Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School Boston, MA (D.L.B.).
Population Health Research Institute, McMaster University and Hamilton Health Sciences, Ontario, Canada (J.W.E., S.J.C., S.S.A., J.B., O.S., S.Y.).
Circulation. 2020 Jun 9;141(23):1841-1854. doi: 10.1161/CIRCULATIONAHA.120.046448. Epub 2020 Mar 28.
Patients with established coronary artery disease or peripheral artery disease often have diabetes mellitus. These patients are at high risk of future vascular events.
In a prespecified analysis of the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies), we compared the effects of rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg daily) versus placebo plus aspirin in patients with diabetes mellitus versus without diabetes mellitus in preventing major vascular events. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included all-cause mortality and all major vascular events (cardiovascular death, myocardial infarction, stroke, or major adverse limb events, including amputation). The primary safety end point was a modification of the International Society on Thrombosis and Haemostasis criteria for major bleeding.
There were 10 341 patients with diabetes mellitus and 17 054 without diabetes mellitus in the overall trial. A consistent and similar relative risk reduction was seen for benefit of rivaroxaban plus aspirin (n=9152) versus placebo plus aspirin (n=9126) in patients both with (n=6922) and without (n=11 356) diabetes mellitus for the primary efficacy end point (hazard ratio, 0.74, =0.002; and hazard ratio, 0.77, =0.005, respectively, =0.77) and all-cause mortality (hazard ratio, 0.81, =0.05; and hazard ratio, 0.84, =0.09, respectively; =0.82). However, although the absolute risk reductions appeared numerically larger in patients with versus without diabetes mellitus, both subgroups derived similar benefit (2.3% versus 1.4% for the primary efficacy end point at 3 years, Gail-Simon qualitative <0.0001; 1.9% versus 0.6% for all-cause mortality, =0.02; 2.7% versus 1.7% for major vascular events, <0.0001). Because the bleeding hazards were similar among patients with and without diabetes mellitus, the prespecified net benefit for rivaroxaban appeared particularly favorable in the patients with diabetes mellitus (2.7% versus 1.0%; Gail-Simon qualitative =0.001).
In stable atherosclerosis, the combination of aspirin plus rivaroxaban 2.5 mg twice daily provided a similar relative degree of benefit on coronary, cerebrovascular, and peripheral end points in patients with and without diabetes mellitus. Given their higher baseline risk, the absolute benefits appeared larger in those with diabetes mellitus, including a 3-fold greater reduction in all-cause mortality. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01776424.
患有稳定型冠状动脉疾病或外周动脉疾病的患者通常患有糖尿病。这些患者未来发生血管事件的风险较高。
在 COMPASS 试验（抗凝策略治疗的人群心血管结局研究）的预设分析中，我们比较了利伐沙班（每日两次 2.5 毫克）加阿司匹林（每日 100 毫克）与安慰剂加阿司匹林在预防主要血管事件方面，在患有糖尿病和不患有糖尿病的患者中的作用。主要疗效终点是心血管死亡、心肌梗死或中风的复合终点。次要终点包括全因死亡率和所有主要血管事件（心血管死亡、心肌梗死、中风或主要不良肢体事件，包括截肢）。主要安全性终点是国际血栓与止血学会（International Society on Thrombosis and Haemostasis）大出血标准的改良。
在整个试验中，有 10341 例患有糖尿病和 17054 例无糖尿病的患者。在有（n=6922）和无（n=11356）糖尿病的患者中，利伐沙班加阿司匹林（n=9152）与安慰剂加阿司匹林（n=9126）相比，均观察到对主要疗效终点（风险比 0.74，P=0.002；风险比 0.77，P=0.005）和全因死亡率（风险比 0.81，P=0.05；风险比 0.84，P=0.09）的获益有一致且相似的相对风险降低，P=0.77）。然而，尽管有糖尿病患者的绝对风险降低似乎在数值上更大，但两个亚组均获得了相似的获益（3 年时主要疗效终点的绝对风险降低分别为 2.3%和 1.4%，Gail-Simon 定性检验<0.0001；全因死亡率分别为 1.9%和 0.6%，P=0.02；主要血管事件分别为 2.7%和 1.7%，P<0.0001）。由于有和无糖尿病患者的出血风险相似，利伐沙班的净获益在有糖尿病的患者中尤其有利（2.7%和 1.0%；Gail-Simon 定性检验 P=0.001）。
在稳定型动脉粥样硬化中，阿司匹林加每日两次 2.5 毫克利伐沙班的联合用药在有和无糖尿病的患者中对冠状动脉、脑血管和外周血管终点的获益具有相似的相对程度。鉴于他们的基线风险较高，有糖尿病的患者的绝对获益似乎更大，包括全因死亡率降低了 3 倍。注册：网址：https://www.clinicaltrials.gov；唯一标识符：NCT01776424。
