Clark Nathan P, Witt Daniel M, Delate Thomas, Trapp Melissa, Garcia David, Ageno Walter, Hylek Elaine M, Crowther Mark A
Clinical Pharmacy Anticoagulation Service, Kaiser Permanente Colorado, 280 Exempla Circle, Lafayette, CO 80026, USA.
Pharmacotherapy. 2008 Aug;28(8):960-7. doi: 10.1592/phco.28.8.960.
To quantify the absolute risk of thromboembolism associated with a significant subtherapeutic international normalized ratio (INR) in patients with previously stable anticoagulation while receiving warfarin.
Retrospective, matched cohort analysis.
Centralized anticoagulation service in an integrated health care delivery system.
A total of 2597 adult patients receiving warfarin from January 1998-December 2005; 1080 patients were in the low INR cohort and were matched to 1517 patients in the therapeutic INR cohort based on index INR date, indication for warfarin, and age.
Stable, therapeutic anticoagulation was defined as two INR values, measured at least 2 weeks apart, within or above the therapeutic range. The low INR cohort included patients with a third INR value of 0.5 or more units below their therapeutic range. The therapeutic INR cohort included patients with a third therapeutic INR value and no INR value 0.2 or more units below their target INR range in the ensuing 90 days. The primary outcome was anticoagulation-related thromboembolism during the 90 days after the index INR. Secondary outcomes were times to the first occurrence of anticoagulation-related complications (bleeding, thromboembolism, or death) in the 90 days after the index INR. Four thromboembolic events (0.4%) occurred in the low INR cohort and one event (0.1%) in the therapeutic INR cohort (p=0.214). The differences in the proportions of thromboembolism, bleeding, or death were not significant between the cohorts (p>0.05). No significant differences were noted in the hazard of thromboembolism, bleeding, or death between the cohorts (p>0.05).
Patients with stable INRs while receiving warfarin who experience a significant subtherapeutic INR value have a low risk of thromboembolism in the ensuing 90 days. The risk was similar to that observed in a matched control population in whom therapeutic anticoagulation was maintained. These findings do not support the practice of anticoagulant bridge therapy for patients stabilized on warfarin therapy to reduce their risk for thromboembolism during isolated periods of subtherapeutic anticoagulation.
量化在接受华法林治疗且先前抗凝稳定的患者中，国际标准化比值（INR）显著低于治疗范围时发生血栓栓塞的绝对风险。
回顾性匹配队列分析。
综合医疗服务体系中的集中抗凝服务。
1998年1月至2005年12月期间共2597例接受华法林治疗的成年患者；1080例患者属于低INR队列，根据首次INR日期、华法林治疗指征和年龄与1517例治疗性INR队列患者进行匹配。
稳定的治疗性抗凝定义为两次INR值（间隔至少2周测量）处于或高于治疗范围。低INR队列包括第三次INR值比其治疗范围低0.5个单位或更多的患者。治疗性INR队列包括有第三次治疗性INR值且在随后90天内没有INR值比其目标INR范围低0.2个单位或更多的患者。主要结局是首次INR后90天内与抗凝相关的血栓栓塞。次要结局是首次INR后90天内首次出现与抗凝相关并发症（出血、血栓栓塞或死亡）的时间。低INR队列发生4例血栓栓塞事件（0.4%），治疗性INR队列发生1例事件（0.1%）（p = 0.214）。队列间血栓栓塞、出血或死亡比例的差异无统计学意义（p>0.05）。队列间血栓栓塞、出血或死亡风险无显著差异（p>0.05）。
接受华法林治疗且INR稳定但出现显著低于治疗范围INR值的患者，在随后90天内发生血栓栓塞的风险较低。该风险与维持治疗性抗凝的匹配对照人群中观察到的风险相似。这些发现不支持对接受华法林治疗已稳定的患者进行抗凝桥接治疗以降低其在抗凝治疗未达标的孤立时间段内发生血栓栓塞风险的做法。
