Department of Cardiology, University Heart Center Zurich, Switzerland (J.S.).
Population Health Research Institute, McMaster University and Hamilton Health Sciences, Canada (J.W.E., S.S.A., O.S., S.Y.).
Circulation. 2020 Jul 7;142(1):40-48. doi: 10.1161/CIRCULATIONAHA.120.046048. Epub 2020 May 21.
Rivaroxaban 2.5 mg twice daily plus acetylsalicylic acid (aspirin; ASA) 100 mg reduced the risk of cardiovascular events as compared with ASA monotherapy in the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) but increased the risk of major bleedings. Analysis of net clinical benefit (NCB) is of key clinical relevance and represents an integrated measure of overall patient outcome.
The current prespecified analysis was performed to assess the NCB of adding rivaroxaban 2.5 mg twice daily to ASA monotherapy in patients with chronic vascular disease in the COMPASS study cohort (intention-to-treat study population), with a specific focus on high-risk subgroups. The predefined NCB outcome was the composite of cardiovascular death, stroke, myocardial infarction, fatal bleeding, or symptomatic bleeding into a critical organ.
A lower number of NCB adverse outcomes was observed with rivaroxaban 2.5 mg twice daily plus ASA versus ASA alone (hazard ratio, 0.80 [95% CI, 0.70-0.91], =0.0005), which became increasingly favorable with longer treatment duration. The main drivers of NCB outcomes were "efficacy" events, in particular stroke (0.5%/y versus 0.8%/y; hazard ratio, 0.58 [95% CI, 0.44-0.76], <0.0001) and cardiovascular death (0.9%/y versus 1.2%/y; hazard ratio, 0.78 [95% CI, 0.64-0.96], =0.02), whereas the bleeding components of the NCB, in particular fatal bleeding (0.09%/y versus 0.06%/y; hazard ratio, 1.49 [95% CI 0.67-3.33], =0.32), only represented a minority of NCB events. In selected high-risk subgroups, including patients with polyvascular disease (≥2 vascular beds affected with atherosclerosis), impaired renal function, heart failure, and/or diabetes mellitus, a larger absolute risk reduction for experiencing a NCB event was observed.
Compared with ASA monotherapy, the combination of rivaroxaban 2.5 mg twice daily plus ASA resulted in fewer NCB events primarily by preventing adverse efficacy events, particularly stroke and cardiovascular mortality, whereas severe bleedings were less frequent and with less clinical impact. The NCB was particularly favorable in high-risk subgroups and those with multiple risk characteristics. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01776424.
在 COMPASS 试验（使用抗凝策略的患者心血管结局）中，与阿司匹林（ASA）单药治疗相比，利伐沙班 2.5mg，每日两次加用乙酰水杨酸（ASA；100mg）降低了心血管事件的风险，但增加了大出血的风险。净临床获益（NCB）的分析具有重要的临床相关性，代表了患者整体预后的综合衡量指标。
目前进行了预先设定的分析，以评估 COMPASS 研究队列（意向治疗研究人群）中慢性血管疾病患者中每日两次加用利伐沙班 2.5mg 与 ASA 单药治疗的 NCB，特别关注高危亚组。预先设定的 NCB 结局是心血管死亡、中风、心肌梗死、致死性出血或有症状的重要器官出血。
与 ASA 单药治疗相比，利伐沙班 2.5mg，每日两次加用 ASA 可观察到较少的 NCB 不良结局（风险比，0.80 [95% CI，0.70-0.91]，=0.0005），且随着治疗时间的延长，这种优势更加明显。NCB 结局的主要驱动因素是“疗效”事件，尤其是中风（0.5%/年与 0.8%/年；风险比，0.58 [95% CI，0.44-0.76]，<0.0001）和心血管死亡（0.9%/年与 1.2%/年；风险比，0.78 [95% CI，0.64-0.96]，=0.02），而 NCB 的出血成分，特别是致死性出血（0.09%/年与 0.06%/年；风险比，1.49 [95% CI 0.67-3.33]，=0.32），仅占 NCB 事件的一小部分。在包括多血管疾病（≥2 个血管床受动脉粥样硬化影响）、肾功能受损、心力衰竭和/或糖尿病在内的选定高危亚组中，观察到经历 NCB 事件的绝对风险降低更大。
与 ASA 单药治疗相比，利伐沙班 2.5mg，每日两次加用 ASA 联合治疗可减少 NCB 事件，主要是通过预防不良疗效事件，尤其是中风和心血管死亡率，而严重出血则更少且临床影响较小。NCB 在高危亚组和具有多种风险特征的患者中尤其有利。
