动脉粥样硬化血栓形成风险分层以及vorapaxar在稳定型缺血性心脏病和既往心肌梗死患者中的疗效与安全性

Atherothrombotic Risk Stratification and the Efficacy and Safety of Vorapaxar in Patients With Stable Ischemic Heart Disease and Previous Myocardial Infarction.

作者信息

Bohula Erin A, Bonaca Marc P, Braunwald Eugene, Aylward Philip E, Corbalan Ramon, De Ferrari Gaetano M, He Ping, Lewis Basil S, Merlini Piera A, Murphy Sabina A, Sabatine Marc S, Scirica Benjamin M, Morrow David A

机构信息

From the TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (E.A.B., M.P.B., E.B., P.H., S.A.M., M.S.S., B.M.S., D.A.M.); South Australian Health and Research Institute, Flinders University and Medical Centre, Adelaide (P.E.A.); Division of Cardiovascular Diseases, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago (R.C.); Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (G.M.D.F.); Lady Davis Carmel Medical Center and the Ruth and Bruce Rappaport School of Medicine, Technion, Haifa, Israel (B.S.L.); and IV Divisione Cardiologia, Azienda Ospedaliera Niguarda Ca' Granda, Milan, Italy (P.A.M.).

出版信息

Circulation. 2016 Jul 26;134(4):304-13. doi: 10.1161/CIRCULATIONAHA.115.019861.

DOI:10.1161/CIRCULATIONAHA.115.019861

PMID:27440003

Abstract

BACKGROUND

Patients with stable ischemic heart disease and previous myocardial infarction (MI) vary in their risk for recurrent cardiovascular events. Atherothrombotic risk assessment may be useful to identify high-risk patients who have the greatest potential to benefit from more intensive secondary preventive therapy such as treatment with vorapaxar.

METHODS

We identified independent clinical indicators of atherothrombotic risk among 8598 stable, placebo-treated patients with a previous MI followed up for 2.5 years (median) in TRA 2°P-TIMI 50 [Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-TIMI 50]. The efficacy and safety of vorapaxar (SCH 530348; MK-5348) were assessed by baseline risk among patients with previous MI without prior stroke or transient ischemic attack for whom there is a clinical indication for vorapaxar. End points were cardiovascular death, MI, or ischemic stroke and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) severe bleeding.

RESULTS

The 9 independent risk predictors were age, diabetes mellitus, hypertension, smoking, peripheral arterial disease, previous stroke, previous coronary bypass grafting, heart failure, and renal dysfunction. A simple integer-based scheme using these predictors showed a strong graded relationship with the rate of cardiovascular death/MI/ischemic stroke and the individual components (P for trend <0.001 for all). High-risk patients (≥3 risk indicators; 20% of population) had a 3.2% absolute risk reduction in cardiovascular disease/MI/ischemic stroke with vorapaxar, and intermediate-risk patients (1-2 risk indicators; 61%) had a 2.1% absolute risk reduction (P<0.001 each), translating to a number needed to treat of 31 and 48. Bleeding increased across risk groups (P for trend<0.01); however, net clinical outcome was increasingly favorable with vorapaxar across risk groups. Fatal bleeding or intracranial hemorrhage was 0.9% with both treatments in high-risk patients.

CONCLUSIONS

Stratification of baseline atherothrombotic risk can assist with therapeutic decision making for vorapaxar use for secondary prevention after MI.

CLINICAL TRIAL REGISTRATION

URL: https://www.clinicaltrials.gov. Unique identifier: NCT00526474.

摘要

背景

患有稳定型缺血性心脏病且既往有心肌梗死（MI）的患者发生心血管事件复发的风险各不相同。动脉粥样硬化血栓形成风险评估可能有助于识别那些最有可能从更强化的二级预防治疗（如使用vorapaxar治疗）中获益的高危患者。

方法

我们在8598例既往有MI且接受安慰剂治疗的稳定患者中确定了动脉粥样硬化血栓形成风险的独立临床指标，这些患者在TRA 2°P-TIMI 50[动脉粥样硬化血栓形成缺血事件二级预防中的凝血酶受体拮抗剂-TIMI 50]研究中进行了2.5年（中位数）的随访。对于既往有MI且无既往卒中或短暂性脑缺血发作且有vorapaxar临床指征的患者，根据基线风险评估vorapaxar（SCH 530348；MK-5348）的疗效和安全性。终点为心血管死亡、MI或缺血性卒中以及GUSTO（全球开放闭塞冠状动脉策略的应用）严重出血。

结果

9个独立的风险预测因素为年龄、糖尿病、高血压、吸烟、外周动脉疾病、既往卒中、既往冠状动脉旁路移植术、心力衰竭和肾功能不全。使用这些预测因素的基于简单整数的方案显示与心血管死亡/MI/缺血性卒中发生率及各个组成部分有很强的分级关系（所有趋势P<0.001）。高危患者（≥3个风险指标；占人群的20%）使用vorapaxar后心血管疾病/MI/缺血性卒中的绝对风险降低3.2%，中危患者（1-2个风险指标；61%）的绝对风险降低2.1%（各P<0.001），相应的治疗所需人数分别为31和48。出血在各风险组中均增加（趋势P<0.01）；然而，各风险组中vorapaxar的净临床结局越来越有利。高危患者中两种治疗的致命性出血或颅内出血均为0.9%。