Clinical Pharmacy Cardiac Risk Service, Kaiser Permanente, Aurora, CO, USA.
J Thromb Thrombolysis. 2011 May;31(4):472-7. doi: 10.1007/s11239-010-0535-8.
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.
通常情况下，会监测国际标准化比值（INR），并在华法林治疗期间与泼尼松等相互作用的药物开始使用后，必要时调整华法林剂量以纠正非治疗性 INR。另一种方法是预防性调整华法林剂量。本研究旨在评估在泼尼松-华法林联合使用时，预防性调整华法林剂量预防非治疗性 INR 的效果。患者被随机分为两组，一组在华法林-泼尼松联合使用后 72 小时内进行 10%至 20%的预防性华法林剂量减少（干预组），另一组进行反应性华法林剂量调整（对照组）。受试者在 7 天内接受了一次随访 INR。主要结局是随访 INR 超过 INR 目标范围上限 1 点。次要结局包括 INR 控制情况、处方维生素 K 的购买情况以及泼尼松开始后 30 天内的华法林相关不良事件。干预组和对照组分别有 20 例和 17 例患者。干预组的华法林剂量中位数减少了 11.8%。与对照组（5 例）相比，更多的对照组患者（n = 5）的 INR 超过 INR 目标范围上限 1 点；然而，实际差异（29.4%比 10.0%）没有统计学意义（P = 0.21）。与对照组相比，干预组有更多的患者 INR 处于亚治疗范围（40%比 5.9%，P = 0.02）。两组各有 1 例患者发生华法林相关出血。未观察到血栓栓塞并发症或维生素 K 的购买。对于开始泼尼松治疗的患者，与 INR 监测并进行反应性华法林剂量调整相比，预防性华法林剂量减少可降低超治疗性 INR 的发生率，但增加了亚治疗性 INR 的可能性。
