PDF(Pubmed)
Abstract：
Diltiazem, a commonly prescribed ventricular rate-control medication for patients with atrial fibrillation, inhibits apixaban and rivaroxaban elimination, possibly causing overanticoagulation.
To compare serious bleeding risk for new users of apixaban or rivaroxaban with atrial fibrillation treated with diltiazem or metoprolol.
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.
Diltiazem and metoprolol.
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.
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).
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.
To compare serious bleeding risk for new users of apixaban or rivaroxaban with atrial fibrillation treated with diltiazem or metoprolol.
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.
Diltiazem and metoprolol.
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.
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).
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.
摘要：
■地尔硫卓，房颤患者常用的心室率控制药物，抑制阿哌沙班和利伐沙班的消除，可能导致抗凝过度.
■比较阿哌沙班或利伐沙班的新使用者与地尔硫卓或美托洛尔治疗的房颤的严重出血风险。
这项回顾性队列研究包括年龄在65岁或以上的房颤患者的Medicare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。到2020年11月30日，对患者进行了365天的随访。对2023年8月至2024年2月的数据进行了分析。
■地尔硫和美托洛尔。
■主要结局是出血相关住院和死亡的复合结果，最近有出血证据。次要结果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,颅内或致命的颅外出血，或最近有出血迹象的死亡)，和没有最近出血证据的死亡。危险比（HR）和比率差异（RD）进行了校正，以重叠加权的协变量差异。
■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]年；52.7%为女性）进行了90927人年（PY）的随访（中位数，120[IQR，59-281]天）。接受地尔硫治疗的患者主要结局的风险增加(RD，每1000日元10.6[95%CI，7.0-14.2]；HR，1.21[95%CI，1.13-1.29])及其出血相关住院的组成部分(RD，每1000日元8.2[95%CI，5.1-11.4]；HR，1.22[95%CI，1.13-1.31]）和近期出血证据的死亡（RD，每1000日元2.4[95%CI，0.6-4.2]；HR，1.19[95%CI，1.05-1.34]）与接受美托洛尔的患者相比。初始剂量超过120mg/d的主要结局风险（RD，每1000日元15.1[95%CI，10.2-20.1]；HR，1.29[95%CI，1.19-1.39])大于低剂量(RD，每1000日元6.7[95%CI，2.0-11.4]；HR，1.13[95%CI，1.04-1.24]）。剂量超过120mg/d时，严重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，两个剂量组缺血性卒中或全身性栓塞或死亡的风险均无显著变化。当直接比较接受高剂量和低剂量地尔硫治疗的患者时，主要结局的HR为1.14(95%CI,1.02-1.26).
■在接受阿哌沙班或利伐沙班治疗的房颤患者中，地尔硫与美托洛尔相比，严重出血的风险更大，特别是地尔硫卓剂量超过120毫克/天。
■比较阿哌沙班或利伐沙班的新使用者与地尔硫卓或美托洛尔治疗的房颤的严重出血风险。
这项回顾性队列研究包括年龄在65岁或以上的房颤患者的Medicare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。到2020年11月30日，对患者进行了365天的随访。对2023年8月至2024年2月的数据进行了分析。
■地尔硫和美托洛尔。
■主要结局是出血相关住院和死亡的复合结果，最近有出血证据。次要结果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,颅内或致命的颅外出血，或最近有出血迹象的死亡)，和没有最近出血证据的死亡。危险比（HR）和比率差异（RD）进行了校正，以重叠加权的协变量差异。
■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]年；52.7%为女性）进行了90927人年（PY）的随访（中位数，120[IQR，59-281]天）。接受地尔硫治疗的患者主要结局的风险增加(RD，每1000日元10.6[95%CI，7.0-14.2]；HR，1.21[95%CI，1.13-1.29])及其出血相关住院的组成部分(RD，每1000日元8.2[95%CI，5.1-11.4]；HR，1.22[95%CI，1.13-1.31]）和近期出血证据的死亡（RD，每1000日元2.4[95%CI，0.6-4.2]；HR，1.19[95%CI，1.05-1.34]）与接受美托洛尔的患者相比。初始剂量超过120mg/d的主要结局风险（RD，每1000日元15.1[95%CI，10.2-20.1]；HR，1.29[95%CI，1.19-1.39])大于低剂量(RD，每1000日元6.7[95%CI，2.0-11.4]；HR，1.13[95%CI，1.04-1.24]）。剂量超过120mg/d时，严重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，两个剂量组缺血性卒中或全身性栓塞或死亡的风险均无显著变化。当直接比较接受高剂量和低剂量地尔硫治疗的患者时，主要结局的HR为1.14(95%CI,1.02-1.26).
■在接受阿哌沙班或利伐沙班治疗的房颤患者中，地尔硫与美托洛尔相比，严重出血的风险更大，特别是地尔硫卓剂量超过120毫克/天。
