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Ticagrelor versus Clopidogrel in Symptomatic Peripheral Artery Disease
Open accessAbstract
BACKGROUND: Peripheral artery disease is considered to be a manifestation of systemic atherosclerosis with associated adverse cardiovascular and limb events. Data from previous trials have suggested that patients receiving clopidogrel monotherapy had a lower risk of cardiovascular events than those receiving aspirin. We wanted to compare clopidogrel with ticagrelor, a potent antiplatelet agent, in patients with peripheral artery disease. METHODS: In this double-blind, event-driven trial, we randomly assigned 13,885 patients with symptomatic peripheral artery disease to receive monotherapy with ticagrelor (90 mg twice daily) or clopidogrel (75 mg once daily). Patients were eligible if they had an ankle-brachial index (ABI) of 0.80 or less or had undergone previous revascularization of the lower limbs. The primary efficacy end point was a composite of adjudicated cardiovascular death, myocardial infarction, or ischemic stroke. The primary safety end point was major bleeding. The median follow-up was 30 months. RESULTS: The median age of the patients was 66 years, and 72% were men; 43% were enrolled on the basis of the ABI and 57% on the basis of previous revascularization. The mean baseline ABI in all patients was 0.71, 76.6% of the patients had claudication, and 4.6% had critical limb ischemia. The primary efficacy end point occurred in 751 of 6930 patients (10.8%) receiving ticagrelor and in 740 of 6955 (10.6%) receiving clopidogrel (hazard ratio, 1.02; 95% confidence interval [CI], 0.92 to 1.13; P=0.65). In each group, acute limb ischemia occurred in 1.7% of the patients (hazard ratio, 1.03; 95% CI, 0.79 to 1.33; P=0.85) and major bleeding in 1.6% (hazard ratio, 1.10; 95% CI, 0.84 to 1.43; P=0.49). CONCLUSIONS: In patients with symptomatic peripheral artery disease, ticagrelor was not shown to be superior to clopidogrel for the reduction of cardiovascular events. Major bleeding occurred at similar rates among the patients in the two trial groups. (Funded by AstraZeneca; EUCLID ClinicalTrials.gov number, NCT01732822 .).
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Metadata
- Authors
- Hiatt, W. R., Fowkes, F. G. R., Heizer, G., Berger, J. S., Baumgartner, I., Held, P., Katona, B. G., Mahaffey, K. W., Norgren, L., Jones, W. S., Blomster, J., Millegård, M., Reist, C., & Patel, M. R.
- Affiliations
- University of Bern (CH)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2017-01-05
- Volume
- 376
- Issue
- 1
- Pages
- 32-40
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2556414715
- Cited by
- 636
- References
- 14
- Citations by year
- 2026: 26 · 2025: 42 · 2024: 57 · 2023: 59 · 2022: 60 · 2021: 85 · 2020: 75 · 2019: 80 · 2018: 87 · 2017: 60
- FWCI
- 63.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion, other-oa)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Amgen
- Bristol-Myers Squibb
- Eli Lilly and Company
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Purdue University
- Boston Scientific Corporation
- Cook Medical
- Purdue Pharma
- MyoKardia
- Mitsubishi Tanabe Pharma Corporation
- St. Jude Medical
- Abbott Vascular
- Janssen Research and Development
- Duke Clinical Research Institute
- Daiichi Sankyo Europe
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Peripheral Artery Disease Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Coronary Interventions and Diagnostics
- Keywords
- ticagrelor, clopidogrel, peripheral arterial disease, antiplatelet therapy, major bleeding, acute limb ischemia, cardiovascular events, ankle-brachial index, critical limb ischemia, claudication, lower extremity revascularization, cardiovascular mortality, ischemic stroke, myocardial infarction, P2Y12 inhibitors, aspirin, atherosclerosis
- MeSH terms
- Clopidogrel, Ticagrelor, Adenosine, Aged, Cardiovascular Diseases, Double-Blind Method, Female, Hemorrhage, Humans, Intermittent Claudication, Ischemia, Leg, Male, Middle Aged, Platelet Aggregation Inhibitors, Ticlopidine, Kaplan-Meier Estimate, Peripheral Arterial Disease, Purinergic P2Y Receptor Antagonists
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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