BACKGROUND:The efficacy and safety of non–vitamin-K antagonist oral anticoagulants (NOACs) across the spectrum of body mass index (BMI) and body weight (BW) remain uncertain.METHODS:We analyzed data from COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation), which pooled patient-level data from the 4 pivotal randomized trials of NOAC versus warfarin in patients with atrial fibrillation. The primary efficacy and safety outcomes were stroke or systemic embolic events (stroke/SEE) and major bleeding, respectively; secondary outcomes were ischemic stroke/SEE, intracranial hemorrhage, death, and the net clinical outcome (stroke/SEE, major bleeding, or death). Each outcome was examined across BMI and BW. Because few patients had a BMI <18.5 kg/m² (n=598), the primary analyses were restricted to those with a BMI ≥18.5 kg/m².RESULTS:Among 58 464 patients, the median BMI was 28.3 (interquartile range, 25.2–32.2) kg/m², and the median BW was 81.0 (interquartile range, 70.0–94.3) kg. The event probability of stroke/SEE was lower at a higher BMI irrespective of treatment, whereas the probability of major bleeding was lower at a higher BMI with warfarin but relatively unchanged across BMI with NOACs. NOACs reduced stroke/SEE overall (adjusted hazard ratio [HR_adj], 0.80 [95% CI, 0.73–0.88]; P<0.001), with a generally consistent effect across BMI (P_trend across HRs, 0.48). NOACs also reduced major bleeding overall (HR_adj, 0.88 [95% CI, 0.82–0.94]; P<0.001), but with attenuation of the benefit at a higher BMI (trend test across BMI [P_trend], 0.003). The overall treatment effects of NOACs versus warfarin for secondary outcomes were consistent across BMI, with the exception of the net clinical outcome and death. While these outcomes were overall reduced with NOACs (net clinical outcome, HR_adj, 0.91 [95% CI, 0.87–0.95]; P<0.001; death, HR_adj, 0.91 [95% CI, 0.86–0.97]; P=0.003), these benefits were attenuated at higher BMI (P_trend, 0.001 and 0.08, respectively). All findings were qualitatively similar when analyzed across BW.CONCLUSIONS:The treatment effect of NOACs versus warfarin in atrial fibrillation is generally consistent for stroke/SEE across the spectrum of BMI and BW, whereas the reduction in major bleeding is attenuated in those with higher BMI or BW. Death and the net clinical outcome are overall reduced with NOACs over warfarin, although there remain uncertainties for these outcomes at a very high BMI and BW.

中文翻译：

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非维生素 K 拮抗剂口服抗凝剂与华法林在体重指数和体重范围内的疗效和安全性：对房颤患者 4 项随机临床试验的个体患者数据荟萃分析

背景：非维生素 K 拮抗剂口服抗凝剂 (NOAC) 在整个体重指数 (BMI) 和体重 (BW) 范围内的有效性和安全性仍不确定。 方法：我们分析了 COMBINE AF（多个组织之间的合作）的数据。更好地研究房颤中非维生素 K 拮抗剂口服抗凝剂使用的机构），该报告汇集了 4 项针对房颤患者使用 NOAC 与华法林的关键随机试验的患者水平数据。主要疗效和安全性结局分别是卒中或全身性栓塞事件（卒中/SEE）和大出血；次要结局是缺血性卒中/SEE、颅内出血、死亡和净临床结局（卒中/SEE、大出血或死亡）。每个结果均通过 BMI 和 BW 进行检查。由于很少有患者 BMI <18.5 kg/m ² (n=598)，因此主要分析仅限于 BMI ≥18.5 kg/m ²的患者。 结果：在 58 464 名患者中，中位 BMI 为 28.3（四分位数间距） ，25.2–32.2）kg/m ²，中位体重为81.0（四分位距，70.0–94.3）kg。无论是否接受治疗，BMI 较高时中风/SEE 的事件概率较低，而使用华法林时 BMI 较高时大出血的概率较低，但使用 NOAC 时 BMI 相对不变。NOAC 总体上减少了中风/SEE（调整后的风险比 [HR _adj ]，0.80 [95% CI，0.73-0.88]；P <0.001），在整个 BMI 范围内具有总体一致的效果（跨 HR 的P_趋势，0.48）。NOAC 还总体上减少了大出血（HR _adj，0.88 [95% CI，0.82-0.94]；P <0.001），但随着 BMI 较高，其益处会减弱（跨 BMI 的趋势检验 [ P_趋势]，0.003）。除净临床结果和死亡外，NOAC 与华法林对次要结局的总体治疗效果在整个 BMI 范围内一致。虽然 NOAC 总体上降低了这些结果（净临床结果，HR _adj，0.91 [95% CI，0.87–0.95]；P <0.001；死亡，HR _adj，0.91 [95% CI，0.86–0.97]；P = 0.003 ），这些益处在 BMI 较高时减弱（P_趋势分别为 0.001 和 0.08）。对 BW 进行分析时，所有结果在质量上都相似。结论：在 BMI 和 BW 范围内，NOAC 与华法林治疗心房颤动的中风/SEE 治疗效果总体一致，而在 BMI 较高的患者中，大出血的减少程度减弱或体重。与华法林相比，NOAC 总体上降低了死亡和净临床结果，尽管在 BMI 和 BW 非常高的情况下，这些结果仍然存在不确定性。