1.
Non-Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Patients with Atrial Fibrillation with Coronary or Peripheral Artery Disease.
Zhang, H, Xue, Z, Yi, D, Li, X, Tan, Y, Li, J
International heart journal. 2020;(2):231-238
Abstract
The efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) with coronary or peripheral artery disease (CAD or PAD) remain largely unresolved. We, therefore, conducted a meta-analysis to explore the effect of NOACs compared with warfarin in these populations.We systematically searched the Cochrane Library, PubMed, and Embase databases for randomized controlled trials (RCTs) involving NOACs versus warfarin in AF patients with CAD or PAD. A random-effect model was selected to pool the risk ratios (RRs) and 95% confidence intervals (CIs).A total of 7 RCTs were included. In AF patients with CAD, compared with warfarin use, the use of NOACs was associated with reduced risks of stroke/systemic embolism (RR 0.82; 95% CI 0.70-0.96) and intracranial hemorrhage (RR 0.41; 95% CI 0.26-0.63), but NOACs versus warfarin showed similar risks of all-cause death (RR 0.95; 95% CI 0.86-1.05), cardiovascular death (RR 0.95; 95% CI 0.80-1.13), stroke (RR 0.80; 95% CI 0.64-1.00), myocardial infarction (RR 1.00; 95% CI 0.83-1.21), and major bleeding (RR 0.82; 95% CI 0.65-1.04). Among patients with AF and PAD, NOACs versus warfarin had similar risks for stroke (RR 0.93; 95% CI 0.61-1.42), myocardial infarction (RR 1.10; 95% CI 0.64-1.90), all-cause death (RR 0.91; 95% CI 0.70-1.19), major bleeding (RR 1.12; 95% CI 0.70-1.81), and intracranial hemorrhage (RR 0.54; 95% CI 0.16-1.85).NOACs seem to be at least as effective and safe as warfarin in AF patients with CAD. whereas NOACs versus warfarin have similar efficacy and safety in patients with PAD.
2.
Identification of novel variants associated with warfarin stable dosage by use of a two-stage extreme phenotype strategy.
Luo, Z, Li, X, Zhu, M, Tang, J, Li, Z, Zhou, X, Song, G, Liu, Z, Zhou, H, Zhang, W
Journal of thrombosis and haemostasis : JTH. 2017;(1):28-37
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Abstract
UNLABELLED Essentials Required warfarin doses for mechanical heart valves vary greatly. A two-stage extreme phenotype design was used to identify novel warfarin dose associated mutation. We identified a group of variants significantly associated with extreme warfarin dose. Four novel identified mutations account for 2.2% of warfarin dose discrepancies. SUMMARY Background The variation among patients in warfarin response complicates the management of warfarin therapy, and an improper therapeutic dose usually results in serious adverse events. Objective To use a two-stage extreme phenotype strategy in order to discover novel warfarin dose-associated mutations in heart valve replacement patients. Patients/method A total of 1617 stable-dose patients were enrolled and divided randomly into two cohorts. Stage I patients were genotyped into three groups on the basis of VKORC1-1639G>A and CYP2C9*3 polymorphisms; only patients with the therapeutic dose at the upper or lower 5% of each genotype group were selected as extreme-dose patients for resequencing of the targeted regions. Evaluation of the accuracy of the sequence data and the potential value of the stage I-identified significant mutations were conducted in a validation cohort of 420 subjects. Results A group of mutations were found to be significantly associated with the extreme warfarin dose. The validation work finally identified four novel mutations, i.e. DNMT3A rs2304429 (24.74%), CYP1A1 rs3826041 (47.35%), STX1B rs72800847 (7.01%), and NQO1 rs10517 (36.11%), which independently and significantly contributed to the overall variability in the warfarin dose. After addition of these four mutations, the estimated regression equation was able to account for 56.2% (R2Adj = 0.562) of the overall variability in the warfarin maintenance dose, with a predictive accuracy of 62.4%. Conclusion Our study provides evidence linking genetic variations in STX1B, DNMT3A and CYP1A1 to warfarin maintenance dose. The newly identified mutations together account for 2.2% of warfarin dose discrepancy.