Clopidogrel Holds Advantage in Older NTSE ACS Patients: POPular AGE Published

Older patients presenting to hospital with non-ST-elevation ACS fare better when treated with the less-potent antiplatelet agent clopidogrel, specifically with respect to major and minor bleeding, as compared to treatment with ticagrelor, the POPular AGE study shows.

Presented at the European Society of Cardiology (ESC) 2019 Congress, the study was published April 25, 2020, in the Lancet. As the investigators stated last year, the key message is that clopidogrel represents a second option to use in the treatment of NSTE ACS. The optimal P2Y12 inhibitor used as part of dual antiplatelet therapy should be made on a patient-by-patient basis, they say.

“We try to tailor therapy based on the previous history of the patient,” senior investigator Jurriën ten Berg, MD, PhD (St. Antonius Hospital, Nieuwegein, the Netherlands), told TCTMD. “If they have any reason for a higher bleeding risk, whether this is a previous bleed, hypertension, or renal insufficiency, we switch to clopidogrel. For the ones who are not frail—older than 70 years but still quite ‘young’—then we’ll still treat them with ticagrelor.”

As reported by TCTMD when POPular AGE was presented during the ESC late-breaking science session, the study included 1,002 patients 70 years or older randomly assigned to treatment with clopidogrel or ticagrelor (prasugrel was an option, but just 2% of patients received that drug). The primary endpoint of PLATO major and minor bleeding was significantly lower in the clopidogrel arm, a benefit that was not offset by an increase in ischemic events. The net clinical benefit outcome of all-cause death, MI, stroke, and PLATO minor/major bleeding favored the clopidogrel treatment arm.

In an editorial, Peter Sinnaeve, MD, PhD (University Hospitals, Leuven, Belgium), and Sofie Gevaert, MD, PhD (Ghent University Hospital, Belgium), praise the investigators for the trial given that older patients are tougher to recruit, are harder to retain, and often have low adherence rates.

Despite the findings, Sinnaeve and Gevaerts say they believe there are still more dual antiplatelet therapy trials to potentially be performed in ageing patients, noting that a planned short course of dual treatment with any P2Y12 inhibitor might be preferred in frail, elderly patients, especially in this era of improved drug-eluting stents. Another option to be tested might include a short treatment period with ticagrelor or prasugrel followed by a switch to clopidogrel. Even testing a lower maintenance dose of ticagrelor—60 mg instead of the 90-mg twice daily dose used in POPular AGE—would be worth studying, say the editorialists.

Still, the trial supports a “less is more” approach with clopidogrel in very old, or frail patients with NSTE ACS, while ticagrelor or prasugrel remain appropriate for all other patients with ACS, they say.

The superiority of ticagrelor over clopidogrel in ACS patients was established in PLATO, while the TRITON-TIMI 38 study showed that ACS patients treated with prasugrel had a lower risk of ischemic events, but more bleeding, when compared with clopidogrel.