ImportanceDiltiazem, a commonly prescribed ventricular rate–control medication for patients with atrial fibrillation, inhibits apixaban and rivaroxaban elimination, possibly causing overanticoagulation.ObjectiveTo compare serious bleeding risk for new users of apixaban or rivaroxaban with atrial fibrillation treated with diltiazem or metoprolol.Design, Setting, and ParticipantsThis 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.ExposuresDiltiazem and metoprolol.Main Outcomes and MeasuresThe 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.ResultsThe 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 RelevanceIn 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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使用地尔硫卓联合阿哌沙班或利伐沙班治疗心房颤动患者的严重出血

重要性地尔硫卓是房颤患者常用的心室率控制药物，它会抑制阿哌沙班和利伐沙班的消除，可能导致过度抗凝。目的比较阿哌沙班或利伐沙班新使用者与地尔硫卓或美托洛尔治疗房颤的严重出血风险。设计、设置这项回顾性队列研究包括 65 岁或以上患有心房颤动的医疗保险受益人，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。对患者进行了长达 365 天的随访至 2020 年 11 月 30 日。数据分析时间为 2023 年 8 月至 2024 年 2 月。暴露地尔硫卓和美托洛尔。主要结果和措施主要结果是出血相关的住院治疗和死亡以及近期出血证据的综合结果。次要结局是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）以及近期无出血证据的死亡。风险比 (HR) 和比率差异 (RD) 根据重叠加权的协变量差异进行调整。结果该研究包括 204 155 名美国医疗保险受益人，其中 53 275 人接受地尔硫卓治疗，150 880 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 90 927 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结局风险增加（RD，10.6 [95% CI，7.0-14.2]/1000 PY；HR，1.21 [95% CI，1.13-1.29]）及其与出血相关的住院治疗的组成部分（每 1000 PY RD，8.2 [95% CI，5.1-11.4]；HR，1.22 [95% CI，1.13-1.31]）和近期有出血证据的死亡（RD，每 1000 PY 2.4 [95% CI，0.6-4.2]）与接受美托洛尔治疗的患者相比，1000 PY；HR，1.19 [95% CI，1.05-1.34]）。地尔硫卓初始剂量超过 120 mg/d 的主要结局风险（RD，15.1 [95% CI，10.2-20.1]/1000 PY；HR，1.29 [95% CI，1.19-1.39]）高于较低剂量的主要结局风险。剂量（RD，6.7 [95% CI，2.0-11.4]/1000 PY；HR，1.13 [95% CI，1.04-1.24]）。对于超过 120 mg/d 的剂量，发生重大缺血或出血事件的风险增加（HR，1.14 [95% CI，1.02-1.27]）。两个剂量组的缺血性中风或全身性栓塞或死亡风险均没有显着变化，且近期没有出血证据。当直接比较接受高剂量和低剂量地尔硫卓治疗的患者时，主要结局的 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治疗的房颤 Medicare 患者中，地尔硫卓与严重出血的风险比美托洛尔更大，尤其是地尔硫卓剂量超过 120 mg/d 时。