Clopidogrel versus ticagrelor or prasugrel in patients aged 70 years or older with non-ST-elevation acute coronary syndrome (POPular AGE): the randomised, open-label, non-inferiority trial

In this RCT (n=1002), clopidogrel was non-inferior to ticagrelor for net clinical benefit (28% v 32%; absolute difference -4%; 95% CI -10.0 to 1.4; p=0.03 for non-inferiority) and superior for the primary bleeding outcome (18% v 24%, HR 0.71; 0.54-0.94; p=0.02 for superiority).

SPS commentary:

Although the comparator arm was initially supposed to be treatment with one of the more potent P2Y12 inhibitors ticagrelor or prasugrel, the majority (95%) received ticagrelor and so the comparison presented is clopidogrel versus ticagrelor.

There were two primary endpoints to this study. The first was any bleeding requiring medical intervention (PLATelet inhibition and patient Outcomes [PLATO] major or minor bleeding). The reduction in bleeding risk with clopidogrel was driven by a reduction in both minor and major bleeds. The second was net clinical benefit (all-cause death, myocardial infarction, stroke, PLATO major and minor bleeding) and the non-inferiority margin was set at 2%. Although there were five stent thromboses in the clopidogrel arm (none with ticagrelor), there were no differences in myocardial infarction or cardiovascular death.

Based on their results, the authors suggest that clopidogrel is a favourable alternative to ticagrelor in patients aged 70 years and above presenting with non-ST elevation ACS, as it was associated with fewer bleeding episodes without an increase in the combined clinical benefit endpoint.

A related Comment notes that the study was underpowered for ischaemic events, and early discontinuation or switching was higher with ticagrelor, likely reflecting both a higher frequency of side-effects and a preference for shorter dual antiplatelet therapy in those at an increased risk of bleeding. They suggest that this does not answer the question about what the most appropriate dual antiplatelet therapy is for older patients, as several other options (e.g. a short dual antiplatelet regimen; planned de-escalation to clopidogrel after a short initial treatment with ticagrelor or prasugrel; a lower maintenance dose of ticagrelor or prasugrel) need to be explored.


The Lancet

Resource links: