Evaluation of inter-patient variability in the pharmacodynamic indices of warfarin

Warfarin exhibits huge inter-individual variability in therapeutic response. We assessed the extent and the factors affecting inter-individual variability in the anticoagulation control using pre-validated pharmacodynamic indices.

Patients receiving warfarin for at least 6 months were recruited. CHA₂DS₂-VASc, HASBLED, SAMe-TT2R2 scores, warfarin sensitive index (WSI), log-INR variability, and warfarin composite measure (WCM) were assessed. National Institute for Health and Care Excellence (NICE) guideline was adhered for assessing the anticoagulation control using time in therapeutic range (TTR) (TTR < 65%-poor; and TTR ≥ 65%-good). Odds ratio [95% confidence interval] was the effect estimate measure.

Eighty-seven (39.5%) of the patients were poorly anticoagulated. Those with lower HASBLED [OR: 0.3; 0.1, 0.6] and SAMe-TT2R2 scores [OR: 0.2; 0.04, 0.7] and higher CHA₂DS₂-VASc score [OR: 1.8; 1.1, 1.3] predicted good anticoagulation control. Thirty-five (15.9%) patients had high INR variability. Lower TTR, shorter duration of therapy, and higher WSI were observed in patients with high INR variability, and presence of drugs with potential interaction significantly predicted high INR variability.

Significant numbers of our patients on warfarin had poor anticoagulation control and high INR variability. We have identified duration of therapy, CHA₂DS₂-VASc score, and WSI as reliable predictors for anticoagulation control and INR variability.