Empiric warfarin dose adjustment with prednisone therapy. A randomized, controlled trial

Abstract

Typically, the international normalized ratio (INR) is monitored and warfarin dose adjusted, if necessary, to correct non-therapeutic INR after interacting medications, like prednisone, are initiated during warfarin therapy. Preemptively adjusting the warfarin dose is another approach. To evaluate the utility of preemptive warfarin dosage adjustment for preventing non-therapeutic INR following prednisone-warfarin co-administration. Patients were randomized to either a preemptive warfarin dose reduction between 10 and 20% (intervention) or reactive warfarin dose adjustment (control) within 72 h of warfarin-prednisone co-administration. Subjects received a follow-up INR within 7 days. Primary outcome was the occurrence of follow-up INR ≥ 1 point over the INR goal range upper limit. Secondary outcomes included INR control, purchases of prescription vitamin K, and warfarin-associated adverse events in the 30 days after prednisone initiation. Twenty and 17 patients comprised the intervention and control groups. The intervention group’s warfarin dose was reduced by a median of 11.8%. More control patients (n = 5) experienced an INR ≥ 1 point over the INR goal range upper limit compared to intervention (n = 2); however, the actual difference (29.4 vs.10.0%) was not statistically significant (P = 0.21). A higher percentage of intervention patients had a subtherapeutic follow-up INR compared to control (40 vs. 5.9%, P = 0.02). One patient from each group experienced warfarin-associated bleeding. No thromboembolic complications or vitamin K purchases were observed. For patients initiating prednisone therapy, preemptive warfarin dose reduction resulted in a non-significant reduction in supratherapeutic INR but increased the likelihood of subtherapeutic INR compared to INR monitoring with reactive warfarin dose adjustment.