Implementation of genotype-guided dosing of warfarin with point-of-care genetic testing in three UK clinics: a matched cohort study

Abstract

Background Warfarin is a widely used oral anticoagulant. Determining the correct dose required to maintain the international normalised ratio (INR) within a therapeutic range can be challenging. In a previous trial, we showed that a dosing algorithm incorporating point-of-care genotyping information (‘POCT-GGD’ approach) led to improved anticoagulation control. To determine whether this approach could translate into clinical practice, we undertook an implementation project using a matched cohort design. Methods At three clinics (implementation group; n = 119), initial doses were calculated using the POCT-GGD approach; at another three matched clinics (control group; n = 93), patients were dosed according to the clinic’s routine practice. We also utilised data on 640 patients obtained from routinely collected data at comparable clinics. Primary outcome was percentage time in target INR range. Patients and staff from the implementation group also provided questionnaire feedback on POCT-GGD. Results Mean percentage time in INR target range was 55.25% in the control group and 62.74% in the implementation group; therefore, 7.49% (95% CI 3.41–11.57%) higher in the implementation group ( p = 0.0004). Overall, patients and staff viewed POCT-GGD positively, suggesting minor adjustments to allow smooth implementation into practice. Conclusions In the first demonstration of the implementation of genotype-guided dosing, we show that warfarin dosing determined using an algorithm incorporating genetic and clinical factors can be implemented smoothly into clinic, to ensure target INR range is reached sooner and maintained. The findings are like our previous randomised controlled trial, providing an alternative method for improving the risk-benefit of warfarin use in daily practice. Electronic supplementary material The online version of this article (10.1186/s12916-019-1308-7) contains supplementary material, which is available to authorized users.

Biomarker-guided trials: Challenges in practice

“…EU-PACT provides an example of an international, multi-site trial which, due to its pragmatic approach and adoption of the biomarker-strategy design allowed the improved treatment outcomes from using a biomarker-guided approach to prescribing warfarin to be demonstrated. This has led to a subsequent matched-cohort study which demonstrated the successful implementation of the biomarker-guided approach into clinical practice [18], and a trial based on EU-PACT is currently being planned in Africa to test the clinical utility of a personalised approach to warfarin dosing in low-resource settings.…”

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“…Clinicians have used genotype information as a guideline to help determine the correct dose of warfarin. 35 The Clinical Pharmacogenetics Implementation Consortium published genotype-based drug guidelines to help clinicians optimize drug therapies with genetic test results. 36 Genomic profiling of tumors can inform targeted therapy plans for patients with breast or lung cancer.…”

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“…Both CPIC [ 143 ] and DPWG have developed warfarin PGx guidelines for commencing warfarin that recommend validated genetic algorithms (e.g., the EU-PACT loading algorithm [ 15 ] or International Warfarin Pharmacogenetics Consortium (IWPC) algorithm [ 144 ]) or percent dose alterations. Importantly, point-of-care genotype-guided warfarin dosing has been shown to significantly improve TTR following implementation in real world anticoagulation clinics [ 145 ], and appears cost-effective [ 16 ].…”