What are the incidence, characteristics, and relevance of myocardial infarction (MI) in patients with peripheral artery disease (PAD)?
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.
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.
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.
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.
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.
ClinicalTrials.gov Identifier: NCT01732822
Olivier CB, Mulder H, Hiatt WR, et al. Incidence, Characteristics, and Outcomes of Myocardial Infarction in Patients With Peripheral Artery Disease: Insights From the EUCLID Trial. JAMA Cardiol. 2019;4(1):7–15. doi:10.1001/jamacardio.2018.4171
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