急性冠状动脉综合征患者应用利伐沙班导致的致死性或不可逆转性出血和缺血事件。
Fatal or Irreversible Bleeding and Ischemic Events With Rivaroxaban in Acute Coronary Syndrome.
机构信息
Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Janssen Research and Development, Titusville, New Jersey.
出版信息
J Am Coll Cardiol. 2018 Jul 10;72(2):129-136. doi: 10.1016/j.jacc.2018.04.055.
BACKGROUND
Net clinical outcome analyses of acute coronary syndrome (ACS) mingle fatal or irreversible events with survivable or reversible events that vary significantly in clinical impact.
OBJECTIVES
A comparison of efficacy and safety limited to fatal or irreversible ischemic and adverse or seriously harmful events is one way to assess net clinical outcome and risk-benefit overall, given the fact that these events have a similar clinical impact.
METHODS
In the ATLAS ACS 2-TIMI 51 (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction) trial of rivaroxaban in the secondary prevention of events among patients with ACS treated with aspirin plus clopidogrel or ticlopidine (clopidogrel/ticlopidine) or aspirin alone, fatal and irreversible efficacy events including nonbleeding cardiovascular death, myocardial infarction, and ischemic stroke were compared to fatal or irreversible safety events, including fatal and intracranial bleeding.
RESULTS
Rivaroxaban, 2.5 mg orally twice per day, in patients treated with aspirin and clopidogrel/ticlopidine was associated with 115 (95% confidence interval [CI]: 18 to 212) fewer fatal or irreversible ischemic events (663 for placebo vs. 548 for therapy) and 10 (95% CI: -11 to 32) additional fatal or irreversible seriously harmful events (33 vs. 23 for placebo) per 10,000 patient-years of exposure. Taken together, there would be 105 (95% CI: 6 to 204) fatal or irreversible events prevented per 10,000 patient-years of exposure to rivaroxaban compared with placebo, with 11 (10 of 115) fatal or irreversible ischemic events prevented for each fatal or irreversible seriously harmful event caused. If only nonbleeding cardiovascular death is included as a fatal or irreversible event, then 95 events would be prevented per 10,000 patient-years of exposure in the group taking 2.5 mg orally twice per day.
CONCLUSIONS
Both fatal or irreversible ischemia and bleeding are clinically significant events that can be compared to assess the net clinical outcomes associated with therapy. Rivaroxaban therapy at an oral dose of 2.5 mg twice daily in patients treated with aspirin and clopidogrel is associated with a net reduction in fatal or irreversible events. (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction [ATLAS ACS 2-TIMI 51]; NCT00809965).
背景
急性冠状动脉综合征（ACS）的净临床结局分析将致命或不可逆事件与可存活或可逆转事件混为一谈，而这些事件在临床影响方面差异显著。
目的
鉴于这些事件具有相似的临床影响，仅对致命或不可逆的缺血和不良或严重有害事件进行疗效和安全性比较，是评估净临床结局和风险效益的一种方法。
方法
在接受阿司匹林加氯吡格雷或噻氯匹定（氯吡格雷/噻氯匹定）或阿司匹林治疗的 ACS 患者中，使用利伐沙班进行的 ATLAS ACS 2-TIMI 51（加用抗 Xa 治疗降低急性冠状动脉综合征患者心血管事件发生率-心肌梗死溶栓治疗）试验中，将致命和不可逆的疗效事件（包括非出血性心血管死亡、心肌梗死和缺血性卒中）与致命或不可逆的安全性事件（包括致命和颅内出血）进行比较。
结果
接受阿司匹林和氯吡格雷/噻氯匹定治疗的患者中，每日口服利伐沙班 2.5mg，2 次/天，可减少 115 例（95%置信区间[CI]：18 至 212）致命或不可逆的缺血事件（安慰剂组 663 例 vs. 治疗组 548 例），增加 10 例（95%CI：-11 至 32）致命或不可逆的严重有害事件（安慰剂组 33 例 vs. 治疗组 33 例）每 10,000 患者-年暴露。因此，与安慰剂相比，每 10,000 患者-年暴露可预防 105 例（95%CI：6 至 204）致命或不可逆事件，每发生 1 例致命或不可逆的严重有害事件，可预防 11 例（115 例中的 11 例）致命或不可逆的缺血事件。如果仅将非出血性心血管死亡作为致命或不可逆事件，那么每日口服 2.5mg 两次的组每 10,000 患者-年暴露可预防 95 例事件。
结论
致命或不可逆的缺血和出血都是有临床意义的事件，可用于评估与治疗相关的净临床结局。在接受阿司匹林和氯吡格雷治疗的患者中，每日口服 2.5mg 利伐沙班两次，与致命或不可逆事件的净减少相关。（加用抗 Xa 治疗降低急性冠状动脉综合征患者心血管事件发生率-心肌梗死溶栓治疗[ATLAS ACS 2-TIMI 51]；NCT00809965）。
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