估算房颤人群中维生素 K 拮抗剂抗凝获益：来自 12 项随机试验的竞争风险证据。
Estimating Vitamin K Antagonist Anticoagulation Benefit in People With Atrial Fibrillation Accounting for Competing Risks: Evidence From 12 Randomized Trials.
机构信息
Division of General Internal Medicine, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA (S.J.S., D.E.S.).
Departments of Medicine and Epidemiology and Community Medicine, University of Ottawa, ON, Canada (C.v.W.).
出版信息
Circ Cardiovasc Qual Outcomes. 2024 Apr;17(4):e010269. doi: 10.1161/CIRCOUTCOMES.123.010269. Epub 2024 Mar 25.
BACKGROUND
Patients with atrial fibrillation have a high mortality rate that is only partially attributable to vascular outcomes. The competing risk of death may affect the expected anticoagulant benefit. We determined if competing risks materially affect the guideline-endorsed estimate of anticoagulant benefit.
METHODS
We conducted a secondary analysis of 12 randomized controlled trials that randomized patients with atrial fibrillation to vitamin K antagonists (VKAs) or either placebo or antiplatelets. For each participant, we estimated the absolute risk reduction (ARR) of VKAs to prevent stroke or systemic embolism using 2 methods-first using a guideline-endorsed model (CHADS-VASc) and then again using a competing risk model that uses the same inputs as CHADS-VASc but accounts for the competing risk of death and allows for nonlinear growth in benefit. We compared the absolute and relative differences in estimated benefit and whether the differences varied by life expectancy.
RESULTS
A total of 7933 participants (median age, 73 years, 36% women) had a median life expectancy of 8 years (interquartile range, 6-12), determined by comorbidity-adjusted life tables and 43% were randomized to VKAs. The CHADS-VASc model estimated a larger ARR than the competing risk model (median ARR at 3 years, 6.9% [interquartile range, 4.7%-10.0%] versus 5.2% [interquartile range, 3.5%-7.4%]; <0.001). ARR differences varied by life expectancies: for those with life expectancies in the highest decile, 3-year ARR difference (CHADS-VASc model - competing risk model 3-year risk) was -1.3% (95% CI, -1.3% to -1.2%); for those with life expectancies in the lowest decile, 3-year ARR difference was 4.7% (95% CI, 4.5%-5.0%).
CONCLUSIONS
VKA anticoagulants were exceptionally effective at reducing stroke risk. However, VKA benefits were misestimated with CHADS-VASc, which does not account for the competing risk of death nor decelerating treatment benefit over time. Overestimation was most pronounced when life expectancy was low and when the benefit was estimated over a multiyear horizon.
背景
房颤患者的死亡率很高，而这一死亡率仅部分归因于血管疾病的发生。死亡的竞争风险可能会影响预期的抗凝治疗获益。我们旨在明确竞争风险是否会对指南推荐的抗凝治疗获益估计产生实质性影响。
方法
我们对 12 项随机对照试验进行了二次分析，这些试验将房颤患者随机分配至维生素 K 拮抗剂（VKA）或安慰剂或抗血小板治疗。对于每个参与者，我们使用 2 种方法估计 VKA 预防卒中或全身性栓塞的绝对风险降低（ARR）：首先使用指南推荐的模型（CHADS-VASc），然后再次使用竞争风险模型，该模型使用与 CHADS-VASc 相同的输入，但考虑了死亡的竞争风险，并允许获益呈非线性增长。我们比较了估计获益的绝对和相对差异，以及这些差异是否因预期寿命而异。
结果
共有 7933 名参与者（中位年龄 73 岁，36%为女性）的预期寿命中位数为 8 年（四分位距 6-12 年），通过合并症调整生命表确定，43%被随机分配至 VKA。CHADS-VASc 模型估计的 ARR 大于竞争风险模型（中位 3 年 ARR，6.9%[四分位距 4.7%-10.0%]与 5.2%[四分位距 3.5%-7.4%]；<0.001）。ARR 差异因预期寿命而异：对于预期寿命最高的十分位数，3 年 ARR 差异（CHADS-VASc 模型-竞争风险模型 3 年风险）为-1.3%（95%CI，-1.3%至-1.2%）；对于预期寿命最低的十分位数，3 年 ARR 差异为 4.7%（95%CI，4.5%-5.0%）。
结论
VKA 抗凝剂在降低卒中风险方面非常有效。然而，CHADS-VASc 并未考虑到死亡的竞争风险，也未考虑到治疗获益随时间的减速，因此对 VKA 获益的估计不准确。当预期寿命较低且估计获益超过多年时，高估最为明显。
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