Shrestha Sulena, Baser Onur, Kwong Winghan Jacqueline
1 STATinMED Research, Plano, TX, USA.
2 Columbia University, New York, NY, USA.
Ann Pharmacother. 2018 Feb;52(2):147-153. doi: 10.1177/1060028017728295. Epub 2017 Aug 31.
Non-vitamin K antagonist direct oral anticoagulants (DOACs) are fixed-dose regimens indicated for stroke prevention in nonvalvular atrial fibrillation (NVAF) patients. Dose adjustment is necessary among patients with renal insufficiency to optimize efficacy and safety.
To assess DOAC dosing appropriateness and its effect on clinical outcomes in NVAF patients.
Adult NVAF patients with ≥1 DOAC pharmacy claim (January 1, 2013, to December 31, 2014), continuous enrollment for ≥12 months post-index DOAC claim, and documented creatinine clearance within 3 months preindex date in the Optum/Humedica SmartFile database were eligible. DOAC dosage was classified as inappropriate or appropriate by level of renal function, age, and body weight per US prescription information. Cox proportional models were used to assess the risks of bleeding and stroke associated with inappropriate DOAC dosage.
Of the 388 eligible patients, 69 (17.8%) were inappropriately dosed, and rivaroxaban had the highest inappropriate dosing rate. Most inappropriately dosed patients were underdosed. Inappropriately dosed patients were more likely to be older, female, and have a body weight of ≤60 kg; they also had higher mean CHADS-VASc and Charlson comorbidity index scores (all P < 0.05). Overtreated patients had a higher risk of bleeding (hazard ratio [HR] = 5.4; P = 0.006) than undertreated patients (HR = 3.1; P = 0.025) relative to appropriately dosed patients. However, no significant difference in stroke risk was observed, most likely because very few stroke events were observed in the study.
Inappropriate dosing occurred among patients with normal and insufficient renal function. The consideration of clinical factors beyond renal function is necessary to reduce bleeding risk associated with DOAC therapy.
非维生素K拮抗剂直接口服抗凝剂（DOACs）为固定剂量方案，适用于非瓣膜性心房颤动（NVAF）患者的卒中预防。肾功能不全患者有必要调整剂量以优化疗效和安全性。
评估NVAF患者中DOAC剂量的合理性及其对临床结局的影响。
纳入Optum/Humedica SmartFile数据库中在2013年1月1日至2014年12月31日期间有≥1次DOAC药房索赔记录、在首次DOAC索赔后连续入组≥12个月且在首次索引日期前3个月内有记录的肌酐清除率的成年NVAF患者。根据美国处方信息，DOAC剂量根据肾功能水平、年龄和体重分类为不适当或适当。采用Cox比例模型评估与不适当DOAC剂量相关的出血和卒中风险。
在388例符合条件的患者中，69例（17.8%）剂量不适当，利伐沙班的不适当给药率最高。大多数剂量不适当的患者剂量不足。剂量不适当的患者更可能年龄较大、为女性且体重≤60 kg；他们的平均CHADS-VASc和Charlson合并症指数评分也更高（均P<0.05）。与剂量适当的患者相比，治疗过度的患者出血风险更高（风险比[HR]=5.4；P=0.006），而治疗不足的患者出血风险也较高（HR=3.1；P=0.025）。然而，未观察到卒中风险有显著差异，很可能是因为研究中观察到的卒中事件极少。
肾功能正常和肾功能不全的患者均存在剂量不适当的情况。有必要考虑肾功能以外的临床因素，以降低与DOAC治疗相关的出血风险。
