本文由小咖机器人翻译整理

期刊来源：JAMA

原文链接：https://doi.org/10.1001/jama.2024.3867

摘要内容如下：

重要性

地尔硫卓（Diltiazem）是房颤患者常用的心室率控制药物，可抑制阿哌沙班和利伐沙班的消除，可能导致抗凝过度。

目的

比较阿哌沙班或利伐沙班新使用者与接受地尔硫卓或美托洛尔治疗的房颤患者的严重出血风险。

设计、设置和参与者

这项回顾性队列研究纳入了65岁或以上的房颤医疗保险受益人，他们在2012年1月1日至2020年11月29日期间开始使用阿哌沙班或利伐沙班，并开始使用地尔硫卓或美托洛尔治疗。对患者进行了365天的随访，直至2020年11月30日。对2023年8月至2024年2月的数据进行了分析。

曝光

地尔硫卓和美托洛尔。

主要成果和措施

主要转归是出血相关住院和死亡的复合转归，近期有出血证据。次要转归为缺血性卒中或全身性栓塞、主要缺血性或出血性事件（缺血性卒中、全身性栓塞、颅内或致命性颅外出血或近期有出血证据的死亡）和无近期出血证据的死亡。风险比（HR）和比率差异（RDS）通过重叠加权对协变量差异进行调整。

结果

该研究包括204155名美国医疗保险受益人，其中53275人接受地尔硫卓治疗，150880人接受美托洛尔治疗。研究患者（平均[SD]年龄，76.9[7.0]岁；52.7%为女性）进行了90927人年（PY）的随访（中位数，120[IQR，59-281]天）。接受地尔硫卓治疗的患者主要转归的风险增加（RD，10.6[95%CI，7.0-14.2]/1000 PY；HR，1.21[95%CI，1.13-1.29]）及其出血相关住院构成（RD，8.2[95%CI，5.1-11.4]/1000 PY；HR，1.22[95%CI，1.13-1.31]）和近期出血死亡（RD，2.4[95%CI，0.6-4.2]/1000 PY；HR，1.19[95%CI，1.05-1.34]）与接受美托洛尔治疗的患者相比。地尔硫卓初始剂量超过120 mg/d的主要转归风险（RD，15.1[95%CI，10.2-20.1]/1000 PY；HR，1.29[95%CI，1.19-1.39]）大于低剂量组（RD，6.7[95%CI，2.0-11.4]/1000 PY；HR，1.13[95%CI，1.04-1.24]）。剂量超过120 mg/d时，主要缺血或出血事件的风险增加（HR，1.14[95%CI，1.02-1.27]）。在没有近期出血证据的情况下，两个剂量组的缺血性卒中或全身性栓塞或死亡的风险均无显著变化。直接比较接受高剂量和低剂量地尔硫卓治疗的患者时，主要转归的HR为1.14（95%CI，1.02-1.26）。

结论和相关性

在接受阿哌沙班或利伐沙班的Medicare房颤患者中，地尔硫卓比美托洛尔具有更大的严重出血风险，尤其是地尔硫卓剂量超过120 mg/d时。

英文原文如下：

Abstracts

Importance  Diltiazem, a commonly prescribed ventricular rate-control medication for patients with atrial fibrillation, inhibits apixaban and rivaroxaban elimination, possibly causing overanticoagulation.

Objective  To compare serious bleeding risk for new users of apixaban or rivaroxaban with atrial fibrillation treated with diltiazem or metoprolol.

Design, Setting, and Participants  This retrospective cohort study included Medicare beneficiaries aged 65 years or older with atrial fibrillation who initiated apixaban or rivaroxaban use and also began treatment with diltiazem or metoprolol between January 1, 2012, and November 29, 2020. Patients were followed up to 365 days through November 30, 2020. Data were analyzed from August 2023 to February 2024.

Exposures  Diltiazem and metoprolol.

Main Outcomes and Measures  The primary outcome was a composite of bleeding-related hospitalization and death with recent evidence of bleeding. Secondary outcomes were ischemic stroke or systemic embolism, major ischemic or hemorrhagic events (ischemic stroke, systemic embolism, intracranial or fatal extracranial bleeding, or death with recent evidence of bleeding), and death without recent evidence of bleeding. Hazard ratios (HRs) and rate differences (RDs) were adjusted for covariate differences with overlap weighting.

Results  The study included 204 155 US Medicare beneficiaries, of whom 53 275 received diltiazem and 150 880 received metoprolol. Study patients (mean [SD] age, 76.9 [7.0] years; 52.7% female) had 90 927 person-years (PY) of follow-up (median, 120 [IQR, 59-281] days). Patients receiving diltiazem treatment had increased risk for the primary outcome (RD, 10.6 [95% CI, 7.0-14.2] per 1000 PY; HR, 1.21 [95% CI, 1.13-1.29]) and its components of bleeding-related hospitalization (RD, 8.2 [95% CI, 5.1-11.4] per 1000 PY; HR, 1.22 [95% CI, 1.13-1.31]) and death with recent evidence of bleeding (RD, 2.4 [95% CI, 0.6-4.2] per 1000 PY; HR, 1.19 [95% CI, 1.05-1.34]) compared with patients receiving metoprolol. Risk for the primary outcome with initial diltiazem doses exceeding 120 mg/d (RD, 15.1 [95% CI, 10.2-20.1] per 1000 PY; HR, 1.29 [95% CI, 1.19-1.39]) was greater than that for lower doses (RD, 6.7 [95% CI, 2.0-11.4] per 1000 PY; HR, 1.13 [95% CI, 1.04-1.24]). For doses exceeding 120 mg/d, the risk of major ischemic or hemorrhagic events was increased (HR, 1.14 [95% CI, 1.02-1.27]). Neither dose group had significant changes in the risk for ischemic stroke or systemic embolism or death without recent evidence of bleeding. When patients receiving high- and low-dose diltiazem treatment were directly compared, the HR for the primary outcome was 1.14 (95% CI, 1.02-1.26).

Conclusions and Relevance  In Medicare patients with atrial fibrillation receiving apixaban or rivaroxaban, diltiazem was associated with greater risk of serious bleeding than metoprolol, particularly for diltiazem doses exceeding 120 mg/d.

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