Physicians' Academy for Cardiovascular Education

High rate of total cardiovascular and limb events in patients with peripheral artery disease

Total Cardiovascular and Limb Events and the Impact of Polyvascular Disease in Chronic Symptomatic Peripheral Artery Disease

Literature - Szarek M, Hess C, Patel MR, et al. - J Am Heart Assoc. 2022 May 27;e025504. doi: 10.1161/JAHA.122.025504.

Introduction and methods


Patients with peripheral arterial disease have an increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) [1]. However, most clinical trials report only the occurrence of first cardiovascular and limb events. Data on the total number – i.e., first and subsequent – events in patients with chronic stable symptomatic peripheral arterial disease are limited. Furthermore, it is unclear what the effect of treatment with ticagrelor or clopidogrel is on the total number of events in these patients. Previously, the EUCLID trial showed that the number of first events did not differ between patients with symptomatic peripheral arterial disease treated with ticagrelor or clopidogrel [2].

Aim of the study

The aim of this study was to investigate the total number of cardiovascular and limb events in patients with symptomatic peripheral arterial disease, both in the total study population and in specific subgroups.


The researchers conducted a post hoc analysis of data from the EUCLID trial. In this multicenter, double-blind RCT, patients ≥50 years of age with symptomatic peripheral arterial disease were randomized to treatment with ticagrelor (90 mg 2 dd) or clopidogrel (75 mg 1 dd). Symptomatic peripheral arterial disease was defined as lower extremity revascularization more than 30 days prior to randomization or ankle-brachial index ≤ 0.80. Key exclusion criteria included: long-term dual-antiplatelet therapy, requirement for aspirin, increased risk of bleeding, long-term anticoagulation treatment and poor clopidogrel metabolizer status.


The researchers reported the following acute cardiovascular and limb events: cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, and acute limb ischemia, unstable angina, or TIA requiring hospitalization. In addition, they reported procedures, including coronary, carotid and peripheral revascularization and amputation for symptomatic peripheral arterial disease. Together, acute cardiovascular and limb events and procedures made up the total number of events.

Main results


In patients with symptomatic peripheral arterial disease, the total number of MACE and MALE is nearly double the number of first events. As more vascular territories are affected, the number of cardiovascular and limb events also increases. In particular, patients with 3 affected vascular territories have an exceptionally high risk for events. The researchers suggest that these patients may benefit from more potent antithrombotic therapy.


Show references

Find this article online at J Am Heart Assoc.

Share this page with your colleagues and friends: