A genotype-guided dosing (GD) strategy for warfarin was superior for efficacy outcomes and similar for safety outcomes compared with fixed dosing, according to a study published in Thrombosis Research.

The systematic review and meta-analysis was based on a literature search of PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to July 2021 for relevant randomized controlled trials of patients taking warfarin. The primary outcome was the percentage of time in therapeutic range (TTR) for less than or equal to 30 days and for greater than 30 days.

A total of 9906 patients from 27 studies were included—5071 patients in the GD group and 4835 patients in the non-GD group. The follow-up was 21 days to 360 days.


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For follow-up of less than or equal to 30 days, results from 14 studies showed that the GD group had a significantly increased TTR vs the non-GD group (mean difference [MD] 5.95; 95% CI, 2.41 to 9.49; P =.001; I2 = 87%). For the follow-up of greater than 30 days in 12 studies, a significant increase of TTR was observed in the GD group vs the non-GD group (MD 4.93; 95% CI, 1.40 to 8.47; P =.006; I2 = 78%).

Pooled meta-analysis of 7 studies showed a significantly reduced time to the first therapeutic international normalized ratio (INR) in the GD group vs the non-GD group (MD −1.80 days; 95% CI, −2.69 to −0.92; P <.0001; I2 = 92%).

The pooled meta-analysis of 14 studies revealed a significantly reduced time to reach a stable dose in the GD group vs the non-GD group (MD −5.08 days; 95% CI, −7.09 to −3.07; P <.00001; I2 = 96%).

Based on 12 studies, the GD group had a lower risk for major bleeding events vs the non-GD group (risk ratio [RR] 0.50; 95% CI, 0.33 to 0.75; P =.0008; I2 = 0%). Also, based on 13 studies, a significant reduction of total bleeding events was observed in the GD group vs the non-GD group (RR 0.83; 95% CI, 0.73 to 0.95; P =.006; I2 = 2%).

No difference was found in all-cause mortality between the GD group and the non-GD group, based on 7 studies (RR 0.75; 95% CI, 0.36 to 1.56; P =.44; I2 = 0%).

In subgroup analysis, only time to therapeutic INR was reduced for the GD approach vs the clinical adjusted dosing approach. However, the major bleeding risk was lower for the GD approach vs the clinical adjusted dosing regimen (RR 0.56; 95% CI, 0.36 to 0.89; P =.01; I2 = 25%), and no decrease was found in the fixed dosing regimen (RR 0.63; 95% CI, 0.35 to 1.12; P =.12; I2 = 20%).

According to subgroup analysis based on ethnicity, the GD strategy was associated with increased TTR after 30 days (MD 5.12; 95% CI, 3.16 to 7.08; P <.00001; I2 = 83%) and time to first therapeutic INR (MD −1.28; 95% CI, −2.09 to −0.48; P =.02; I2 = 87%) in Asian patients vs non-Asian patients.

Among several study limitations, high heterogeneities were found in most of the efficacy outcomes. Also, in the sensitivity analysis, the statistical significance of the small number of results was changed in some of the outcomes, and further analysis was not performed owing to limited data.

“Overall, in terms of the efficacy of treatment, the GD strategy was superior to the fixed dosing strategy, but it did not seem to be better than the clinical adjusted regimen,” the researchers stated. “According to ethnicity subgroup analysis, Asian patients might benefit more from genotype-guided dosing strategy compared to the non-Asian population.”

Reference

Wang X, Tang B, Zhou M, et al. Efficacy and safety of genotype-guided warfarin dosing versus non-genotype-guided warfarin dosing strategies: a systematic review and meta-analysis of 27 randomized controlled trials. Thromb Res. Published online February 1, 2022. doi:10.1016/j.thromres.2021.12.023