Kaiser Permanente Washington, Tacoma, WA, USA.
Kaiser Permanente Colorado, 16601 East Centretech Parkway, Aurora, CO, 80011, USA.
J Thromb Thrombolysis. 2018 Aug;46(2):264-270. doi: 10.1007/s11239-018-1664-8.
Several drug interaction compendia report a risk of warfarin potentiation after initiation of a fibrate; however, the evidence of this interaction is limited. The objective of this study was to evaluate warfarin dose and international normalized ratio (INR) response among a large sample of patients receiving chronic warfarin who initiated a fibrate. This was a retrospective, one-sample, pre-to-post study. Adult patients who were receiving chronic warfarin therapy at the time of gemfibrozil or fenofibrate dispensing between 1/1/2000 and 3/31/2016 were included. Patients had at least one and two therapeutic INRs during the 90 days prior to (baseline) and after (follow-up), respectively, fibrate initiation. Comparison of stable warfarin dose:INR ratio between the baseline and follow-up periods and assessment of safety outcomes during follow-up were performed. There were 321 patients included. Patients were predominantly male (62.6%) with an indication of atrial fibrillation (44.2%). The mean warfarin dose:INR ratio was equivalent between the baseline and follow-up periods (13.4 mg/INR [± 6.9] vs. 13.5 mg/INR [± 7.5], respectively, p = 0.711). Rates of thromboembolism, bleeding, and all-cause mortality in the 90-day follow up were 0, 0.6, and 1.2%, respectively. Although individual patients may have labile INRs after fibrate initiation, no significant interaction between fibrate and warfarin in a large sample of real world patients was identified. The utility of additional INR monitoring after fibrate initiation in otherwise stable patients receiving chronic warfarin therapy is unclear.
几种药物相互作用手册报告称，在开始使用贝特类药物后，华法林的作用会增强；然而，这种相互作用的证据有限。本研究的目的是评估在开始使用贝特类药物时正在接受慢性华法林治疗的大量患者中，华法林剂量和国际标准化比值（INR）的反应。这是一项回顾性、单样本、用药前至用药后的研究。纳入了在 2000 年 1 月 1 日至 2016 年 3 月 31 日期间，开始使用吉非贝齐或非诺贝特时正在接受慢性华法林治疗的成年患者。患者在开始使用贝特类药物之前的 90 天内（基线）和之后（随访），至少有一次和两次治疗性 INR。比较了基线期和随访期稳定的华法林剂量：INR 比值，并在随访期间评估了安全性结果。共纳入 321 例患者。患者主要为男性（62.6%），心房颤动（44.2%）为主要适应证。基线期和随访期的华法林剂量：INR 比值相当（分别为 13.4 mg/INR [±6.9]和 13.5 mg/INR [±7.5]，p=0.711）。在 90 天随访期间，血栓栓塞、出血和全因死亡率分别为 0、0.6%和 1.2%。尽管个别患者在开始使用贝特类药物后 INR 可能不稳定，但在大量真实世界患者中未发现贝特类药物与华法林之间存在显著相互作用。在开始使用贝特类药物后，对于接受慢性华法林治疗且病情稳定的患者，是否需要额外监测 INR 尚不清楚。
