The platelet function substudy of the TRILOGY-ACS trial shows that there is no significant difference between prasugrel and clopidogrel in cardiovascular (CV) mortality, myocardial infarction (MI), or stroke outcomes.
Moreover, there was no significant association between platelet reactivity and ischemic outcomes, say the researchers, who believe that their findings explain the result of the overall TRILOGY-ACS study.
The initial study results showed that prasugrel was not superior to clopidogrel in reducing recurrent CV events in medically managed patients with acute coronary syndrome who did not undergo revascularization.
In the current substudy, which included 28% (n=2564) of the patients from the overall trial, Matthew Roe (Duke Clinical Research Institute, Durham, North Carolina, USA) and team measured on-treatment reactivity at baseline and at 2 hours, as well as at 1, 3, 6, 12, 18, 24, and 30 months after randomization.
They used the VerifyNow P2Y12 test, which was previously shown to measure the P2Y12 effect of clopidogrel and prasugrel and correlated with active metabolite exposure of both drugs.
The findings revealed that at 30 days the median P2Y12 reaction unit (PRU) levels among participants younger than 75 years and weighing 60 kg or more were 64 in the prasugrel group versus 200 in the clopidogrel group, a significant difference that persisted through all timepoints.
The median 30-day PRU levels in participants younger than 75 years and weighing less than 60 kg were 139 for the prasugrel group compared with 209 in the clopidogrel group, and for those aged 75 years or over, were 164 in the prasugrel group versus 222 for the clopidogrel group.
At 30 months, the rate of the primary efficacy endpoint of CV mortality, MI, or stroke was 17.2% in the prasugrel group and 18.9% in the clopidogrel group, a nonsignificant difference.
The authors note that there were also no significant differences in the continuous distribution of 30-day PRU values for participants who experienced a primary efficacy endpoint after 30 days compared with those who did not experience an event, and no significant association between the occurrence of the primary efficacy endpoint and continuous PRU values.
They also observed similar findings with 30-day PRU cutpoints used to define high on-treatment platelet reactivity - including a PRU of more than 208 and a PRU of more than 230.
"The TRILOGY-ACS platelet function substudy provides several findings that may explain the overall trial results, which demonstrated no significant difference in ischemic outcomes through the first 12 months despite clinical observations of greater P2Y12 inhibition with prasugrel than with clopidogrel," write the authors in JAMA.
Editorialist Matthew Price (Scripps Translational Research Institute, La Jolla, California, USA) comments: "Systematic blood sample collection should be considered in randomized clinical trials designed to evaluate novel therapeutics or to expand product labeling.
"This might permit pharmacodynamic or exploratory pharmacogenomic analyses by independent groups that might be useful in identifying individuals who may safely derive the greatest treatment benefit."
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