PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Am J Cardiol. 2018 Dec 1;122(11):1896-1901. doi: 10.1016/j.amjcard.2018.08.034. Epub 2018 Sep 7.
Patients with both acute coronary syndromes (ACS) and congestive heart failure are at an increased risk of recurrent cardiovascular (CV) events attributed in part to both excess thrombin generation and impaired fibrinolysis. We hypothesized that patients with the overlap of ACS and CHF would thus derive particular benefit from antithrombotic therapy with rivaroxaban. ATLAS-ACS-2 Thrombolysis in Myocardial Infarction-51 was a double-blind, multicenter, phase 3 clinical trial that randomized patients within 7 days of an ACS event to standard of care plus either rivaroxaban 2.5 mg BID, 5 mg BID, or placebo (n = 15,526). In this post hoc subgroup analysis, subjects with a history of CHF at randomization (n = 1,694) were evaluated. Among subjects with a history of CHF, both rivaroxaban doses reduced the primary composite end point of CV death, myocardial infarction, or stroke (2.5 mg BID vs placebo: hazard ratio [HR] 0.59, 95% confidence interval [CI] (0.42, 0.81), p = 0.001; 5 mg BID vs placebo: HR 0.61, 95% CI (0.44, 0.84), p = 0.002; p interaction = 0.006). Both doses of rivaroxaban reduced CV mortality (rivaroxaban 2.5 mg BID vs placebo: 4.1% vs 9.0%, HR 0.45, 95% CI [0.27, 0.74], p = 0.002; rivaroxaban 5 mg BID vs placebo: 5.8% vs 9.0%, HR 0.62, 95% CI [0.40, 0.96], p = 0.031) as well as all-cause mortality. There was no significant increase in noncoronary artery bypass graft-related Thrombolysis in Myocardial Infarction major bleeding with either dose of rivaroxaban as compared with placebo (rivaroxaban 2.5 mg BID = 0.4% vs rivaroxaban 5 mg BID = 1.1% vs placebo = 0.5%). Rivaroxaban also did not increase either intracranial hemorrhage or fatal bleeding. In conclusion, in ACS subjects with a history of CHF, secondary prevention with rivaroxaban reduced the composite of CV death, myocardial infarction, or stroke without an increase in noncoronary artery bypass graft-related major bleeding. These findings require further prospective evaluation in an adequately powered phase 3 study.
患者同时患有急性冠脉综合征（ACS）和充血性心力衰竭（CHF），发生心血管（CV）事件的复发风险增加，部分原因是凝血酶生成过多和纤溶受损。我们假设，重叠患有 ACS 和 CHF 的患者将特别受益于利伐沙班的抗血栓治疗。ATLAS-ACS-2 心肌梗死溶栓 51 是一项双盲、多中心、3 期临床试验，该试验将 ACS 事件发生后 7 天内的患者随机分为标准治疗加利伐沙班 2.5 mg BID、5 mg BID 或安慰剂组（n=15526）。在这项事后亚组分析中，评估了随机时有 CHF 病史的受试者。在有 CHF 病史的受试者中，两种剂量的利伐沙班均降低了 CV 死亡、心肌梗死或中风的主要复合终点（2.5 mg BID 与安慰剂：风险比 [HR] 0.59，95%置信区间 [CI]（0.42，0.81），p=0.001；5 mg BID 与安慰剂：HR 0.61，95%CI（0.44，0.84），p=0.002；p 交互=0.006）。两种剂量的利伐沙班均降低了 CV 死亡率（利伐沙班 2.5 mg BID 与安慰剂：4.1% vs 9.0%，HR 0.45，95%CI[0.27，0.74]，p=0.002；利伐沙班 5 mg BID 与安慰剂：5.8% vs 9.0%，HR 0.62，95%CI[0.40，0.96]，p=0.031）和全因死亡率。与安慰剂相比，两种剂量的利伐沙班均未增加非冠状动脉旁路移植术相关的心肌梗死大出血（利伐沙班 2.5 mg BID=0.4%vs利伐沙班 5 mg BID=1.1%vs安慰剂=0.5%）。利伐沙班也没有增加颅内出血或致命性出血。总之，在 ACS 合并 CHF 病史的患者中，利伐沙班的二级预防降低了 CV 死亡、心肌梗死或中风的复合终点，而不增加非冠状动脉旁路移植术相关的大出血。这些发现需要在一项充分有力的 3 期研究中进一步前瞻性评估。
