Ticagrelor versus Clopidogrel in Symptomatic Peripheral Artery Disease

EUCLID Trial Steering Committee and Investigators, William R. Hiatt, F. Gerry R. Fowkes, Gretchen Heizer, Jeffrey S. Berger, Iris Baumgartner, Peter Held, Brian G. Katona, Kenneth W. Mahaffey, Lars Norgren, W. Schuyler Jones, Juuso Blomster, Marcus Millegård, Craig Reist, Manesh R. Patel (Lead / Corresponding author)

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Abstract

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.

Original languageEnglish
Pages (from-to)32-40
Number of pages9
JournalNew England Journal of Medicine
Volume376
Issue number1
DOIs
Publication statusPublished - 5 Jan 2017

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clopidogrel
Peripheral Arterial Disease
Ankle Brachial Index
Extremities
Confidence Intervals
Hemorrhage
Ticagrelor
Ischemia

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EUCLID Trial Steering Committee and Investigators, Hiatt, W. R., Fowkes, F. G. R., Heizer, G., Berger, J. S., Baumgartner, I., ... Patel, M. R. (2017). Ticagrelor versus Clopidogrel in Symptomatic Peripheral Artery Disease. New England Journal of Medicine, 376(1), 32-40. https://doi.org/10.1056/NEJMoa1611688
EUCLID Trial Steering Committee and Investigators ; Hiatt, William R. ; Fowkes, F. Gerry R. ; Heizer, Gretchen ; Berger, Jeffrey S. ; Baumgartner, Iris ; Held, Peter ; Katona, Brian G. ; Mahaffey, Kenneth W. ; Norgren, Lars ; Jones, W. Schuyler ; Blomster, Juuso ; Millegård, Marcus ; Reist, Craig ; Patel, Manesh R. / Ticagrelor versus Clopidogrel in Symptomatic Peripheral Artery Disease. In: New England Journal of Medicine. 2017 ; Vol. 376, No. 1. pp. 32-40.
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abstract = "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.",
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EUCLID Trial Steering Committee and Investigators, Hiatt, WR, Fowkes, FGR, Heizer, G, Berger, JS, Baumgartner, I, Held, P, Katona, BG, Mahaffey, KW, Norgren, L, Jones, WS, Blomster, J, Millegård, M, Reist, C & Patel, MR 2017, 'Ticagrelor versus Clopidogrel in Symptomatic Peripheral Artery Disease', New England Journal of Medicine, vol. 376, no. 1, pp. 32-40. https://doi.org/10.1056/NEJMoa1611688

Ticagrelor versus Clopidogrel in Symptomatic Peripheral Artery Disease. / EUCLID Trial Steering Committee and Investigators; Hiatt, William R.; Fowkes, F. Gerry R.; Heizer, Gretchen; Berger, Jeffrey S.; Baumgartner, Iris; Held, Peter; Katona, Brian G.; Mahaffey, Kenneth W.; Norgren, Lars; Jones, W. Schuyler; Blomster, Juuso; Millegård, Marcus; Reist, Craig; Patel, Manesh R. (Lead / Corresponding author).

In: New England Journal of Medicine, Vol. 376, No. 1, 05.01.2017, p. 32-40.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Ticagrelor versus Clopidogrel in Symptomatic Peripheral Artery Disease

AU - EUCLID Trial Steering Committee and Investigators

AU - Hiatt, William R.

AU - Fowkes, F. Gerry R.

AU - Heizer, Gretchen

AU - Berger, Jeffrey S.

AU - Baumgartner, Iris

AU - Held, Peter

AU - Katona, Brian G.

AU - Mahaffey, Kenneth W.

AU - Norgren, Lars

AU - Jones, W. Schuyler

AU - Blomster, Juuso

AU - Millegård, Marcus

AU - Reist, Craig

AU - Patel, Manesh R.

AU - Belch, Jill

PY - 2017/1/5

Y1 - 2017/1/5

N2 - 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.

AB - 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.

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DO - 10.1056/NEJMoa1611688

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C2 - 27959717

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VL - 376

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JO - New England Journal of Medicine

JF - New England Journal of Medicine

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EUCLID Trial Steering Committee and Investigators, Hiatt WR, Fowkes FGR, Heizer G, Berger JS, Baumgartner I et al. Ticagrelor versus Clopidogrel in Symptomatic Peripheral Artery Disease. New England Journal of Medicine. 2017 Jan 5;376(1):32-40. https://doi.org/10.1056/NEJMoa1611688