Withdrawal of aspirin in patients with left ventricular assist device treated with vitamin K antagonists: impact of anticoagulation quality in the randomized ARIES-HM3 trial.

Use of vitamin K antagonists (VKA) is mandated to reduce the risk of thrombotic events, but there is heterogeneity in management.

使用维生素K拮抗剂（VKA）是减少血栓事件风险的必要措施，但在管理上存在异质性。

Time in therapeutic range (TTR) is a crucial metric for assessing the quality of VKA management.

治疗范围内的时长（TTR）是评估维生素K拮抗剂（VKA）管理质量的一个关键指标。

The ARIES-HM3 trial demonstrated that aspirin can be safely omitted from the antithrombotic regimen, resulting in reduced bleeding without increased thrombosis.

ARIES-HM3试验表明，可以安全地从抗血栓方案中省略阿司匹林，从而减少出血而不增加血栓形成。

This pre-specified trial analysis explores the relationship of quality of VKA management assessed by TTR with haemocompatibility-related outcomes.

本次预先设定的试验分析探讨了通过时间在治疗范围内（TTR）评估的维生素K拮抗剂（VKA）管理质量与血液相容性相关结果之间的关系。

Methods

ARIES-HM3 was an international, randomized, double-blind, placebo-controlledstudy of aspirin (100 mg/day) or placebo (1:1) with VKA therapy in patients with de-novo HM3 placement.

ARIES-HM3是一项国际性的随机、双盲、安慰剂对照研究，研究对象为接受新型HM3装置植入的患者，比较阿司匹林（每日100毫克）或安慰剂（1:1）与维生素K拮抗剂（VKA）治疗的疗效。

Participants were stratified into low TTR or high TTR groups based on median levels (n = 554).

参与者根据中位数水平被分为低TTR组或高TTR组（n = 554）。

Primary endpoint success and secondary endpoint rates were stratified based on TTR groups.

主要终点的成功率和次要终点的比率根据TTR组进行了分层。

Bleeding rates at 12 months were estimated using an Andersen-Gill model with TTR as a single continuous variable, and multivariable regression analysis was performed.

使用 Andersen-Gill 模型估计了 12 个月内的出血率，其中 TTR 作为单一连续变量，并进行了多变量回归分析。

Results

The percentage of patients with a TTR above or below the median of 56 was similar between the aspirin and placebo groups.

在阿司匹林组和安慰剂组之间，TTR 高于或低于中位数 56 的患者百分比相似。

More participants achieved primary endpoint success with TTR ≥56% (77% vs 66.9%, P = .01).

更多的参与者在TTR≥56%时达到了主要终点的成功（77%对比66.9%，P=0.01）。

Higher TTR was associated with lower bleeding rates at 12 months (26.4 vs 49.2 events per 100 participant-years; rate ratio 1.84, 95% confidence interval[CI] 1.37-2.53) without stroke increase (3.2 vs 2.8 events per 100 participant-years; rate ratio 0.88 [95% CI: 0.30-2.53]).

更高的TTR与12个月时较低的出血率相关（每100参与者年26.4对比49.2事件；比率比1.84，95%置信区间[CI] 1.37-2.53），且没有增加中风率（每100参与者年3.2对比2.8事件；比率比0.88 [95% CI: 0.30-2.53]）。

No interaction was observed between the assigned treatment group and TTR.

未观察到指定治疗组与TTR之间存在相互作用。

Modelling demonstrated a constant decrease in bleeding as a function of increasing TTR.

模型显示，随着TTR的增加，出血呈恒定减少。

Female sex and Black race were independent predictors of low TTR (odds ratio: 1.70 [95% CI: 1.12-2.57]; 1.62 [95% CI: 1.11-2.35], respectively), with more frequent INRs below the therapeutic range.

女性和黑人种族是低TTR（目标治疗比）的独立预测因素（女性的比值比为1.70 [95% 置信区间: 1.12-2.57]；黑人的比值比为1.62 [95% 置信区间: 1.11-2.35]），且INRs（国际标准化比率）低于治疗范围的情况更为频繁。

Multivariable modelling identified age ≥65 years, aspirin use, TTR <56%, and blood urea nitrogen ≥30 mg/dL as predictors of non-surgical bleeding.

多变量建模确定了年龄≥65岁、阿司匹林使用、TTR<56%和血尿素氮≥30 mg/dL作为非手术出血的预测因素。

Conclusions

The quality of VKA management as measured by TTR correlates with the occurrence of non-surgical bleeding in patients with the HM3 LVAD, with a lower TTR associated with an increased bleeding risk.

通过TTR（时间在治疗范围内）测量的VKA（维生素K拮抗剂）管理质量与HM3 LVAD（左心室辅助装置）患者非手术出血的发生相关，较低的TTR与出血风险增加相关。

These data provide new clinical direction to define a benchmark TTR to achieve further mitigation of residual risk of bleeding and enhance haemocompatibility with the HM3 LVAD.

这些数据为定义一个基准TTR提供了新的临床方向，以进一步减轻残余出血风险并提高与HM3 LVAD的血液相容性。