Toward Personalized Anticoagulation: Clinical Predictors of Early Warfarin Response in Heart Valve Replacement Patients

<b>Background/Objective</b>: Warfarin is the standard anticoagulant for patients with mechanical heart valve replacement (HVR). However, its narrow therapeutic index and interpatient variability complicate early postoperative management. Evidence on how valve position influences warfarin sensitivity is limited. This study evaluated the impact of prosthetic valve position and clinical factors on early warfarin response and developed a prediction model to guide initial warfarin dosing in HVR patients. <b>Methods</b>: A retrospective study was conducted on 310 adults who underwent mechanical aortic, mitral, or double valve replacement at Hamad Medical Corporation (2015-2022). Warfarin was initiated within 24 h postoperatively, and patients were monitored for three days. Outcomes included daily warfarin dose, international normalized ratio (INR) levels, attainment of therapeutic INR, INR overshoot (≥4), and the warfarin dose index on day 3 (WDI3). Predictors of WDI3 were analyzed using multivariable regression, and a LASSO model was applied to a dose prediction algorithm for the day 1 dose. <b>Results</b>: Mitral valve recipients required lower doses than aortic or double valve groups (<i>p</i> = 0.008) but had higher INR overshoot rates (18.75% vs. 16.05% and 4.55%; <i>p</i> = 0.033). Female sex and a higher baseline INR were associated with greater sensitivity (<i>p</i> < 0.01), whereas mitral/double valve position predicted reduced sensitivity (<i>p</i> = 0.010). Only half of the cohort reached therapeutic INR by day 3. The prediction model explained ~28% of dose variance with moderate performance. <b>Conclusions</b>: Valve position, sex, and baseline INR significantly influence early postoperative warfarin response. Incorporating these clinical factors into dosing algorithms may optimize initial warfarin management in HVR patients.