Department of Medicine, Division of Cardiology, University of Alberta, Edmonton, Canada.
Canadian VIGOUR Centre, University of Alberta, Edmonton, Canada.
Eur Heart J Qual Care Clin Outcomes. 2022 Mar 2;8(2):195-201. doi: 10.1093/ehjqcco/qcab002.
To determine the concurrent use of P-glycoprotein (P-gp) or Cytochrome (CYP) 3A4 drugs and non-vitamin K antagonist oral anticoagulants (NOACs) among non-valvular AF (NVAF) patients in clinical practice.
Administrative databases identified all adults (≥18 years) with incident or prevalent NVAF who initiated a NOAC in an outpatient or inpatient setting, between July 2012 and March 2019 in Alberta, Canada. Concurrent use was defined as a P-gp or CYP3A4 dispensation in the 100 days prior to and overlapping NOAC dispensation. The P-gp and CYP3A4 drugs were categorized into three groups and drug-drug interactions classified according to the 2018 European Heart Rhythm Association practical guide. Time-varying Cox models calculated the crude hazard ratio (HR) of outcomes at 1-year. A total of 642 255 NOAC dispensations occurred for 36 566 NVAF patients. Of these, 71 643 (11.2%) had a concurrent dispensation of an interacting P-gp or CYP3A4 drug. Overall, the drug-drug interaction was defined as contraindicated in 2.5%, avoid/caution in 2.3%, and for another 6.7% should require a dose adjustment. When all drug-drug interactions were considered, inappropriate NOAC prescribing occurred in 63% (n = 45 080) of dispensations. There was a significantly higher risk of death (HR 1.58, 1.47-1.70) for a drug-drug interaction but not for stroke (P = 0.89) or major bleeding risk (P = 0.13).
The concurrent use of P-gp or CYP3A4 drugs and NOACs was uncommon but important since almost two-thirds of patients with drug-drug interactions had inappropriate NOAC dosing and a higher risk of death. More attention to this issue is needed.
确定非瓣膜性心房颤动（NVAF）患者在临床实践中同时使用 P-糖蛋白（P-gp）或细胞色素（CYP）3A4 药物和非维生素 K 拮抗剂口服抗凝剂（NOACs）的情况。
在加拿大艾伯塔省，通过行政数据库确定了 2012 年 7 月至 2019 年 3 月期间，在门诊或住院环境中首次使用 NOAC 的所有成年（≥18 岁）NVAF 患者。同时使用的定义为在开始使用 NOAC 的前 100 天内和重叠使用期间开具 P-gp 或 CYP3A4 药物。将 P-gp 和 CYP3A4 药物分为三组，并根据 2018 年欧洲心脏病学会节律协会实用指南对药物-药物相互作用进行分类。时间变化的 Cox 模型计算了 1 年时的结果的粗风险比（HR）。共发生 642 255 例 NOAC 处方，涉及 36 566 例 NVAF 患者。其中，71643 例（11.2%）同时开具了相互作用的 P-gp 或 CYP3A4 药物。总的来说，药物-药物相互作用被定义为禁忌 2.5%，避免/谨慎 2.3%，另外 6.7%需要调整剂量。当考虑所有药物-药物相互作用时，63%（n=45080）的处方中存在不适当的 NOAC 给药。药物-药物相互作用的死亡风险显著升高（HR 1.58，1.47-1.70），但卒中风险（P=0.89）或大出血风险（P=0.13）没有差异。
P-gp 或 CYP3A4 药物与 NOAC 同时使用并不常见，但很重要，因为近三分之二的药物-药物相互作用患者存在不适当的 NOAC 剂量和更高的死亡风险。需要更加关注这个问题。
