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

Zhu, Ye; Xu, Chao; Liu, Jia

doi:10.1111/jcpt.13218

Cited by 8 publications

(5 citation statements)

References 23 publications

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“…A further 46 studies were then excluded due to their inclusion of AF patients with other comorbidities or trials that were incomplete. Ultimately, a Meta-analysis was conducted with 11 studies, all of which were RCT [13,21,22,23,24,25,26,27,28], encompassing 70,801 patients comparably divided between two groups (NOACs and Warfarin). The study involved a total of 37,010 patients in the NOAC group, while the Warfarin group comprised 33,791 patients.…”

Section: Resultsmentioning

confidence: 99%

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Safety and Efficacy of Novel Oral Anticoagulants as Compared to Warfarin in Treatment of Atrial Fibrillation

et al. 2023

IJFMR

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BACKGROUND - Novel oral anticoagulants (NOACs) are a class of medications used to prevent blood clots thereby various studies have demonstrated their potential benefit in their use in atrial fibrillation. They act by inhibiting clotting factors such as factor Xa or Thrombin. Unlike traditional anticoagulants like Vitamin K antagonist (Warfarin), NOACs have a more predictable effect and require less frequent monitoring. OBJECTIVE – We aim to explore the safety and efficacy of Novel oral anticoagulants as compared to warfarin in the treatment of atrial fibrillation. Additionally, a comparative analysis among NOACs was conducted to determine the most superior among them. METHODS – We performed a pairwise systematic review in patients with atrial fibrillation undergoing anticoagulation with the help of NOAC as compared to those undergoing anticoagulation on Warfarin by analyzing various electronic databases from 2005 till 2023 and filtered 11 studies having 70,801 sample size distributed comparably among the two groups based on our inclusion criteria. RESULTS – There was a slight difference between the safety and efficacy of the NOAC and Warfarin groups. Among the participants, 3019 individuals (8.93%) who were administered Warfarin experienced major bleeding complications, in contrast to 2690 participants (7.26%) who were on NOACs. Regarding the occurrence of stroke, the Warfarin group observed a rate of 987 cases (2.92%), while the NOAC group had 1119 instances (3.02%) of stroke. CONCLUSION – The results of recent NOACs studies emphasizes on the superiority of them as compared to warfarin in both rapid onset of action as well as better patient compliance. Our review suggests a lower risk of bleeding but a slightly higher risk of stroke occurrence in NOACs as compared to the Warfarin group, thereby showing their superiority in clinical utility, though more robust clinical trials are required to establish long-term benefits.

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Section: Resultsmentioning

confidence: 99%

“…The remaining two trials were solely focussed on Warfarin. Zhu Y et.al [25] demonstrated 0.98% stoke rate and 3.55 % bleeding rate, whereas JG Cho et.al [24] showed 1.29 % stoke rate and 1.46 % bleed rate.…”

Section: Discussionmentioning

confidence: 97%

Safety and Efficacy of Novel Oral Anticoagulants as Compared to Warfarin in Treatment of Atrial Fibrillation

et al. 2023

IJFMR

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“…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.…”

Section: Clinical Utility Studiesmentioning

confidence: 99%

Ethnic Diversity and Warfarin Pharmacogenomics

Asiimwe

Pirmohamed

2022

Front. Pharmacol.

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Warfarin has remained the most commonly prescribed vitamin K oral anticoagulant worldwide since its approval in 1954. Dosing challenges including having a narrow therapeutic window and a wide interpatient variability in dosing requirements have contributed to making it the most studied drug in terms of genotype-phenotype relationships. However, most of these studies have been conducted in Whites or Asians which means the current pharmacogenomics evidence-base does not reflect ethnic diversity. Due to differences in minor allele frequencies of key genetic variants, studies conducted in Whites/Asians may not be applicable to underrepresented populations such as Blacks, Hispanics/Latinos, American Indians/Alaska Natives and Native Hawaiians/other Pacific Islanders. This may exacerbate health inequalities when Whites/Asians have better anticoagulation profiles due to the existence of validated pharmacogenomic dosing algorithms which fail to perform similarly in the underrepresented populations. To examine the extent to which individual races/ethnicities are represented in the existing body of pharmacogenomic evidence, we review evidence pertaining to published pharmacogenomic dosing algorithms, including clinical utility studies, cost-effectiveness studies and clinical implementation guidelines that have been published in the warfarin field.

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“…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.…”

Section: Introductionmentioning

confidence: 99%

Pharmacogenetics of warfarin dosing in Chinese adults with nonvalvular atrial fibrillation

Zhu

You²,

et al. 2023

Eur J Clin Pharmacol

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Background: The guide for the use of genotype-guided warfarin dosing in patients for the treatment of non-valvular atrial fbrillation (NVAF) is still lacking.Aim: We aimed to evaluate whether genotype-guided warfarin dosing is superior to conventional clinical dosing for the outcomes of interest in Chinese patients.Method: The patients of this study were assigned to two cohorts to receive their dose of warfarin determined by a genetic and clinical factor (gene group) or dosing determined empirically(control group).We incorporated CYP2C9 and VKORC1 genotypes into the gene group. The international normalized ratio (INR) measurement and standard protocols were used for further dose adjustment in both groups. The primary outcomes were the percentage of time in the therapeutic range (%TTR) and INR measurement during follow up. Secondary safety outcome included bleeding and thrombotic events.Results: Compared with the control group, the average TTR of the gene group was higher(68.4 ± 20.6) % vs (48.5 ± 21.6) %, P<0.001) .The frequency of the average INR monitoring times of the gene group was lower(P=0.02).At the end of follow-up, the gene group had a signi cant lower risk of cumulative incidences of ischemic stroke events in the adjusted model [relative risk (RR) 0.4 (95% CI 0.2 to 0.8),P =0.008] than control group. Conclusion: Genotype-guided warfarin administration increases the average TTR, reach higher TTR levels in the early anticoagulant phase and signi cantly reduce the risk of ischemic stroke events. Impact Statements• The utility of genotype-guided dosing of warfarin can optimize individual warfarin dosing in Chinese AF patients.• Genotype-guided warfarin administration increases the average TTR, reach higher TTR levels in the early anticoagulant phase and signi cantly reduce the risk of ischemic stroke events.

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

Cited by 8 publications

References 23 publications

Safety and Efficacy of Novel Oral Anticoagulants as Compared to Warfarin in Treatment of Atrial Fibrillation

Safety and Efficacy of Novel Oral Anticoagulants as Compared to Warfarin in Treatment of Atrial Fibrillation

Ethnic Diversity and Warfarin Pharmacogenomics

Pharmacogenetics of warfarin dosing in Chinese adults with nonvalvular atrial fibrillation

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