Polyvascular Disease and Risk of MACE in PAD

Study Questions:

What is the risk of cardiac and limb ischemic events among patients with peripheral artery disease (PAD) and polyvascular disease?


The authors performed a post hoc secondary analysis of the EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) trial, which compared ticagrelor to clopidogrel in patients with symptomatic PAD. This analysis compared ischemic outcomes among patients with PAD only, PAD plus coronary artery disease (CAD), PAD plus cerebrovascular disease (CVD), and PAD plus CAD and CVD. The primary endpoint was a composite of cardiovascular death, myocardial infarction (MI), or ischemic stroke. The secondary endpoints included acute limb ischemia leading to hospitalization, major amputation, lower extremity revascularization, and Thrombolysis in MI (TIMI) major bleeding.


Among the 13,885 patients in the EUCLID study, 7,804 (56.2%) had PAD alone, 2,639 (19.0%) had PAD plus CAD, 2,049 (14.8%) had PAD plus CVD, and 1,393 (10.0%) had PAD plus CAD and CVD. Compared to patients with PAD alone, adjusted hazard ratios (HRs) for MACE were higher for all groups of patients with polyvascular disease (1.34-1.99, p < 0.001 for each). Similarly, the adjusted HR was higher for lower extremity revascularization (1.17-1.34), but there was not an increased risk of acute limb ischemia, major amputation, or TIMI major bleeding.


The authors concluded that the risk of MACE and lower extremity revascularization were increased in patients with polyvascular disease as compared to patients with PAD alone.


This study adds to the growing body of literature describing poor outcomes for patients with polyvascular disease involving the lower extremities and at least one other arterial bed (coronary or cerebral). While in the advent of new therapies (e.g., very low dose rivaroxaban, PCSK9 inhibitor therapy) for this population, it is imperative that good baseline medical therapy is initiated. This means high-intensity statins, antiplatelet therapies, and blood pressure control (often with an angiotensin-converting enzyme inhibitor). Additionally, cardiovascular providers caring for patients with CAD should screen for symptomatic PAD to help with prognosis and optimizing treatment.

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Prevention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Cardiac Surgery and Arrhythmias, Interventions and Coronary Artery Disease, Interventions and Vascular Medicine

Keywords: Amputation, Brain Ischemia, Coronary Artery Disease, Hemorrhage, Myocardial Infarction, Myocardial Ischemia, Myocardial Revascularization, Peripheral Arterial Disease, Risk, Secondary Prevention, Stroke, Vascular Diseases

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