W Schuyler Jones1, Iris Baumgartner1, William R Hiatt1, Gretchen Heizer1, Michael S Conte1, Christopher J White1, Jeffrey S Berger1, Peter Held1, Brian G Katona1, Kenneth W Mahaffey1, Lars Norgren1, Juuso Blomster1, Marcus Millegård1, Craig Reist1, Manesh R Patel1, F Gerry R Fowkes2. 1. From Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (W.S.J., G.H., C.R., M.P.P.); Swiss Cardiovascular Centre, Inselspital, Bern University Hospital, University of Bern, Switzerland (I.B.); University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Department of Surgery, University of California San Francisco (M.S.C.); Department of Cardiology, Ochsner Clinical School, University of Queensland, Australia (C.J.W.); Ochsner Medical Center, New Orleans, LA (C.J.W.); Departments of Medicine and Surgery, New York University School of Medicine (J.S.B.); AstraZeneca Gothenburg, Mölndal, Sweden (P.H., J.B., M.M.); AstraZeneca Gaithersburg, MD (B.G.K.); Stanford Center for Clinical Research, Stanford University School of Medicine, CA (K.W.M.); Faculty of Medicine and Health, Örebro University, Sweden (L.N.); and Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, UK (F.G.R.F.). 2. From Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (W.S.J., G.H., C.R., M.P.P.); Swiss Cardiovascular Centre, Inselspital, Bern University Hospital, University of Bern, Switzerland (I.B.); University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Department of Surgery, University of California San Francisco (M.S.C.); Department of Cardiology, Ochsner Clinical School, University of Queensland, Australia (C.J.W.); Ochsner Medical Center, New Orleans, LA (C.J.W.); Departments of Medicine and Surgery, New York University School of Medicine (J.S.B.); AstraZeneca Gothenburg, Mölndal, Sweden (P.H., J.B., M.M.); AstraZeneca Gaithersburg, MD (B.G.K.); Stanford Center for Clinical Research, Stanford University School of Medicine, CA (K.W.M.); Faculty of Medicine and Health, Örebro University, Sweden (L.N.); and Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, UK (F.G.R.F.). schuyler.jones@duke.edu.
Abstract
BACKGROUND: In patients with symptomatic peripheral artery disease with a history of limb revascularization, the optimal antithrombotic regimen for long-term management is unknown. METHODS: The EUCLID trial (Examining Use of Ticagrelor In PAD) randomized 13 885 patients with peripheral artery disease to treatment withticagrelor 90 mg twice daily or clopidogrel 75 mg daily. Patients were enrolled based on an abnormal ankle-brachial index ≤0.80 or a previous lower extremity revascularization. This analysis focuses on the 7875 (57%) patients enrolled based on the previous lower extremity revascularization criterion. Patients could not be enrolled within 30 days of most recent revascularization, and patients with an indication for dual antiplatelet therapy were excluded. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. The primary safety end point was major bleeding. RESULTS:Patients with a previous revascularization had a mean age of 66 years, 73% were male, and the median baseline ankle-brachial index was 0.78. After adjustment for baseline characteristics, patients enrolled based on previous revascularization had similar rates of the primary composite end point (hazard ratio [HR] 1.10, 95% confidence interval [CI] 0.98-1.23, P=0.12) and statistically significantly higher rates of myocardial infarction (HR 1.29, 95% CI 1.08-1.55, P=0.005) and acute limb ischemia (HR 4.23, 95% CI 2.86-6.25, P<0.001) when compared with patients enrolled based on ankle-brachial index criteria. No differences in ticagrelor- versus clopidogrel-treated patients were found for the primary efficacy end point (11.4% vs 11.3%; HR 1.01, 95% CI 0.88-1.15; P=0.90), all-cause mortality (9.2% vs 9.2%; HR 0.99, 95% CI 0.86-1.15; P=0.93), acute limb ischemia (2.5% vs 2.5%; HR 1.03, 95% CI 0.78-1.36; P=0.84), or major bleeding (1.9% vs 1.8%; HR 1.15, 95% CI 0.83-1.59; P=0.41). The median duration of follow-up was ≈30 months. CONCLUSIONS: After adjustment for baseline characteristics, patients enrolled based on previous revascularization for peripheral artery disease had higher rates of myocardial infarction and acute limb ischemia, with similar composite rates of cardiovascular death, myocardial infarction, and stroke when compared with patients enrolled based on the ankle-brachial index criterion. No significant differences were found between ticagrelor and clopidogrel for reduction of cardiovascular or acute limb events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01732822.
RCT Entities:
BACKGROUND: In patients with symptomatic peripheral artery disease with a history of limb revascularization, the optimal antithrombotic regimen for long-term management is unknown. METHODS: The EUCLID trial (Examining Use of Ticagrelor In PAD) randomized 13 885 patients with peripheral artery disease to treatment with ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. Patients were enrolled based on an abnormal ankle-brachial index ≤0.80 or a previous lower extremity revascularization. This analysis focuses on the 7875 (57%) patients enrolled based on the previous lower extremity revascularization criterion. Patients could not be enrolled within 30 days of most recent revascularization, and patients with an indication for dual antiplatelet therapy were excluded. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. The primary safety end point was major bleeding. RESULTS:Patients with a previous revascularization had a mean age of 66 years, 73% were male, and the median baseline ankle-brachial index was 0.78. After adjustment for baseline characteristics, patients enrolled based on previous revascularization had similar rates of the primary composite end point (hazard ratio [HR] 1.10, 95% confidence interval [CI] 0.98-1.23, P=0.12) and statistically significantly higher rates of myocardial infarction (HR 1.29, 95% CI 1.08-1.55, P=0.005) and acute limb ischemia (HR 4.23, 95% CI 2.86-6.25, P<0.001) when compared with patients enrolled based on ankle-brachial index criteria. No differences in ticagrelor- versus clopidogrel-treated patients were found for the primary efficacy end point (11.4% vs 11.3%; HR 1.01, 95% CI 0.88-1.15; P=0.90), all-cause mortality (9.2% vs 9.2%; HR 0.99, 95% CI 0.86-1.15; P=0.93), acute limb ischemia (2.5% vs 2.5%; HR 1.03, 95% CI 0.78-1.36; P=0.84), or major bleeding (1.9% vs 1.8%; HR 1.15, 95% CI 0.83-1.59; P=0.41). The median duration of follow-up was ≈30 months. CONCLUSIONS: After adjustment for baseline characteristics, patients enrolled based on previous revascularization for peripheral artery disease had higher rates of myocardial infarction and acute limb ischemia, with similar composite rates of cardiovascular death, myocardial infarction, and stroke when compared with patients enrolled based on the ankle-brachial index criterion. No significant differences were found between ticagrelor and clopidogrel for reduction of cardiovascular or acute limb events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01732822.
Authors: Michael Szarek; Connie Hess; Manesh R Patel; W Schuyler Jones; Jeffrey S Berger; Iris Baumgartner; Brian Katona; Kenneth W Mahaffey; Lars Norgren; Juuso Blomster; Frank W Rockhold; Judith Hsia; F Gerry R Fowkes; Marc P Bonaca Journal: J Am Heart Assoc Date: 2022-05-27 Impact factor: 6.106
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