SOURCE: Hiatt WR, Fowkes FG, Heizer G, et al. Ticagrelor versus clopidogrel in symptomatic peripheral artery disease. N Engl J Med 2017;376:32-40.

Clopidogrel has demonstrated superiority to aspirin for reducing cardiovascular events in patients with stable vascular disease (i.e., post-myocardial infarction, post-stroke, prevalent peripheral arterial disease). In the CAPRIE trial, patients on clopidogrel experienced an almost 9% lower relative risk of cardiovascular events than patients on aspirin, although the absolute risk reduction was very small (0.5%). At the time of publication of the CAPRIE trial, this presented a dilemma for clinicians, primarily because of cost issues.

Ticagrelor is in the same class of agents as clopidogrel: Both are P2Y12 inhibitors, which lead to reduced platelet aggregation. The success that ticagrelor has achieved in acute coronary syndromes prompted the question of whether ticagrelor might provide greater reduction in cardiovascular events than clopidogrel, since the presence of peripheral arterial disease (whether symptomatic or not) is indicative of coexisting coronary artery disease.

Hiatt et al conducted a randomized, double-blind, placebo-controlled trial of ticagrelor vs. clopidogrel in patients with peripheral arterial disease (n = 13,885). The primary outcome was incident cardiovascular events over 2.5 years.

There was no statistically significant difference in cardiovascular outcomes between the two agents. The additional expense of ticagrelor, plus the fact that it is administered b.i.d in contrast to the q.d. dosing of clopidogrel, suggest that clopidogrel should remain the preferred agent.