Prasugrel Versus Ticagrelor
Authors: Marc P. Bonaca, Stephen D. Wiviott
Journal: Circulation (2016)

ead-to-head comparison of currently available therapies remains a significant challenge.As newer generation agents are developed, they are each compared against the prior standard of care to prove either superiority or noninferiority; however, they are rarely compared against each other.Cross-trial comparisons of efficacy and safety are fraught with hazard and should be interpreted with caution even when using the same control.Differences in trial design and conduct, management of control therapy, sample size and statistical power, and a host of other factors unrelated to the experimental therapy may influence each trial's observed efficacy and safety.Although the availability of multiple therapeutic options for a given condition has advantages over a single agent, understanding whether 1 agent has superior efficacy and/or safety may be useful particularly when there are differences in cost, availability, or tolerability.Within this context, the PRAGUE-18 trial (Prasugrel versus Ticagrelor in Patients with Acute Myocardial Infarction Treated with Primary Percutaneous Coronary Intervention) investigators should be congratulated for their effort to compare the efficacy of the 2 currently available potent P2Y 12 antagonists that are favored for use in patients presenting with acute coronary syndromes. 1Both prasugrel and ticagrelor have been shown to be superior to clopidogrel in patients with acute coronary syndromes for reducing ischemic risk, but with increased bleeding, and have class I guideline recommendations in the United States and Europe. 2,3From the pivotal trials, including TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction 38) for prasugrel and PLATO (Study of Platelet Inhibition and Patient Outcomes) for ticagrelor, many have pointed to apparent differences in their observed efficacy and safety relative to clopidogrel, including the magnitude of efficacy, specific component end points reduced, safety, and tolerability.These observed differences may be explained in part by trial designs; however, because these agents also represent different drug classes with different mechanisms of action at the P2Y 12 receptor, it is also possible that they have different therapeutic profiles.Without a rigorous head-to-head comparison, clinicians are forced to choose based on a variety of factors, including subgroup findings, cost, and availability.As reported in this issue of Circulation, the PRAGUE-18 trial concept, therefore, held the promise to provide a rigorous dataset to support clinician decision making in the acute coronary syndrome setting. 4RAGUE-18 was designed to follow 2500 subjects with acute myocardial infarction for 1 year. 4The trial, as described in the appendix, was initially designed to test the hypothesis that ticagrelor would be superior to prasugrel for reducing the composite of cardiovascular death, myocardial infarction, or stroke at 30 days, an outcome described as a key secondary end point in the final manuscript resulting from an end point change.A total of 1230 patients were randomized in an Prasugrel Versus ticagrelor Uncertainty remains