Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
JAMA Neurol. 2020 Jan 1;77(1):43-48. doi: 10.1001/jamaneurol.2019.2984.
The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) randomized clinical trial was stopped early owing to the efficacy of low-dose rivaroxaban plus aspirin in preventing major cardiovascular events. The main reason for early trial termination was the effect of combination therapy on reducing ischemic strokes.
To analyze the association between low-dose rivaroxaban with or without aspirin and different ischemic stroke subtypes.
DESIGN, SETTING, AND PARTICIPANTS: This is a secondary analysis of a multicenter, double-blind, randomized, placebo-controlled study that was performed in 33 countries from March 12, 2013, to May 10, 2016. Patients with stable atherosclerotic vascular disease were eligible, and a total of 27 395 participants were randomized and followed up to February 6, 2017. All first ischemic strokes and uncertain strokes that occurred by this date were adjudicated using TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria. The analysis of ischemic stroke subtypes was evaluated using an intention-to-treat principle. Statistical analysis was performed from March 12, 2013, to February 6, 2017.
Participants received rivaroxaban (2.5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban (5 mg twice a day), or aspirin (100 mg once a day).
Risk of ischemic stroke subtypes during follow-up.
A total of 291 patients (66 women; mean [SD] age, 69.4 [8.5] years; 43 [14.8%] had a previous nonlacunar stroke) experienced an ischemic stroke. During the study, 49 patients (16.8%) received a diagnosis of atrial fibrillation. Applying TOAST criteria, 59 strokes (20.3%) were cardioembolic, 54 strokes (18.6%) were secondary to greater than 50% stenosis of the ipsilateral internal carotid artery, 42 strokes (14.4%) had a negative evaluation that met criteria for embolic stroke of undetermined source, and 21 strokes (7.2%) were secondary to small vessel disease. There were significantly fewer cardioembolic strokes (hazard ratio [HR], 0.40 [95% CI, 0.20-0.78]; P = .005) and embolic strokes of undetermined source (HR, 0.30 [95% CI, 0.12-0.74]; P = .006) in the combination therapy group compared with the aspirin-only group. A trend for reduction in strokes secondary to small vessel disease (HR, 0.36 [95% CI, 0.12-1.14]; P = .07) was not statistically significant. No significant difference was observed between the 2 groups in strokes secondary to greater than 50% carotid artery stenosis (HR, 0.85 [95% CI, 0.45-1.60]; P = .61). Rivaroxaban, 5 mg, twice daily showed a trend for reducing cardioembolic strokes compared with aspirin (HR, 0.57 [95% CI, 0.31-1.03]; P = .06) but was not associated with reducing other stroke subtypes.
For patients with systemic atherosclerosis, low-dose rivaroxaban plus aspirin was associated with large, significant reductions in cardioembolic strokes and embolic strokes of undetermined source. However, these results of exploratory analysis need to be independently confirmed before influencing clinical practice.
ClinicalTrials.gov identifier: NCT01776424.
COMPASS（使用抗凝策略的人群心血管结果）随机临床试验因低剂量利伐沙班加阿司匹林预防主要心血管事件的疗效而提前终止。提前终止试验的主要原因是联合治疗对减少缺血性中风的影响。
分析低剂量利伐沙班联合或不联合阿司匹林与不同缺血性中风亚型的关系。
设计、地点和参与者：这是一项多中心、双盲、随机、安慰剂对照研究的二次分析，于 2013 年 3 月 12 日至 2016 年 5 月 10 日在 33 个国家进行。符合稳定动脉粥样硬化性血管疾病条件的患者有资格参加，共有 27395 名患者被随机分组并随访至 2017 年 2 月 6 日。所有在此日期前发生的首次缺血性中风和不确定的中风均采用 TOAST（急性中风治疗中的 Org 10172 试验）标准进行裁决。使用意向治疗原则评估缺血性中风亚型的分析。统计分析于 2013 年 3 月 12 日至 2017 年 2 月 6 日进行。
参与者接受利伐沙班（每天两次 2.5 毫克）加阿司匹林（每天一次 100 毫克）、利伐沙班（每天两次 5 毫克）或阿司匹林（每天一次 100 毫克）。
随访期间发生的缺血性中风亚型的风险。
共有 291 名患者（66 名女性；平均[SD]年龄 69.4[8.5]岁；43 名[14.8%]有既往腔隙性脑梗死）发生缺血性中风。研究期间，49 名患者（16.8%）被诊断为心房颤动。根据 TOAST 标准，59 例中风（20.3%）为心源性栓塞，54 例中风（18.6%）为同侧颈内动脉大于 50%狭窄所致，42 例中风（14.4%）评估为符合不明来源栓塞性中风标准，21 例中风（7.2%）为小血管疾病所致。与阿司匹林单药组相比，联合治疗组心源性栓塞性中风（HR，0.40[95%CI，0.20-0.78]；P = .005）和不明来源栓塞性中风（HR，0.30[95%CI，0.12-0.74]；P = .006）明显减少。小血管疾病所致中风（HR，0.36[95%CI，0.12-1.14]；P = .07）减少的趋势不具有统计学意义。两组间大于 50%颈动脉狭窄所致中风（HR，0.85[95%CI，0.45-1.60]；P = .61）无显著差异。与阿司匹林相比，利伐沙班 5 毫克，每日两次，降低心源性栓塞性中风的趋势（HR，0.57[95%CI，0.31-1.03]；P = .06），但与降低其他中风亚型无关。
对于患有系统性动脉粥样硬化的患者，低剂量利伐沙班加阿司匹林与心源性栓塞性中风和不明来源栓塞性中风的显著减少显著相关。然而，这些探索性分析的结果需要在独立验证后才能对临床实践产生影响。
ClinicalTrials.gov 标识符：NCT01776424。
