Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, Ohio.
Department of Clinical Applications, The Ohio State University Wexner Medical Center, Columbus, Ohio.
Pharmacotherapy. 2019 Dec;39(12):1157-1166. doi: 10.1002/phar.2335. Epub 2019 Oct 29.
Bivalirudin, a direct thrombin inhibitor, is a treatment option for the management of heparin-induced thrombocytopenia (HIT) and other coagulation disorders. To date, no published studies have identified patients at risk for or the consequence of subtherapeutic bivalirudin therapy.
The primary objective was to identify factors associated with failure to achieve early therapeutic anticoagulation (ETA) with bivalirudin, defined as achievement of two consecutive therapeutic activated partial thromboplastin times (aPTTs) within 24 hours. Secondary objectives included evaluating whether failure to achieve ETA was a risk factor for clinical outcomes of interest including thromboembolism, hemorrhage, and mortality.
PATIENTS/METHODS: This was a retrospective cohort study. Patients between the ages of 18 and 89 years treated with bivalirudin for 24 hours or longer were identified and classified as either achieving or failing to achieve ETA.
Nonadherence to the dosing protocol (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.07-2.71) and creatinine clearance (CrCl) of 60 ml/min or greater (OR 2.99, 95% CI 1.12-7.97) were significantly associated with failure to achieve ETA in univariate analyses. Conversely, increasing age (OR 0.98, 95% CI 0.97-0.99) was significantly associated with achievement of ETA. Failure to achieve ETA was associated with a 4-fold increase in the odds of thromboembolism.
Younger age, normal renal function, and nonadherence to the dosing protocol when targeting therapeutic anticoagulation is associated with increased risk of failure to achieve ETA. This confers an elevated risk of thromboembolism when using bivalirudin for the management of HIT or other coagulation disorders.
比伐卢定是一种直接凝血酶抑制剂，可用于治疗肝素诱导的血小板减少症（HIT）和其他凝血障碍。迄今为止，尚无研究确定存在发生治疗性抗凝失败的风险因素或明确治疗性抗凝失败的后果。
主要目的是确定与比伐卢定无法早期达到治疗性抗凝（ETA）相关的因素，ETA 定义为在 24 小时内连续两次达到治疗性激活部分凝血活酶时间（aPTT）。次要目的包括评估无法达到 ETA 是否是血栓栓塞、出血和死亡等关注的临床结局的风险因素。
患者/方法：这是一项回顾性队列研究。确定了年龄在 18 至 89 岁之间接受比伐卢定治疗 24 小时或更长时间的患者，并将其分为达到或未达到 ETA 的患者。
未遵循剂量方案（比值比 [OR] 1.7，95%置信区间 [CI] 1.07-2.71）和肌酐清除率（CrCl）为 60 ml/min 或更高（OR 2.99，95% CI 1.12-7.97）在单变量分析中与未能达到 ETA 显著相关。相反，年龄增加（OR 0.98，95% CI 0.97-0.99）与达到 ETA 显著相关。未能达到 ETA 与血栓栓塞的几率增加 4 倍相关。
年龄较小、肾功能正常以及在目标达到治疗性抗凝时未遵循剂量方案与治疗性抗凝失败的风险增加相关。在使用比伐卢定治疗 HIT 或其他凝血障碍时，这会增加血栓栓塞的风险。
