Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
Cardiovasc Ther. 2016 Apr;34(2):100-6. doi: 10.1111/1755-5922.12173.
Benefits and/or harms (including costs) of non-vitamin K oral anticoagulants (NOACs) versus warfarin therapy need appreciation in relative and absolute terms.
Accordingly, we derived clinically relevant relative and absolute benefit/harm parameters for NOACs (apixaban, dabigatran, rivaroxaban, edoxaban) compared to warfarin from four clinical trials involving atrial fibrillation (AF) patients. For each trial, we tabulated patient numbers enduring four important outcomes and calculated unadjusted relative risk reduction (RRR) and number needed to treat (NNT)/year values (and 95% confidence intervals) for the NAOC compared to warfarin. These outcomes were as follows: stroke/systemic embolism (primary endpoint), hemorrhagic stroke, major bleeds, and death. We also addressed drug acquisition costs.
Each NOAC was noninferior to warfarin for primary-outcome prevention; RRRs were 12-33% and NNT/year values were 182-481, and all but one indicated statistically significant superiority. All the NOACs yielded statistically significant reductions in hemorrhagic stroke risk; RRRs were 42-74% and NNT/year values were 364-528. Major bleeding risk was comparable in both groups. Apixaban yielded a lower NNT/year for preventing death than for primary-outcome prevention. Compared to warfarin, NOAC acquisition costs were 70- to 140-fold greater.
For the primary outcome, the absolute benefits of NOACs were modest (NNT/year values being large). Reduced hemorrhagic stroke rates with NOACs could be due to superior embolic infarct prevention and fewer consequential hemorrhagic transformations. Among apixaban recipients, the absolute mortality benefit exceeded that for the primary outcome, indicating prevention of additional unrelated deaths. The substantially greater NOAC acquisition costs need viewing against probable greater safety and the avoidance of monitoring bleeding risks.
需要从相对和绝对角度评估非维生素 K 口服抗凝剂（NOAC）与华法林治疗的益处和/或危害（包括成本）。
因此，我们从四项涉及房颤（AF）患者的临床试验中得出了 NOAC（阿哌沙班、达比加群、利伐沙班、依度沙班）与华法林相比的临床相关相对和绝对获益/危害参数。对于每个试验，我们列出了四个重要结局中出现的患者数量，并计算了与华法林相比的未调整相对风险降低（RRR）和每治疗人数（NNT）/年值（及其 95%置信区间）。这些结局如下：中风/全身性栓塞（主要终点）、出血性中风、大出血和死亡。我们还考虑了药物获得成本。
与华法林相比，每种 NOAC 在预防主要结局方面均不劣效；RRR 为 12%-33%，NNT/年值为 182-481，除一个外，其余均显示出统计学上的优越性。所有 NOAC 均显著降低了出血性中风风险；RRR 为 42%-74%，NNT/年值为 364-528。两组大出血风险相当。与预防主要结局相比，阿哌沙班预防死亡的 NNT/年更低。与华法林相比，NOAC 的获取成本高 70-140 倍。
对于主要结局，NOAC 的绝对获益适中（NNT/年值较大）。NOAC 降低出血性中风发生率可能归因于更好的栓塞性梗死预防和较少的继发性出血转化。在阿哌沙班治疗组中，绝对死亡率获益超过了主要结局，表明预防了更多无关的死亡。NOAC 较高的获取成本需要与更高的安全性和避免监测出血风险相权衡。
