Background and Purpose- Predictors of
stroke and
transient ischemic attack (TIA) in patients with
peripheral artery disease (PAD) are poorly understood. The primary aims of this analysis were to (1) determine the incidence of ischemic/
hemorrhagic stroke and TIA in patients with symptomatic PAD, (2) identify predictors of
stroke in patients with PAD, and (3) compare the rate of
stroke in
ticagrelor- and
clopidogrel-treated patients. Methods- EUCLID (Examining Use of
Ticagrelor in
Peripheral Artery Disease) 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 postrandomization 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. 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 2 treatment groups. Conclusions- In patients with symptomatic PAD,
ischemic stroke and TIA occur frequently over time. 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. Use of
ticagrelor, as compared with
clopidogrel, was associated with a lower adjusted rate of ischemic and all-cause
stroke. Further study is needed to optimize medical management and risk reduction of all-cause
stroke in patients with PAD. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01732822.