Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, California.
Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina.
JAMA Cardiol. 2019 Jan 1;4(1):7-15. doi: 10.1001/jamacardio.2018.4171.
Patients with peripheral artery disease (PAD) are at high risk for myocardial infarction (MI).
To characterize the incidence and types of MI in a PAD population, identify factors associated with MI, and determine the association of MI with cardiovascular mortality and acute limb ischemia.
DESIGN, SETTING, AND PARTICIPANTS: The Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease (EUCLID) was a double-blind randomized clinical trial conducted at 811 sites in 28 countries that randomized 13 885 patients with symptomatic PAD to monotherapy with ticagrelor or clopidogrel. Participants had an ankle-brachial index (ABI) of 0.80 or less or previous lower extremity revascularization. Median follow-up was 30 months. For these analyses, patients were evaluated for MI occurrence during follow-up irrespective of treatment. Data were analyzed from June 2017 to September 2018.
An adjudication clinical events committee classified MI as type 1 (spontaneous), type 2 (secondary), type 3 (sudden cardiac death), type 4a (less than 48 hours after percutaneous coronary intervention), type 4b (definite stent thrombosis), or type 5 (less than 72 hours after coronary artery bypass graft). A multivariate regression model was developed by stepwise selection to identify factors associated with MI, and a time-dependent multivariate Cox regression analysis was performed to determine the association of MI with cardiovascular death and acute limb ischemia requiring hospitalization.
Of the 13 885 patients included in this analysis, 9997 (72.0%) were male, and the median (interquartile range) age was 66 (60-73) years. Myocardial infarction occurred in 683 patients (4.9%; 2.4 events per 100 patient-years) during a median follow-up of 30 months. Patients experiencing MI were older (median [interquartile range] age, 69 [62-75] vs 66 [60-72] years), more likely to have diabetes (349 of 683 [51.1%] vs 4996 of 13 202 [37.8%]) or a previous lower extremity revascularization (466 of 683 [68.2%] vs 7409 of 13 202 [56.1%]), and had a lower ABI (if included by ABI) compared with censored patients. Of the 683 patients with MI during follow-up, the most common MI type was type 1 (405 [59.3%]), followed by type 2 (236 [34.6%]), type 4a (14 [2.0%]), type 3 (12 [1.8%]), type 4b (11 [1.6%]), and type 5 (5 [0.7%]). Postrandomization MI was independently associated with cardiovascular death (adjusted hazard ratio, 9.0; 95% CI, 7.3-11.2; P < .001) and acute limb ischemia requiring hospitalization (adjusted hazard ratio, 2.5; 95% CI, 1.3-5.0; P = .008).
Approximately 5% of patients with symptomatic PAD had an MI during a median follow-up of 30 months. Type 1 MI (spontaneous) was the most common MI type; however, one-third of MIs were type 2 MI (secondary). More research is needed to identify therapies to reduce the risk of MI in patients with PAD and to improve management of type 2 MI.
ClinicalTrials.gov Identifier: NCT01732822.
重要性：外周动脉疾病（PAD）患者有发生心肌梗死（MI）的高风险。
目的：描述 PAD 患者中 MI 的发生率和类型，确定与 MI 相关的因素，并确定 MI 与心血管死亡和急性肢体缺血之间的关联。
设计、地点和参与者：比较外周动脉疾病患者心血管影响的替格瑞洛和氯吡格雷（EUCLID）研究是一项在 28 个国家的 811 个地点进行的双盲随机临床试验，纳入 13885 例有症状 PAD 患者，随机分为替格瑞洛或氯吡格雷单药治疗。参与者踝肱指数（ABI）为 0.80 或更低，或有下肢血管重建史。中位随访时间为 30 个月。对于这些分析，无论治疗如何，患者在随访期间都要评估 MI 的发生情况。数据于 2017 年 6 月至 2018 年 9 月进行分析。
主要结局和测量：由一个裁定临床事件委员会将 MI 分类为 1 型（自发性）、2 型（继发性）、3 型（心源性猝死）、4a 型（经皮冠状动脉介入治疗后 48 小时内）、4b 型（明确的支架血栓形成）或 5 型（经皮冠状动脉介入治疗后 72 小时内）。采用逐步选择的方法建立多元回归模型，确定与 MI 相关的因素，并采用时间依赖性多元 Cox 回归分析，确定 MI 与心血管死亡和需要住院治疗的急性肢体缺血之间的关联。
结果：在本分析中纳入的 13885 例患者中，9997 例（72.0%）为男性，中位（四分位间距）年龄为 66（6073）岁。在中位 30 个月的随访期间，683 例（4.9%；每 100 患者-年 2.4 例）患者发生 MI。发生 MI 的患者年龄更大（中位数[四分位间距]年龄，69[6275]岁 vs 66[6072]岁）、更可能患有糖尿病（349 例[51.1%] vs 4996 例[37.8%]）或有下肢血管重建史（466 例[68.2%] vs 7409 例[56.1%]），并且 ABI 较低（如果按 ABI 包括）与未删失的患者相比。在随访期间发生 MI 的 683 例患者中，最常见的 MI 类型为 1 型（405 例[59.3%]），其次是 2 型（236 例[34.6%]）、4a 型（14 例[2.0%]）、3 型（12 例[1.8%]）、4b 型（11 例[1.6%]）和 5 型（5 例[0.7%]）。随机分组后的 MI 与心血管死亡（调整后的危险比，9.0；95%CI，7.311.2；P<0.001）和需要住院治疗的急性肢体缺血（调整后的危险比，2.5；95%CI，1.3~5.0；P=0.008）独立相关。
结论和相关性：在中位 30 个月的随访中，约 5%的有症状 PAD 患者发生 MI。1 型 MI（自发性）是最常见的 MI 类型；然而，三分之一的 MI 是 2 型 MI（继发性）。需要进一步研究以确定降低 PAD 患者 MI 风险的治疗方法，并改善 2 型 MI 的管理。
试验注册：ClinicalTrials.gov 标识符：NCT01732822。
