Division of Cardiovascular Diseases, Section of Heart Failure and Transplant, University of Iowa College of Medicine, Iowa City, IA, USA.
Division of Cardiovascular Medicine, 200 Hawkins Dr, Iowa City, IA, 52242, USA.
BMC Cardiovasc Disord. 2020 Feb 3;20(1):42. doi: 10.1186/s12872-020-01340-4.
We evaluated adherence to dosing criteria for patients with atrial fibrillation (AF) taking dabigatran or rivaroxaban and the impact of off-label dosing on thromboembolic and bleeding risk.
We used data for a retrospective cohort from a large U.S. health plan for Medicare beneficiaries age > =65 years with AF who initiated dabigatran or rivaroxaban during 2010-2016. Stroke and major bleeding were quantified in patients who were eligible for low dose but received standard dose, and in patients who were eligible for standard dose but received low dose.
We identified 8035 and 19,712 patients who initiated dabigatran or rivaroxaban, respectively. Overall, 1401 (17.4%) and 7820 (39.7%) patients who received dabigatran and rivaroxaban met criteria for low dose, respectively. Of those, 959 (68.5%) and 3904 (49.9%) received standard dose. In contrast, 1013 (15.3%) and 2551 (21.5%) of patients eligible for standard dose dabigatran and rivaroxaban received low dose. Mean follow-up for patients eligible for low and standard dose dabigatran and rivaroxaban were 13.9, 15.1, 10.1, and 12.3 months, respectively. In unadjusted analyses, patients eligible for low or standard dose dabigatran and rivaroxaban but receiving off-label dose, had no differences in the rates of ischemic stroke. Among patients who met criteria for standard dose direct oral anticoagulants (DOAC), use of low dose was associated with significantly higher risk of any major bleeding (Dabigatran: HR = 1.44; 95% CI 1.14-1.8, P = 0.002, Rivaroxaban HR 1.34, 95% CI 1.11-1.6, P = 0.002) and gastrointestinal bleeding (Dabigatran: HR = 1.48; 95% CI 1.08-2, P = 0.016). In patients who met criteria for low dose DOACs, there was lower risk of major bleeding (Dabigatran: HR = 0.59; 95% CI 0.43-0.8, P < 0.001), gastrointestinal (Rivaroxaban: HR 0.79; 95% CI 0.64-0.98, P = 0.03) and intracranial bleeding (Dabigatran: HR = 0.33; 95% CI 0.12-0.9, P = 0.001) with standard dosing. After propensity matching, use of off-label doses was not associated with stroke, major, gastrointestinal or intracranial bleeding for either dabigatran or rivaroxaban.
While a significant number of patients receive higher or lower dose of dabigatran and rivaroxaban than recommended, we found no evidence of significant impact on thromboembolic or hemorrhagic outcomes.
我们评估了服用达比加群或利伐沙班的房颤（AF）患者的剂量标准依从性，以及标签外剂量与血栓栓塞和出血风险的关系。
我们使用了来自美国大型医疗保险计划的 65 岁以上房颤患者的回顾性队列数据，这些患者在 2010-2016 年期间开始使用达比加群或利伐沙班。在符合低剂量但接受标准剂量的患者和符合标准剂量但接受低剂量的患者中，量化了卒中（中风）和大出血的发生率。
我们分别确定了 8035 名和 19712 名开始使用达比加群或利伐沙班的患者。总体而言，分别有 1401（17.4%）和 7820（39.7%）名接受达比加群和利伐沙班的患者符合低剂量标准。其中，分别有 959（68.5%）和 3904（49.9%）名患者接受了标准剂量。相比之下，1013（15.3%）和 2551（21.5%）名符合达比加群和利伐沙班标准剂量的患者接受了低剂量。符合低剂量和标准剂量达比加群和利伐沙班的患者的平均随访时间分别为 13.9、15.1、10.1 和 12.3 个月。在未调整的分析中，符合达比加群和利伐沙班低或标准剂量标准但接受标签外剂量的患者，其缺血性卒中发生率无差异。在符合标准剂量直接口服抗凝剂（DOAC）标准的患者中，使用低剂量与任何主要出血（达比加群：HR=1.44；95%CI 1.14-1.8，P=0.002；利伐沙班 HR 1.34，95%CI 1.11-1.6，P=0.002）和胃肠道出血（达比加群：HR=1.48；95%CI 1.08-2，P=0.016）的风险显著增加。在符合低剂量 DOAC 标准的患者中，大出血（达比加群：HR=0.59；95%CI 0.43-0.8，P<0.001）、胃肠道（利伐沙班：HR 0.79；95%CI 0.64-0.98，P=0.03）和颅内出血（达比加群：HR=0.33；95%CI 0.12-0.9，P=0.001）的风险较低，接受标准剂量治疗。经过倾向评分匹配后，达比加群或利伐沙班的标签外剂量使用与卒中、大出血、胃肠道出血或颅内出血均无显著相关性。
尽管相当数量的患者服用的达比加群和利伐沙班剂量高于或低于推荐剂量，但我们没有发现这对血栓栓塞或出血结果有重大影响的证据。
