Hess Connie N, Clare Robert M, Neely Megan L, Tricoci Pierluigi, Mahaffey Kenneth W, James Stefan K, Alexander John H, Held Claes, Lopes Renato D, Fox Keith A A, White Harvey D, Wallentin Lars, Armstrong Paul W, Harrington Robert A, Ohman Erik Magnus, Roe Matthew T
Division of Cardiology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO.
Duke Clinical Research Institute, Durham, NC.
Am Heart J. 2017 May;187:194-203. doi: 10.1016/j.ahj.2017.01.016. Epub 2017 Feb 21.
Acute coronary syndrome (ACS) trials typically use a composite primary outcome (myocardial infarction [MI], stroke, or cardiovascular death), but differential patient characteristics, timing, and consequences associated with individual component end points as first events have not been well studied. We compared patient characteristics and prognostic significance associated with first cardiovascular events in the post-ACS setting for initially stabilized patients.
We combined patient-level data from 4 trials of post-ACS antithrombotic therapies (PLATO, APPRAISE-2, TRACER, and TRILOGY ACS) to characterize the timing of and characteristics associated with first cardiovascular events (MI, stroke, or cardiovascular death). Landmark analysis at 7 days after index ACS presentation was used to focus on spontaneous, postdischarge events that were not confounded by in-hospital procedural complications. Using a competing risk framework, we tested for differential associations between prespecified covariates and the occurrence of nonfatal stroke vs MI as the first event, and we examined subsequent events after the first nonfatal event.
Among 46,694 patients with a median follow-up of 358 (25th, 75th percentiles 262, 486) days, a first ischemic event occurred in 4,307 patients (9.2%) as follows: MI in 5.8% (n = 2,690), stroke in 1.0% (n = 477), and cardiovascular death in 2.4% (n = 1,140). Older age, prior stroke/transient ischemic attack, prior atrial fibrillation, and higher diastolic blood pressure were associated with a significantly greater risk of stroke vs MI, whereas prior percutaneous coronary intervention was associated with a greater risk of MI vs stroke. Second events occurred in 32% of those with a first nonfatal stroke at a median of 13 (3, 59) days after the first event and in 32% of those with a first nonfatal MI at a median of 35 (5, 137) days after the first event. The most common second event was a recurrent MI among those with MI as the first event and cardiovascular death among those with stroke as the first event.
Approximately 9% of patients experienced a first cardiovascular event in the post-ACS setting during a median follow-up of 1 year. Although the profile and prognostic implications of stroke vs MI as the first nonfatal event differ substantially, approximately one-third of these patients experienced a second event, typically soon after the first event. These findings have implications for improving post-ACS care and influencing the design of future cardiovascular trials.
急性冠状动脉综合征（ACS）试验通常采用复合主要终点（心肌梗死[MI]、卒中或心血管死亡），但与各个组成终点作为首发事件相关的患者特征差异、发生时间及后果尚未得到充分研究。我们比较了ACS后病情初步稳定患者首次心血管事件的患者特征及预后意义。
我们合并了4项ACS后抗栓治疗试验（PLATO、APPRAISE - 2、TRACER和TRILOGY ACS）的患者水平数据，以描述首次心血管事件（MI、卒中或心血管死亡）的发生时间及相关特征。在ACS首次发病后7天进行标志性分析，重点关注未受住院手术并发症干扰的出院后自发性事件。使用竞争风险框架，我们测试了预先指定的协变量与非致命性卒中与MI作为首发事件发生之间的差异关联，并检查了首次非致命事件后的后续事件。
在46,694例患者中，中位随访时间为358（第25、75百分位数为262、486）天，4,307例患者（9.2%）发生了首次缺血性事件，情况如下：MI发生率为5.8%（n = 2,690），卒中发生率为1.0%（n = 477），心血管死亡发生率为2.4%（n = 1,140）。年龄较大、既往有卒中/短暂性脑缺血发作、既往有房颤以及舒张压较高与卒中发生风险显著高于MI相关，而既往经皮冠状动脉介入治疗与MI发生风险高于卒中相关。32%首次发生非致命性卒中的患者在首次事件后中位13（3，59）天发生了第二次事件，32%首次发生非致命性MI的患者在首次事件后中位35（5，137）天发生了第二次事件。最常见的第二次事件是首次事件为MI的患者发生复发性MI，首次事件为卒中的患者发生心血管死亡。
在中位1年的随访期间，约9%的患者在ACS后发生了首次心血管事件。虽然卒中与MI作为首次非致命事件的特征及预后影响有很大差异，但这些患者中约三分之一发生了第二次事件，通常在首次事件后不久。这些发现对改善ACS后护理及影响未来心血管试验设计具有重要意义。
