Ticagrelor vs Clopidogrel: CV Events in Peripheral Artery Disease

Peripheral artery disease
Peripheral artery disease
Both ticagrelor and clopidogrel appear to have the same effect on patients with peripheral artery disease.

Results from the EUCLID trial showed that ticagrelor did not reduce incidence of cardiovascular events in patients with peripheral artery disease compared (PAD) with clopidogrel.1,2

The primary efficacy composite end point of cardiovascular death, myocardial infarction (MI), or ischemic stroke occurred in 10.8% of patients in the ticagrelor group compared with 10.6% in the clopidogrel group (hazard ratio [HR]:1.02; 95% CI, 0.92-1.13).1

William R. Hiatt, MD, professor of medicine, division of cardiology at the University of Colorado School of medicine and the study’s principal author, said the trial essentially produced negative results.

“Ticagrelor appears to have the same benefit as clopidogrel,” Dr Hiatt said during a phone interview with Cardiology Advisor. “I think the reason the results are similar is because both drugs are active. This is not a non-inferiority design so we can’t make a claim that ticagrelor retains the benefit of clopidogrel, but it does appear to us that, clinically, that both these drugs are active and equally effective.”

The results were presented at the 2016 American Heart Association Scientific Sessions2 and published simultaneously online by both the New England Journal of Medicine and Circulation.3

At median follow-up of 30 months, researchers found statistically significantly higher rates of MI (HR: 1.29, 95% CI, 1.08-1.55) and acute limb ischemia (HR: 4.23; 95% CI, 2.86-6.25) in the ticagrelor group.

The Examining Use of tiCagreLor In paD (EUCLID) trial included 28 research sites in 11 countries. Patients with PAD were treated with 90 mg twice daily ticagrelor (n=6910) or 75 mg/d clopidogrel (n=6932).

Eligible patients had an ankle-brachial index (ABI) of 0.80 or less or had undergone previous revascularization of the lower limbs.

The only significant difference between the groups was rate of ischemic stroke, which occurred in 1.9% of the patients in the ticagrelor group compared with 2.4% in the clopidogrel group (HR: 0.78; 95% CI, 0.62-0.98; P =.03).

The rate primary safety end point of thrombolysis in MI major bleeding was 1.6% in both groups (HR: 1.10; 95% CI, 0.84-1.43; P =.49).

Researchers observed fewer total fatal bleeding events in the ticagrelor group than (10 vs 20), but significantly more bleeding events leading to discontinuation (168 vs 112; P <.001). Patients in the ticagrelor group were also more likely to stop treatment prematurely (30.1% vs 25.9%; P <.001). Ticagrelor patients were 6 times more likely to develop dyspnea (4.8% vs 0.8%; P <.001) and 1.5 times more likely to experience any bleeding event (2.4% vs 1.6%; P <.001).

Dr Hiatt said the EUCLID steering committee is preparing to publish as many as a dozen additional papers, but these findings suggest that ticagrelor does not have a unique role in treating PAD.

“There are other studies with ticagrelor that are ongoing where additional questions will hopefully be addressed,” said Dr Hiatt. “In terms of [PAD], this result does not show a lead toward benefit. The [Kaplan-Meier] curves are pretty superimposable so it doesn’t look like there is anything uniquely advantageous to ticagrelor in this setting.”


  1. Hiatt WR, Fowkes GR, Heizer, et al; on behalf of the EUCLID Trial Steering Committee and Investigators. Ticagrelor vs clopidogrel in symptomatic peripheral artery disease. N Engl J Med. 2016 Nov 13. doi:10.1056/NEJMoa1611688 [Epub ahead of print].
  2. Patel MR, on behalf of the EUCLID investigators. LCBT.01: Big trials for big questions. Effects of ticagrelor compared with clopidogrel in patients with peripheral artery disease (EUCLID). Presented at: the 2016 American Heart Association Scientific Sessions. November 12-16, 2016; New Orleans, LA.
  3. Jones, WS, Baumgartner I, Hiatt WR, et al; on behalf of the International Steering Committee and Investigators of the EUCLID Trial. Ticagrelor compared with clopidogrel in patients with prior lower extremity revascularization for peripheral artery disease. Circulation. 2016 Nov 13. doi:10.1161/CIRCULATIONAHA.116.025880 [Epub ahead of print].