A Randomized, Pharmacodynamic Comparison of Low Dose Ticagrelor to Clopidogrel in Patients With Prior Myocardial Infarction

Overview

Taken together the results from CHARISMA and PEGASUS-TIMI54, it appears that physicians may consider extending beyond 1 year or reinitiating treatment with clopidogrel 75 mg od or ticagrelor 60mg bid in patients with a prior MI and features of high ischemic and low bleeding risk. Comparative clinical or pharmacodynamic studies, however, between clopidogrel 75 mg od and ticagrelor 60 mg bid in the chronic phase of stable post MI patients have not been performed. In a platelet substudy of PEGASUS-TIMI 54, 180 patients who had received \>4 weeks of study medication had platelet reactivity assessment. Ticagrelor 60mg bid achieved high levels of peak and trough platelet inhibition in nearly all patients, with similar consistency of effect compared to 90mg bid. Platelet reactivity (PRU) was significantly reduced with ticagrelor 60mg bid compared to placebo. In light of this, we believe that a dedicated pharmacodynamic study of ticagrelor 60 bid mg vs clopidogrel 75 mg od in a PEGASUS-like population would be informative for the practicing clinician, thus setting the rationale for conducting this specifically designed investigation. This is a prospective, randomized, single blind, single center, crossover study. Eligible patients undergoing P2Y12 receptor antagonist therapy before screening will undergo a 14-day minimum washout period before randomization. Following screening/washout period (visit 1), patients will be randomized (visit 2, time 0) in 1:1 fashion to either clopidogrel 75 mg od or ticagrelor 60 mg bid. Following 14±2 days (visit 3) patients will receive alternate treatment for additional 14 days (visit 4). Platelet reactivity assessment will be performed with the VerifyNow P2Y12 reaction assay at time 0, prior to first study drug dose. At visit 3 platelet function will be assessed at 2-4 hours post dose and prior to crossover. At visit 4 also platelet function will be assessed at 2-4 hours post study drug post dose. All patients will receive concomitant aspirin (100 mg/d) and standard secondary prevention medication. The primary endpoint is the platelet reactivity measured in P2Y12 reaction units (PRU) at the end of the 2 study periods (pre-crossover and post-crossover).