Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Cardio-Oncology Program, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
JAMA Netw Open. 2021 Feb 1;4(2):e2036304. doi: 10.1001/jamanetworkopen.2020.36304.
It is unclear whether the clinical benefits associated with non-vitamin K antagonist oral anticoagulants (NOACs) are similar to those associated with low-molecular-weight heparins (LMWHs) in Asian individuals with cancer and acute venous thromboembolism (VTE).
To compare the risk of recurrent thromboembolic events and bleeding associated with use of a NOAC vs use of the LMWH enoxaparin in Asian individuals with cancer-associated VTE.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted using data from the Chang Gung Research Database, a multi-institutional electronic medical records database in Taiwan. A cohort of 1109 patients with cancer-associated VTE were identified between January 1, 2012, and January 31, 2019. Data were analyzed from March 2019 through December 2020.
Receiving a NOAC (including rivaroxaban, apixaban, edoxaban, or dabigatran) or the LMWH enoxaparin.
The primary outcomes were composite recurrent VTE or major bleeding. Stabilized inverse probability of treatment weighting was used to balance baseline covariates. We compared risks of recurrent VTE or major bleeding between groups using Cox proportional hazards models. In addition, we conducted an analysis using a Fine and Gray subdistribution hazard model that considered death as a competing risk.
Among 1109 patients with cancer and newly diagnosed VTE, 578 (52.1%) were women and the mean (SD) age at index date was 66.0 (13.0) years; 529 patients (47.7%) received NOACs and 580 patients (52.3%) received the LMWH enoxaparin. Composite recurrent VTE or major bleeding occurred in 75 patients (14.1%) in the NOAC group and 101 patients (17.4%) in the enoxaparin group (weighted hazard ratio [HR], 0.77; 95% CI, 0.56-1.07; P = .11). The groups had similar risk of VTE recurrence (HR, 0.62; 95% CI, 0.39-1.01; P = .05) and major bleeding (HR, 0.80; 95% CI, 0.52-1.24; P = .32) at 12 months of follow-up. However, taking a NOAC was associated with a significantly lower risk of gastrointestinal bleeding compared with receiving enoxaparin (10 patients [1.9%] vs 41 patients [7.1%]; HR, 0.29; 95% CI, 0.15-0.59; P < .001). Findings for both primary outcomes were consistent with competing risk analyses (recurrent VTE: HR, 0.68; 95% CI, 0.45-1.01; P = .05; major bleeding: HR, 0.77; 95% CI, 0.51-1.16; P = .21).
This cohort study found that in real-world practice, among Asian patients with cancer-associated VTE, use of a NOAC was associated with a similar risk for recurrent VTE or major bleeding compared with use of the LMWH enoxaparin. Nonetheless, use of a NOAC was associated with a significantly lower rate of gastrointestinal bleeding. Further prospective studies are needed to confirm these findings.
重要性:尚不清楚与新型口服抗凝剂(NOAC)相关的临床益处是否与亚洲癌症合并急性静脉血栓栓塞症(VTE)患者相关的低分子量肝素(LMWH)相似。
目的:比较在亚洲癌症合并 VTE 患者中使用 NOAC 与使用 LMWH 依诺肝素相关的复发性血栓栓塞事件和出血风险。
设计、设置和参与者:本队列研究使用来自台湾多机构电子病历数据库的长庚研究数据库的数据进行。2012 年 1 月 1 日至 2019 年 1 月 31 日期间确定了 1109 例癌症合并 VTE 患者的队列。2019 年 3 月至 2020 年 12 月进行数据分析。
暴露:接受新型口服抗凝剂(包括利伐沙班、阿哌沙班、依度沙班或达比加群)或 LMWH 依诺肝素。
主要结局和措施:主要结局是复合复发性 VTE 或主要出血。使用稳定的逆概率治疗加权来平衡基线协变量。我们使用 Cox 比例风险模型比较两组之间复发性 VTE 或主要出血的风险。此外,我们使用 Fine 和 Gray 亚分布风险模型进行了分析,该模型将死亡视为竞争风险。
结果:在 1109 例患有癌症和新诊断 VTE 的患者中,578 例(52.1%)为女性,索引日期的平均(SD)年龄为 66.0(13.0)岁;529 例(47.7%)患者接受了 NOAC,580 例(52.3%)患者接受了 LMWH 依诺肝素。75 例(14.1%)NOAC 组和 101 例(17.4%)依诺肝素组发生复合复发性 VTE 或主要出血(加权风险比[HR],0.77;95%CI,0.56-1.07;P=0.11)。两组在 12 个月的随访中具有相似的 VTE 复发风险(HR,0.62;95%CI,0.39-1.01;P=0.05)和主要出血风险(HR,0.80;95%CI,0.52-1.24;P=0.32)。然而,与接受依诺肝素相比,使用 NOAC 与胃肠道出血风险显著降低相关(10 例[1.9%]与 41 例[7.1%];HR,0.29;95%CI,0.15-0.59;P<0.001)。两种主要结局的发现与竞争风险分析一致(复发性 VTE:HR,0.68;95%CI,0.45-1.01;P=0.05;主要出血:HR,0.77;95%CI,0.51-1.16;P=0.21)。
结论和相关性:本队列研究发现,在亚洲癌症合并 VTE 患者的实际治疗中,与使用 LMWH 依诺肝素相比,使用新型口服抗凝剂与复发性 VTE 或主要出血的风险相似。尽管如此,使用新型口服抗凝剂与胃肠道出血的发生率显著降低相关。需要进一步的前瞻性研究来证实这些发现。