Predictors of clinically relevant bleeding during extended anticoagulation for cancer-associated venous thromboembolism (API-CAT): a post-hoc analysis of a randomised, non-inferiority trial.

Methods

API-CAT was a randomised, double-blind, non-inferiority trial done in 121 hospitals in 11 countries.

API-CAT是一项在11个国家的121家医院进行的随机、双盲、非劣效试验。

Eligible patients were adults older than 18 years, with active cancer diagnosed histologically (other than basal-cell or squamous-cell carcinoma of the skin, primary brain tumour, or intra-cerebral metastasis) and acute proximal deep-vein thrombosis or pulmonary embolism, 6 months or more of completed anticoagulation, and an Eastern Cooperative Oncology Group performance status of 0-2.

符合条件的患者是年龄超过18岁的成年人，经组织学诊断患有活动性癌症（皮肤基底细胞癌或鳞状细胞癌、原发性脑肿瘤或脑内转移除外），并伴有急性近端深静脉血栓形成或肺栓塞，已完成至少6个月的抗凝治疗，并且东部肿瘤协作组（ECOG）的体能状态评分为0-2分。

Patients were centrally randomly assigned (1:1) to apixaban 5·0 mg or 2·5 mg twice daily orally for 12 months using an interactive web-response system, and stratified by trial centre, index event, and cancer site.

患者通过交互式网络响应系统以1:1的比例随机分配到每日两次口服阿哌沙班5.0毫克或2.5毫克，持续12个月，并根据试验中心、索引事件和癌症部位进行分层。

The primary endpoint, reported previously, was the centrally adjudicated fatal or non-fatal recurrent venous thromboembolism.

先前报告的主要终点是中心评估的致命或非致命性复发性静脉血栓栓塞症。

The primary objective for this post-hoc analysis was to identify predictors of clinically relevant bleeding during extended therapy in the overall population and to evaluate how these predictors vary according to cancer type.

本事后分析的主要目标是在整个患者群体中识别延长治疗期间临床相关出血的预测因素，并评估这些预测因素如何根据癌症类型而变化。

The post hoc-analysis was done in the intention-to-treatpopulation, multivariable competing-risks regression model was built with clinically relevant bleeding as the dependent variable and was adjusted for apixaban dose.

事后分析是在意向治疗人群中进行的，构建了一个多变量竞争风险回归模型，以临床相关的出血作为因变量，并对阿哌沙班剂量进行了调整。

The association between potential predictors and clinically relevant bleeding was expressed as subdistribution hazard ratio(HR) with 95% CIs.

潜在预测因子与临床相关出血之间的关联以亚分布风险比（HR）表示，并附有95%置信区间。

Variables with a p value less than 0·05 were considered statistically significant associated with clinically relevant bleeding.

p 值小于 0.05 的变量被认为与临床相关出血有统计学显著性关联。

The trial is registered with ClinicalTrials.gov (NCT03692065) and is complete.

该试验已在 ClinicalTrials.gov 注册（NCT03692065），并且已经完成。

Results

Between Oct 11, 2018, and Sept 6, 2023, 1766 patients were randomly assigned to the reduced-dose group (n=866) or the full-dose group (n=900).

2018年10月11日至2023年9月6日期间，1766名患者被随机分配到减量组（n=866）或全量组（n=900）。

Median follow-up was 12·9 months (IQR 11·8-13·2). 766 (43·4%) of 1766 patients were male and 1000 (56·6%) were female.

中位随访时间为12.9个月（四分位数间距11.8-13.2）。1766名患者中，766名（43.4%）为男性，1000名（56.6%）为女性。

At 12 months, clinically relevant bleeding occurred in 238 patients.

在12个月时，有238名患者发生了临床上相关的出血事件。

In the overall population, anaemia and/or thrombocytopenia (subdistribution HR 1·93 [95% CI 1·27-2·95]), age 75 years or older (1·51 [1·14-2·02]), pulmonary embolism as the index event (1·47 [1·03-2·10]), and male sex (1·38 [1·05-1·82]) were significantly associated with an increased risk of clinically relevant bleeding.

在整个人群中，贫血和/或血小板减少症（亚分布风险比1.93 [95%置信区间1.27-2.95]）、年龄75岁或以上（1.51 [1.14-2.02]）、以肺栓塞为初始事件（1.47 [1.03-2.10]）以及男性性别（1.38 [1.05-1.82]）与临床上相关出血风险显著增加显著相关。

These results are homogeneous across cancer sites, with no evidence of statistically significant interaction between dose regimen and any predictor (all pinteraction>0·30).

这些结果在不同癌症部位之间是均匀的，没有证据表明剂量方案与任何预测因素之间存在统计学上显著的相互作用（所有pinteraction>0.30）。

interpretation

During extended treatment for cancer-associated VTE, four predictors of clinically relevant bleeding were identified in the overall population, with no evidence of interaction with the dosing regimen.

在癌症相关静脉血栓栓塞症的延长治疗期间，在整个人群中确定了四个临床相关出血的预测因素，没有证据表明与剂量方案存在相互作用。

Although the API-CAT study was not designed to specifically address anticoagulation discontinuation, our findings might help clinicians to more effectively balance the benefits and risks of extended anticoagulant therapy.

尽管API-CAT研究并非专门设计来解决抗凝治疗的中断问题，但我们的发现可能有助于临床医生更有效地平衡长期抗凝治疗的利弊。

funding

None.

无。