TRILOGY: Prasugrel, Clopidogrel Look Similar in ACS Patients

The results from TRILOGY ACS clearly showed no overall advantage for treating acute coronary syndrome patients who are managed medically with prasugrel compared with clopidogrel for the study’s primary outcome. The efficacy results showed two very interesting advantages to prasugrel treatment: a statistically significant reduction in recurrent ischemic coronary events, and a statistically significant reduction in events starting a year after the onset of treatment. The recurrent-event analysis was prespecified, and is a very clinically relevant endpoint; the 1-year landmark analysis was done post hoc. Because the primary end point showed no significant benefit, both of these other outcomes must be considered just hypothesis generating.

The safety results for prasugrel were very reassuring. They indicated that barring patients with a history of stroke from the trial and using a reduced, 5 mg/day dosage for patients aged 75 or older and for patients who weighed less than 60 kg eliminated the excess risk for major bleeding events compared with clopidogrel, which were seen in the prior comparison of prasugrel and clopidogrel, the TRITON-TIMI 38 study.

In the United States clopidogrel is now available as a generic drug and is substantially cheaper than prasugrel. If cost were not an issue, then I might be inclined to use prasugrel over clopidogrel in the types of patients enrolled in TRILOGY ACS because of the signals of possible superior efficacy and no added safety risk. But cost is an issue and will remain so for several more years until prasugrel goes off patent. Until then, the possible advantages of prasugrel over clopidogrel do not tip the balance compared with prasugrel’s excess expense.

But the issue of which drug to choose in these patients doesn’t end there, because there is a third option, ticagrelor. A prespecified sub-analysis of the PLATO trial, which compared ticagrelor with clopidogrel in acute coronary syndrome patients, looked at the comparison between the two drugs specifically in patients with non–ST-segment elevation acute coronary syndrome who did not initially undergo invasive management. This is a population of patients very similar to those enrolled into TRILOGY ACS. The subanalysis showed that ticagrelor had a significant efficacy advantage over clopidogrel that was similar to what was seen in the entire PLATO trial, and that provides a compelling reason to consider ticagrelor over clopidogrel in these patients.

But the overall PLATO results as well as this subanalysis also showed a statistically significant excess risk for major bleeding events for ticagrelor, compared with clopidogrel. And ticagrelor, like prasugrel, is substantially more expensive than clopidogrel.

A further complication is that ticagrelor is a twice-daily drug, while clopidogrel and prasugrel are administered once daily.

If I were treating the TRILOGY ACS type of patients, cost were no object, the patients seemed likely to be compliant with their drug regimen, and their bleeding risk was relatively low, then I might want to go with ticagrelor to take advantage of its efficacy edge over clopidogrel. But if cost were a significant consideration, or I had doubts about regular patient compliance with a b.i.d. regimen, or the patient had a high risk for bleeding complications, then clopidogrel might seem like the most attractive option.

DEEPAK L. BHATT, M.D., is chief of cardiology at the VA Boston Healthcare System. Dr. Bhatt served as a coinvestigator and a member of the steering committee for TRILOGY ACS. He said that he has received grant support from several drug companies, but not from the companies that sponsored TRILOGY ACS. Dr. Bhatt made these comments in an interview.