1. In patients with peripheral arterial disease (PAD), there were no significant differences between ticagrelor and clopidogrel therapy in terms of the risk of cardiovascular death, myocardial infarction (MI), or ischemic stroke.
2. A similar percentage of patients in each group developed acute limb ischemia and major bleeding.
Evidence Rating: 1 (Excellent)
Study Rundown: Systemic atherosclerosis can manifest in patients as PAD. Patients with PAD are at a higher risk of ischemic stroke, MI, and cardiovascular death. Clopidogrel has been shown to be superior to aspirin in reducing cardiovascular events. Ticagrelor, an inhibitor of platelet P2Y12 receptor, has been shown to be effective for patients with acute coronary syndromes and stable coronary artery disease. The Examining Use of Ticagrelor in Peripheral Artery Disease (EUCLID) trial examined whether monotherapy with ticagrelor would be superior to clopidogrel in preventing cardiovascular death, MI, or ischemic stroke in patients with known PAD.
Ticagrelor and clopidogrel were found to be similar in preventing cardiovascular death, MI, and ischemic stroke. The percentage of patients who developed acute limb ischemia and major bleeding were similar between the two groups. Due to side effects, such as dyspnea and minor bleeding, ticagrelor was discontinued more frequently compared to clopidogrel.
Relevant Reading: Ticagrelor versus clopidogrel in patients with acute coronary syndromes.
In-Depth [randomized controlled trial]: This was a double-blind, event-driven trial that randomly assigned 13 885 patients with PAD in a 1:1 ratio to receive either clopidogrel (75 mg once daily) or ticagrelor (90 mg twice daily). Patient were included in the study if they met one of the two inclusion criteria: 1) prior revascularization of the lower limbs for symptomatic disease that occurred more than 30 days prior to randomization or 2) hemodynamic evidence of PAD demonstrated by ABI of 0.8 or less at screening. The primary efficacy endpoint was the first occurrence of an MI, ischemic stroke, or cardiovascular death and secondary endpoint included the primary endpoint plus acute limb ischemia leading to hospitalization – this was tested in a hierarchical fashion. The primary safety endpoint included major bleeding based on TIMI criteria.
The results demonstrated that there was no significant difference in the primary efficacy endpoint. An overall 10.8% of the ticagrelor group and 10.6% receiving clopidogrel developed the primary efficacy endpoint (HR 1.02; 95%CI, 0.92 to 1.13; p = 0.65). Acute limb ischemia occurred in 1.7% of the patients from each group (HR 1.03; 95%CI, 0.79 to 1.33; p = 0.85). Major bleeding occurred in 1.6% of the patients with there being no significant difference between the groups (HR 1.10; 95%CI, 0.84 to 1.43; p = 0.49). Dyspnea occurred at a significantly higher rate in the ticagrelor group compared to the clopidogrel group (4.8% vs. 0.8%, p < 0.001). Also, any bleeding occurred at a significantly higher rate in the ticagrelor group compared to the clopidogrel group (2.4% vs. 1.6%, p < 0.001).
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