor the INR regularly to adjust the dose during use and it is easily affected by food, drugs, etc., which leads to a higher incidence of clinical bleeding. As a NOAC and an inhibitor of coagulation factor Xa, rivaroxaban selectively blocks the active site of factor Xa and exerts its anticoagulant effect [12,13] . With a stable anticoagulation effect, it neither needs to monitor coagulation function nor will be affected by food or drugs.…”