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Stroke in Patients With Peripheral Artery Disease
Study Questions:
What is the incidence of ischemic/hemorrhagic stroke and transient ischemic attack (TIA) in patients with symptomatic peripheral artery disease (PAD), predictors of stroke in patients with PAD, and the rate of stroke in ticagrelor- and clopidogrel-treated PAD patients?
Methods:
The investigators conducted a substudy from the EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) trial, which randomized 13,885 patients with symptomatic PAD to receive monotherapy with ticagrelor or clopidogrel for the prevention of major adverse cardiovascular events (cardiovascular death, myocardial infarction, or ischemic stroke). Ischemic/hemorrhagic stroke and TIA were adjudicated and measured as incidence rates post-randomization and cumulative incidence (per patient-years). Post hoc multivariable competing risk hazards analyses were performed using baseline characteristics to determine factors associated with all-cause stroke in patients with PAD. Competing risk survival analyses were performed, where the stroke endpoints were the events of interest and deaths without prior strokes were specified as competing risks.
Results:
A total of 458 cerebrovascular events in 424 patients (317 ischemic strokes, 39 hemorrhagic strokes, and 102 TIAs) occurred over a median follow-up of 30 months, for a cumulative incidence of 0.87, 0.11, and 0.27 per 100 patient-years, respectively. Age, prior stroke, prior atrial fibrillation/flutter, diabetes mellitus, geographic region, ankle-brachial index <0.60, prior amputation, and systolic blood pressure were independent baseline factors associated with the occurrence of all-cause stroke. After adjustment for baseline factors, the rates of ischemic stroke and all-cause stroke remained lower in patients treated with ticagrelor as compared with those receiving clopidogrel. There was no significant difference in the incidence of hemorrhagic stroke or TIA between the two treatment groups.
Conclusions:
The authors concluded that comorbidities such as age, prior stroke, prior atrial fibrillation/flutter, diabetes mellitus, higher blood pressure, prior amputation, lower ankle-brachial index, and geographic region were each independently associated with the occurrence of all-cause stroke.
Perspective:
This substudy reports that in patients with symptomatic PAD, ischemic stroke and TIA occur frequently over time. Furthermore, age, prior stroke, prior atrial fibrillation/flutter, diabetes mellitus, higher blood pressure, prior amputation, lower ankle-brachial index, and geographic region were each independently associated with all-cause stroke. Also, use of ticagrelor, as compared with clopidogrel, was associated with a lower adjusted rate of ischemic and all-cause stroke but needs to be tempered by the overall absence of benefit for ticagrelor on the primary composite endpoint of the EUCLID trial. Additional studies are needed to define optimal medical management and risk reduction of stroke in patients with PAD with the caveat that long-term prevention strategies may differ from acute prevention and that strategies may need to be adjusted based on when they are initiated relative to the initial vascular event.
Keywords: Adenosine, Amputation, Ankle Brachial Index, Atrial Fibrillation, Atrial Flutter, Blood Pressure, Brain Ischemia, Diabetes Mellitus, Hemorrhage, Ischemic Attack, Transient, Myocardial Infarction, Peripheral Arterial Disease, Primary Prevention, Stroke, Vascular Diseases
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