Optimizing Time in Therapeutic Range in Patients With HeartMate 3: Pharmacist-Led Anticoagulation Using Pharmacogenetics of Warfarin

Background: Suboptimal time in therapeutic range (TTR) during warfarin anticoagulation is frequently observed in patients supported with a left ventricular assist device (LVAD) HeartMate 3 (HM3). Reduced TTR is associated with an increased risk of bleeding and thromboembolic events. Objective: To demonstrate that combining warfarin pharmacogenetic testing before warfarin initiation with warfarin management led by clinical pharmacists increases TTR of patients with LVAD HM3 compared with the usual care provided by physicians. Methods: This research was conducted as a single-center, prospective, randomized, controlled, and unblinded study. Patients were randomized into either an intervention group (IG) or a control group (CG). Before warfarin initiation, pharmacogenetic screening for CYP2C9*2, CYP2C9*3, and VKORC1 were performed in the IG. The management of anticoagulation with warfarin was then led by clinical pharmacists. In the CG, both warfarin dosing and the overall anticoagulation management were supervised by physicians and the results of genetic testing were kept blinded. The primary objective was to compare the TTR between the study groups within 12 weeks following the warfarin initiation. Results: Forty-eight patients were enrolled into the study. Eighteen in the IG and 23 in the CG completed the study. The baseline characteristics and distribution of genetic polymorphism of warfarin were similar between the groups. The TTR was 78.1% for IG and 67.1% for CG ( P < 0.05). Conclusion and Relevance: The pharmacist-led warfarin management with knowledge of pharmacogenetics of warfarin resulted in significantly higher TTR in patients with LVAD HM3 compared with the usual care represented by the attending physicians.