Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Hellerup, Denmark.
Department of Public Health, Section of Biostatistics, University of Copenhagen, Copenhagen K, Denmark.
J Intern Med. 2018 Jan;283(1):45-55. doi: 10.1111/joim.12683. Epub 2017 Sep 21.
Comparative data of non-vitamin K antagonist oral anticoagulants (NOAC) are lacking in patients with atrial fibrillation (AF).
We compared effectiveness and safety of standard and reduced dose NOAC in AF patients.
Using Danish nationwide registries, we included all oral anticoagulant-naïve AF patients who initiated NOAC treatment (2012-2016). Outcome-specific and mortality-specific multiple Cox regressions were combined to compute average treatment effects as 1-year standardized differences in stroke and bleeding risks (g-formula).
Amongst 31 522 AF patients, the distribution of NOAC/dose was as follows: dabigatran standard dose (22.4%), dabigatran-reduced dose (14.0%), rivaroxaban standard dose (21.8%), rivaroxaban reduced dose (6.7%), apixaban standard dose (22.9%), and apixaban reduced dose (12.2%). The 1-year standardized absolute risks of stroke/thromboembolism were 1.73-1.98% and 2.51-2.78% with standard and reduced NOAC dose, respectively, without statistically significant differences between NOACs for given dose level. Comparing standard doses, the 1-year standardized absolute risk (95% CI) for major bleeding was for rivaroxaban 2.78% (2.42-3.17%); corresponding absolute risk differences (95% CI) were for dabigatran -0.93% (-1.45% to -0.38%) and apixaban, -0.54% (-0.99% to -0.05%). The results for major bleeding were similar for reduced NOAC dose. The 1-year standardized absolute risk (95% CI) for intracranial bleeding was for standard dose dabigatran 0.19% (0.22-0.50%); corresponding absolute risk differences (95% CI) were for rivaroxaban 0.23% (0.06-0.41%) and apixaban, 0.18% (0.01-0.34%).
Standard and reduced dose NOACs, respectively, showed no significant risk difference for associated stroke/thromboembolism. Rivaroxaban was associated with higher bleeding risk compared with dabigatran and apixaban and dabigatran was associated with lower intracranial bleeding risk compared with rivaroxaban and apixaban.
在房颤（AF）患者中，缺乏非维生素 K 拮抗剂口服抗凝剂（NOAC）的对照数据。
我们比较了房颤患者中标准剂量和降低剂量 NOAC 的有效性和安全性。
使用丹麦全国性登记处，我们纳入了所有开始 NOAC 治疗的口服抗凝剂初治房颤患者（2012-2016 年）。特定结局和死亡率特定的多重 Cox 回归被组合在一起，以计算 1 年中风和出血风险的标准化差异（g 公式）。
在 31522 名房颤患者中，NOAC/剂量的分布如下：达比加群标准剂量（22.4%）、达比加群低剂量（14.0%）、利伐沙班标准剂量（21.8%）、利伐沙班低剂量（6.7%）、阿哌沙班标准剂量（22.9%）和阿哌沙班低剂量（12.2%）。标准剂量和降低剂量 NOAC 的 1 年标准化绝对中风/血栓栓塞风险分别为 1.73%-1.98%和 2.51%-2.78%，不同 NOAC 之间在给定剂量水平下没有统计学意义上的差异。与标准剂量相比，利伐沙班大出血的 1 年标准化绝对风险（95%CI）为 2.78%（2.42%-3.17%）；达比加群对应的绝对风险差异（95%CI）为-0.93%（-1.45%至-0.38%）和阿哌沙班为-0.54%（-0.99%至-0.05%）。降低剂量 NOAC 的大出血结果相似。标准剂量达比加群颅内出血的 1 年标准化绝对风险（95%CI）为 0.19%（0.22%-0.50%）；利伐沙班对应的绝对风险差异（95%CI）为 0.23%（0.06%-0.41%）和阿哌沙班为 0.18%（0.01%-0.34%）。
标准剂量和降低剂量的 NOAC 分别与相关的中风/血栓栓塞风险无显著差异。与达比加群和阿哌沙班相比，利伐沙班出血风险更高，与利伐沙班和阿哌沙班相比，达比加群颅内出血风险更低。
