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EUCLID: Ticagrelor not superior to clopidogrel for CV event reduction in patients with PAD
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NEW ORLEANS — Ticagrelor was not shown to be superior for reducing CV events in patients with symptomatic peripheral artery disease, according to a presentation at the American Heart Association Scientific Sessions.
Previous data suggested that clopidogrel monotherapy conferred lower CV risk for patients with PAD than a regimen of aspirin. Manesh R. Patel, MD, and colleagues conducted the EUCLID study to compare the effects of clopidogrel with ticagrelor (Brilinta, AstraZeneca) in that population.
“Peripheral artery disease is considered a systematic manifestation of atherosclerosis which affects over 200 million people worldwide and is associated with both CV and limb morbidity and mortality,” Patel, associate professor of medicine, chief of the division of cardiology and chief of the division of clinical pharmacology at Duke Clinical Research Institute, Duke University School of Medicine, said during a press conference. “… Antiplatelet therapy is recommended for all patients with PAD.”
The double blind, event-driven trial was conducted at 811 sites in 28 countries. A total of 13,885 patients with symptomatic PAD (median age, 66 years; 72% men) were randomly assigned to receive monotherapy with ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily.
Eligible patients had an ankle-brachial index of 0.8 or less (43%) or had a history of lower-limb revascularization (57%).
The primary efficacy endpoint was a composite of adjudicated CV death, MI or ischemic stroke. The primary safety endpoint was major bleeding. Median follow-up was 30 months.
The primary efficacy endpoint occurred in 12.5% of patients receiving ticagrelor (n = 751) and in 12.5% (n = 740) of those assigned clopidogrel (HR = 1.02; 95% CI, 0.92-1.13; P = .65).
There was no difference between the groups in CV death or MI, but those assigned ticagrelor had a lower risk for ischemic stroke (1.9% vs. 2.4%; HR = 0.78; 95% CI, 0.68-0.98; P = .03), Patel reported here.
Acute limb ischemia occurred in 1.7% of the patients in each group (HR = 1.03; 95% CI, 0.79-1.33; P = .85) and major bleeding occurred in 1.6% of patients in each group (HR = 1.1; 95% CI, 0.84-1.43; P = .49), according to the results.
During a discussion of the trial, Cardiology Today Chief Medical Editor Carl J. Pepine, MD, MACC, eminent scholar emeritus and professor in the division of cardiovascular medicine at University of Florida, Gainesville, acknowledged that knowledge gaps in the treatment of PAD remain.
“How were [the] EUCLID investigators able to achieve results with clopidogrel that look like ticagrelor? This is important since ticagrelor was shown superior for prevention of the same atherosclerosis adverse outcomes (death, MI, stroke) in the ACS trial PLATO,” he said. “One possible contribution was that they prospectively did not enroll patients with genotypes known to be associated with poor responses to clopidogrel. Additionally, about 300 patients discontinued ticagrelor due to dyspnea. So these patients did not receive the benefit of ticagrelor. Clearly, other unknown factors likely contributed.”
Pepine called for “more studies like EUCLID to determine the optimal antiplatelet therapy to prevent CV and limb-related events, additional medical therapies, particularly biologics, for claudication, and the role of dietary intervention, in addition to statins and other drugs, to prevent and modify PAD,” Pepine said. – by Dave Quaile
References:
Patel MR, et al. LBCT.01 – Big Trials for Big Questions. Presented at: American Heart Association Scientific Sessions; Nov. 12-16, 2016; New Orleans.
Hiatt WR, et al. N Engl J Med. 2016;doi:10.1056/NEJMoa1611688.
Disclosure: The study was funded by AstraZeneca. Patel reports receiving research support from AstraZeneca, CSL Behring, HeartFlow, Janssen Research & Development, Johnson & Johnson, Maquet and Medtronic; and consulting/serving on an advisory board for AstraZeneca, Bayer, CSL Behring, Genzyme, Janssen Research & Development, Medtronic and Merck. Pepine reports no relevant financial disclosures.
Perspective
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Heather Gornik, MD
Ticagrelor did not improve CV outcomes or limb outcomes in PAD patients compared to clopidogrel. While the results are disappointing, in the sense that there are dearth of medical therapies for PAD, the study was very well done. I only wished there were an aspirin therapy arm, as that would have helped us answered a key question in PAD regarding the relative efficacy of aspirin vs. clopidogrel or ticagrelor in treatment of PAD.
The most amazing thing about the study is that more than 13,000 patients enrolled, and all patients were specifically included on the basis of PAD. This is truly the first PAD CV outcome megatrial. I hope big pharma takes notice that there is an interest in studying new medical therapies for PAD, and an ability to successfully recruit these patients for participation.
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