Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada (K.R.B., R.C.W.).
Population Heath Research Institute, McMaster University and Hamilton Health Sciences, ON, Canada (S.J.C., T.M., J.B., S.Y., J.W.E.).
Circulation. 2020 Apr 7;141(14):1141-1151. doi: 10.1161/CIRCULATIONAHA.119.044598. Epub 2020 Mar 17.
The COMPASS trial (Cardiovascular Outcomes for People using Anticoagulation Strategies) demonstrated that dual pathway inhibition (DPI) with rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily versus aspirin 100 mg once daily reduced the primary major adverse cardiovascular event (MACE) outcome of cardiovascular death, myocardial infarction, or stroke, as well as, mortality, in patients with chronic coronary syndromes or peripheral arterial disease. Whether this remains true in patients with a history of percutaneous coronary intervention (PCI) is unknown.
In a prespecified subgroup analysis from COMPASS, we examined the outcomes of patients with chronic coronary syndrome with or without a previous PCI treated with DPI versus aspirin alone. Among patients with a previous PCI, we studied the effects of treatment according to the timing of the previous PCI.
Of the 27 395 patients in COMPASS, 16 560 patients with a chronic coronary syndrome were randomly assigned to DPI or aspirin, and, of these, 9862 (59.6%) had previous PCI (mean age 68.2±7.8, female 19.4%, diabetes mellitus 35.7%, previous myocardial infarction 74.8%, multivessel PCI 38.0%). Average time from PCI to randomization was 5.4 years (SD, 4.4) and follow-up was 1.98 (SD, 0.72) years. Regardless of previous PCI, DPI versus aspirin produced consistent reductions in MACE (PCI: 4.0% versus 5.5%; hazard ratio [HR], 0.74 [95% CI, 0.61-0.88]; no PCI: 4.4% versus 5.7%; HR, 0.76 [95% CI, 0.61-0.94], -interaction=0.85) and mortality (PCI: 2.5% versus 3.5%; HR, 0.73 [95% CI, 0.58-0.92]; no PCI: 4.1% versus 5.0%; HR, 0.80 [95% CI, 0.64-1.00], -interaction=0.59), but increased major bleeding (PCI: 3.3% versus 2.0%; HR, 1.72 [95% CI, 1.34-2.21]; no PCI: 2.9% versus 1.8%; HR, 1.58 [95% CI, 1.15-2.17], -interaction=0.68). In those with previous PCI, DPI compared with aspirin produced consistent (robust) reductions in MACE irrespective of time since previous PCI (as early as 1 year and as far as 10 years; -interaction=0.65), irrespective of having a previous myocardial infarction (-interaction=0.64).
DPI compared with aspirin produced consistent reductions in MACE and mortality but with increased major bleeding with or without previous PCI. Among those with previous PCI 1 year and beyond, the effects on MACE and mortality were consistent irrespective of time since last PCI. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01776424.
COMPASS 试验（使用抗凝策略的人群心血管结果）表明，与每日一次口服 100 毫克阿司匹林相比，每日两次口服 2.5 毫克利伐沙班加每日一次口服阿司匹林的双重途径抑制（DPI）可降低慢性冠状动脉综合征或外周动脉疾病患者的主要不良心血管事件（MACE）结局，包括心血管死亡、心肌梗死或中风，以及死亡率。对于有经皮冠状动脉介入治疗（PCI）史的患者，这种情况是否仍然如此尚不清楚。
在 COMPASS 的一项预设亚组分析中，我们检查了既往接受过 PCI 的慢性冠状动脉综合征患者与单独使用阿司匹林相比，接受 DPI 治疗的结局。对于既往有 PCI 的患者，我们根据既往 PCI 的时间研究了治疗效果。
在 27395 例 COMPASS 患者中，16560 例患有慢性冠状动脉综合征的患者被随机分配至 DPI 或阿司匹林组，其中 9862 例（59.6%）有既往 PCI（平均年龄 68.2±7.8 岁，女性 19.4%，糖尿病 35.7%，既往心肌梗死 74.8%，多血管 PCI 38.0%）。从 PCI 到随机分组的平均时间为 5.4 年（标准差，4.4），随访时间为 1.98 年（标准差，0.72）。无论是否有既往 PCI，DPI 与阿司匹林相比均能一致降低 MACE（PCI：4.0% vs. 5.5%；危险比[HR]，0.74 [95%CI，0.61-0.88]；无 PCI：4.4% vs. 5.7%；HR，0.76 [95%CI，0.61-0.94]，-交互作用=0.85）和死亡率（PCI：2.5% vs. 3.5%；HR，0.73 [95%CI，0.58-0.92]；无 PCI：4.1% vs. 5.0%；HR，0.80 [95%CI，0.64-1.00]，-交互作用=0.59），但增加了大出血（PCI：3.3% vs. 2.0%；HR，1.72 [95%CI，1.34-2.21]；无 PCI：2.9% vs. 1.8%；HR，1.58 [95%CI，1.15-2.17]，-交互作用=0.68）。对于既往有 PCI 的患者，与阿司匹林相比，DPI 能一致（稳健）降低 MACE，与既往 PCI 时间无关（最早 1 年，最长 10 年；-交互作用=0.65），与是否有既往心肌梗死无关（-交互作用=0.64）。
与阿司匹林相比，DPI 能一致降低 MACE 和死亡率，但增加了有或无既往 PCI 的大出血风险。对于既往有 PCI 1 年及以上的患者，MACE 和死亡率的影响与时间无关。
