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Original Investigation
January 2019

Incidence, Characteristics, and Outcomes of Myocardial Infarction in Patients With Peripheral Artery Disease: Insights From the EUCLID Trial

Author Affiliations
  • 1Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, California
  • 2Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
  • 3Division of Cardiology, University of Colorado School of Medicine, Aurora
  • 4CPC Clinical Research, University of Colorado School of Medicine, Aurora
  • 5Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom
  • 6Department of Medicine, New York University School of Medicine, New York
  • 7Department of Surgery, New York University School of Medicine, New York
  • 8Swiss Cardiovascular Center, Inselspital, University of Bern, Bern, Switzerland
  • 9AstraZeneca Gothenburg, Mölndal, Sweden
  • 10AstraZeneca Gaithersburg, Gaithersburg, Maryland
  • 11Faculty of Medicine and Health, Örebro University, Örebro, Sweden
  • 12Turku University Hospital, Turku, Finland
JAMA Cardiol. 2019;4(1):7-15. doi:10.1001/jamacardio.2018.4171
Key Points

Question  What are the incidence, characteristics, and relevance of myocardial infarction (MI) in patients with peripheral artery disease (PAD)?

Findings  In this secondary analysis of the randomized clinical EUCLID trial, of 13 885 patients with symptomatic PAD, 683 (4.9%) experienced MI during a median follow-up of 30 months; type 1 MI (spontaneous) was the most common type of MI, and one-third of MIs were type 2 MI (secondary). Myocardial infarction was associated with an increased risk of cardiovascular death and acute limb ischemia events.

Meaning  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.

Abstract

Importance  Patients with peripheral artery disease (PAD) are at high risk for myocardial infarction (MI).

Objective  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.

Main Outcomes and Measures  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.

Results  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).

Conclusions and Relevance  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.

Trial Registration  ClinicalTrials.gov Identifier: NCT01732822

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