Genotype-Guided vs Clinical Dosing of Warfarin and Its Analogues: Meta-Analysis of Randomized Clinical Trials

Study Questions:

Is genotype-guided initial dosing of warfarin better than clinic dosing protocols?


A meta-analysis of nine trials, including 2,812 patients initiating warfarin therapy, was performed. Primary outcomes examined included the percent time in the therapeutic range (TTR), the percent of international normalized ratio (INR) values >4, as well as the incidence of major bleeding and thromboembolism.


Across nine trials with variable follow-up (4 weeks to 6 months; median, 12 weeks), the mean TTR was not significantly different between the genotype-guided and clinical dosing protocol groups (difference, 14%; 95% confidence interval [CI], -10 to 39%; p = 0.25). The mean number of INR values >4 was 23.8% for genotype-guided patients versus 28.0% for clinical dosing patients (relative risk [RR], 0.92; 95% CI, 0.82-1.05; p = 0.21). Major bleeding occurred in 0.9% of genotype-guided patients versus 1.6% of clinical dosing patients (RR, 0.60; 95% CI, 0.29-1.22; p = 0.16). Thromboembolic events occurred in 1.1% of genotype-guided patients versus 1.2% of clinical dosing patients (RR, 0.97; 95% CI, 0.46-2.05; p = 0.93).


The authors concluded that there is no clinical benefit in terms of TTR, high INR values, bleeding, or thromboembolic events.


This meta-analysis helps us understand the results of two recently published, but somewhat conflicting trials on the use of genotype-guided warfarin dosing. In the COAG trial, there was no benefit to genotype-guided dosing, whereas the EU-PACT trial did show a benefit in TTR, but no benefit in clinical outcomes. Although the FDA has included information about the potential benefit of genotype testing for patients taking warfarin, this study confirms that such testing is not of benefit at the time of warfarin initiation. It is important to note that nearly all of the trials used a nomogram or algorithm for the clinical dosing patients in an effort to provide high-quality anticoagulation care. The one notable exception is the EU-PACT trial, which relied on usual local practice for the clinical dosing patients. Use of a validated tool is important for all providers, even if they only manage warfarin for a small number of patients.

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