住院患者达比加群酯的临床应用调查与分析

目的:调查并分析苏州大学附属第一医院(以下称“我院”)达比加群酯的使用现状,为规范其临床应用提供依据。方法:汇总国内外达比加群酯的相关指南和专家共识及建议并结合药品说明书形成其临床应用合理性评价标准(以下简称“标准”),同时回顾性收集2020年度入住我院并使用达比加群酯的患者资料,对其适应证、禁忌证、用法用量、药物相互作用、桥接转换及围手术期使用等情况进行统计分析。结果:共检索到文献978篇,最终纳入11篇形成“标准”。213例使用达比加群的患者中有56例(26.29%)存在用药不合理现象,其中无适应证用药3例(1.41%),禁忌证用药1例(0.47%),用法用量不合理19例(8.92%),桥接转换不合理4例(1.88%),存在不良药物相互作用1例(1.08%),围手术期用药不合理28例(13.15%)。结论:我院住院患者达比加群酯的临床应用与“标准”仍存在一定差距,且不同科室间存在明显的差异,尤以给药频次和围手术期用药不合理最为突出。药师应及时关注达比加群酯及血栓栓塞性疾病相关循证医学证据的更新,同时积极参与全院患者的抗凝药物管理,进一步规范达比加群酯的临床应用。     

达比加群酯药物利用评价标准的建立与回顾性分析

目的:建立达比加群酯药物利用评价标准(drug use evaluation, DUE),为临床合理应用达比加群酯提供参考。方法:以达比加群酯药品说明书为基础,参考相关指南和文献,通过专家咨询法制订达比加群酯药物利用评价标准,并采用回顾性研究方法,对湖北省某大型三甲医院2021年1-6月使用达比加群酯的住院患者用药进行合理性评价,具体包括适应证、用法用量、联合用药、禁忌证、不良反应监测及药物转换等。结果:共纳入501份病例,完全符合评价标准的合理率为91.42%,不合理应用常见于适应证不适宜(2.2%)和用法用量不适宜(2.0%),同时存在30.3%的联合用药的高风险。结论:建立的达比加群酯的DUE具有较强的科学性、实用性和可行性,该院达比加群酯临床应用中尚存在一些问题,应进一步加强干预,促进临床合理用药。     

Evaluation of Dabigatran- and Warfarin-Associated Hemorrhagic Events Using the FDA-Adverse Event Reporting System Database Stratified by Age

Dabigatran and warfarin are oral anticoagulant drugs widely used for the prevention of stroke in patients with atrial fibrillation. The objective of this study was to evaluate the interaction between aging and dabigatran- and warfarin-induced gastrointestinal (GI) and nervous system hemorrhage using data available in the FDA Adverse Event Reporting System (FAERS) database.We analyzed reports of hemorrhagic events in the GI and nervous system recorded in the FAERS database between 2004 and 2014 using an adjusted reporting odds ratio (ROR).We demonstrated that dabigatran-associated GI hemorrhage was significantly increased in patients over the age of 80 years. The RORs of dabigatran increased with increasing age, although aging had little effect on warfarin-associated GI hemorrhage. The ROR for anticoagulant-associated nervous system hemorrhage was not significantly affected by aging, as compared to GI hemorrhage.Our results indicate that the excretion of dabigatran may be affected by aging, as compared to warfarin, likely due to renal function decline. Our results emphasize the need for physicians to closely monitor GI bleeding in aging patients, because it is closely related to renal function deterioration.     

Pharmacology and mechanisms of action of new oral anticoagulants

The new oral anticoagulants are announced as an important therapeutic revolution, particularly after their approval by authorities for stroke prevention in atrial fibrillation. However, the pharmacology of these new drugs is not homogeneous. In this review, we summarize the main pharmacological characteristics of the new direct anti‐Xa and anti‐IIa agents.     

Drug-drug interactions of non-vitamin K oral anticoagulants

Introduction: The approval of non-vitamin K oral anticoagulants (NOACs) as antithrombotic alternatives to vitamin K antagonists (VKAs) has changed clinical practice. However, the efficacy and safety of the four most commonly used NOACs (dabigatran, rivaroxaban, apixaban and edoxaban) might be compromised by co-administration of other medications used for various major comorbidities. Dose adjustment of the NOACs may be needed to avert cases of concomitant medication affecting NOACs absorption, metabolism and coagulation.

Areas covered: This review summarizes the current knowledge regarding drug-drug interactions of NOACs in order to guide health professionals regarding the dose modification required if the NOACs are co-administered with other medication with potential significant interactions. The data were acquired from searches of PubMed and also from the NOAC reports to the European Medicines Agency and Food and Drug Administration Agency.

Expert opinion: Most of the studies in this field have been organized by pharmaceutical companies. Independent research and registries will provide more information in the near future about the drug-drug interactions of NOACs. P-glycoprotein transporter and cytochrome P450 enzyme complexes appear to be the main pathways where the most drug-drug interactions with NOACs occur.     

Reversal of dabigatran by intraosseous or intravenous idarucizumab in a porcine polytrauma model

Background

Idarucizumab is licensed to reverse dabigatran in life-threatening haemorrhage. Establishment of venous access can be challenging, and the intraosseous (IO) route is a potentially life-saving alternative. In this study, we compared the efficacy and safety of IO or intravenous (i.v.) idarucizumab for dabigatran reversal in a porcine polytrauma model.