Moudallel Souad, Steurbaut Stephane, Cornu Pieter, Dupont Alain
Centre for Pharmaceutical Research, Vrije Universiteit Brussel, Jette, Belgium.
Front Pharmacol. 2018 Oct 30;9:1220. doi: 10.3389/fphar.2018.01220. eCollection 2018.
Appropriate dosing of direct oral anticoagulants (DOACs) is required to avoid under- and overdosing that may precipitate strokes or thromboembolic events and bleedings, respectively. Our objective was to analyze the appropriateness of DOAC dosing according to the summaries of product characteristics (SmPC). Furthermore, determinants for inappropriate prescribing were investigated. Retrospective cohort study of hospitalized patients aged ≥60 years with at least one DOAC intake during hospital stay. Descriptive analyses were used to summarize the characteristics of the study population. Chi-square test was used to evaluate differences between DOACs. Binary logistic regression analysis was performed to assess determinants for inappropriate prescribing. For the 772 included patients, inappropriate dosing occurred in 25.0% of hospitalizations with 23.4, 21.9, and 29.7% for dabigatran, rivaroxaban, and apixaban, respectively ( = 0.084). Underdosing was most prevalent for apixaban (24.5%) compared to dabigatran (14.0%) and rivaroxaban (12.8%), < 0.001. In 67.1% (apixaban), 26.7% (dabigatran), and 51.2% (rivaroxaban) of underdosed DOAC cases according to the SmPC, the dose would be considered appropriate according to the European Heart Rhytm Association (EHRA) guidelines. Overdosing was observed in 4.5% (apixaban), 4.7% (dabigatran), and 7.7% (rivaroxaban) of patients. For all DOACs, our analysis showed an age ≥80 years ( = 0.036), use of apixaban ( = 0.026), DOAC use before hospitalization ( = 0.001), intermediate renal function ( = 0.014), and use of narcotic analgesics ( = 0.019) to be associated with a higher rate of inappropriate prescribing. Undergoing surgery was associated with a lower odds of inappropriate prescribing ( = 0.012). For rivaroxaban, use of medication for hypothyroidism ( = 0.027) and the reduced dose ( < 0.001) were determinants for inappropriate prescribing. Treatment of venous thromboembolism was associated with less errors ( = 0.002). For apixaban, severe renal insufficiency ( < 0.001) and initiation in hospital ( = 0.016) were associated with less and the reduced dose ( < 0.001) with more inappropriate prescribing. No determinants were found in the dabigatran subgroup. Inappropriate DOAC prescribing is frequent with underdosing being the most common drug related problem when using the SmPC as reference. More appropriate prescriptions were found when taking the EHRA guidelines into account. Analysis of determinants of inappropriate prescribing yielded insights in the risk factors associated with inappropriate DOAC prescriptions.
需要给予直接口服抗凝剂（DOACs）适当剂量，以避免分别可能引发中风或血栓栓塞事件及出血的剂量不足和过量情况。我们的目的是根据产品特性摘要（SmPC）分析DOAC给药的适当性。此外，还对不适当处方的决定因素进行了调查。对住院期间年龄≥60岁且至少服用过一次DOAC的患者进行回顾性队列研究。采用描述性分析来总结研究人群的特征。使用卡方检验来评估不同DOAC之间的差异。进行二元逻辑回归分析以评估不适当处方的决定因素。对于纳入的772例患者，25.0%的住院治疗存在剂量不当情况，达比加群、利伐沙班和阿哌沙班分别为23.4%、21.9%和29.7%（P = 0.084）。与达比加群（14.0%）和利伐沙班（12.8%）相比，阿哌沙班的剂量不足最为普遍（24.5%），P < 0.001。根据SmPC，在67.1%（阿哌沙班）、26.7%（达比加群）和51.2%（利伐沙班）的剂量不足DOAC病例中，根据欧洲心律协会（EHRA）指南，该剂量将被视为适当。4.5%（阿哌沙班）、4.7%（达比加群）和7.7%（利伐沙班）的患者出现剂量过量。对于所有DOAC，我们的分析显示年龄≥80岁（P = 0.036）、使用阿哌沙班（P = 0.026）、住院前使用DOAC（P = 0.001）、中度肾功能（P = 0.014）以及使用麻醉性镇痛药（P = 0.019）与更高的不适当处方率相关。接受手术与较低的不适当处方几率相关（P = 0.012）。对于利伐沙班，使用治疗甲状腺功能减退的药物（P = 0.027）和剂量降低（P < 0.001）是不适当处方的决定因素。静脉血栓栓塞的治疗与较少的错误相关（P = 0.002）。对于阿哌沙班，严重肾功能不全（P < 0.001）和住院时开始用药（P = 0.016）与较少的不适当处方相关，而剂量降低（P < 0.001）与更多的不适当处方相关。在达比加群亚组中未发现决定因素。以SmPC为参考时，不适当的DOAC处方很常见，剂量不足是最常见的药物相关问题。考虑EHRA指南时发现了更适当的处方。对不适当处方决定因素的分析揭示了与不适当DOAC处方相关的风险因素。
