Warfarin dosing algorithms: A systematic review

Aims: Numerous algorithms have been developed to guide warfarin dosing and improve clinical outcomes. We reviewed the algorithms available for various populations and the covariates, performances and risk of bias of these algorithms.

Methods: We systematically searched MEDLINE up to 20 May 2020 and selected studies describing the development, external validation or clinical utility of a multivariable warfarin dosing algorithm. Two investigators conducted data extraction and quality assessment.

Results: Of 10 035 screened records, 266 articles were included in the review, describing the development of 433 dosing algorithms, 481 external validations and 52 clinical utility assessments. Most developed algorithms were for dose initiation (86%), developed by multiple linear regression (65%) and mostly applicable to Asians (49%) or Whites (43%). The most common demographic/clinical/environmental covariates were age (included in 401 algorithms), concomitant medications (270 algorithms) and weight (229 algorithms) while CYP2C9 (329 algorithms), VKORC1 (319 algorithms) and CYP4F2 (92 algorithms) variants were the most common genetic covariates. Only 26% and 7% algorithms were externally validated and evaluated for clinical utility, respectively, with <2% of algorithm developments and external validations being rated as having a low risk of bias.

Conclusion: Most warfarin dosing algorithms have been developed in Asians and Whites and may not be applicable to under-served populations. Few algorithms have been externally validated, assessed for clinical utility, and/or have a low risk of bias which makes them unreliable for clinical use. Algorithm development and assessment should follow current methodological recommendations to improve reliability and applicability, and under-represented populations should be prioritized.