Myocardial infarction (MI) was associated with an increased risk of hospitalization for acute limb ischemia events and cardiovascular death, and 4.9% of patients with peripheral artery disease (PAD) experienced MI within a median follow-up time period of 30 months, according to a study published in JAMA Cardiology.

The current study is a secondary analysis of the randomized, double-blind, clinical trial Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease (EUCLID, Identifier: NCT01732822). The EUCLID trial followed 13,885 participants (72.0% male, median age 66 [60-73] years) on clopidogrel or ticagrelor monotherapy for a median follow-up period of 30 months.

For the current analysis, researchers evaluated the incidence and type of MI among these patients during follow-up to determine the association of MI with acute limb ischemia and cardiovascular mortality.

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MI events were classified as types 1, 2, 3, 4a, 4b, or 5 (spontaneous, secondary, sudden cardiac death, <48 hours after percutaneous coronary intervention, definite stent thrombosis, and <72 hours after coronary artery bypass graft, respectively).

Stepwise selection was used to develop a multivariate regression model identifying factors associated with MI, and a multivariate, time-dependent Cox regression analysis was used to identify the associations of MI with acute limb ischemia hospitalizations and cardiovascular death.

Of the total patient population, 683 (4.9%) experienced MI during the follow-up period, for an average of 2.4 events per 100 patient-years. 

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These patients were older (median age 69 [62-75] years vs 66 [60-72] years) and more likely to have a previous lower extremity revascularization (68.2% [466 of 683] vs 56.1% [7409 of 13,202]) or diabetes (51.1% [349 of 683] vs 37.8% [4996 of 13,202]) than patients who did not experience MI.

Most events were type 1 (59.3%, n=405), followed by type 2 (34.6%, n=236). Few events were types 3, 4a, 4b, or 5 (1.8%, 2.0%, 1.6%, and 0.7%, respectively).

After randomization, MI was independently associated with hospitalizations for acute limb ischemia (adjusted hazard ratio [HR], 2.5; 95% CI, 1.3-5.0; =.008) and cardiovascular death (adjusted HR, 9.0; 95% CI, 7.3-11.2; <.001).

“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,” the study authors concluded.


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 [published online December 12, 2018]. JAMA Cardiol. doi: 10.1001/jamacardio.2018.4171