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POPular AGE: Clopidogrel remains an option for elderly with ACS
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PARIS — New data from the POPular AGE study support the use of clopidogrel over ticagrelor and prasugrel, based on significant reduction in bleeding, in patients aged 70 years and older with non-ST-elevation ACS.
While the newer, more potent P2Y12 inhibitors have a role in ACS, bleeding remains a risk, the researchers concluded.
In this elderly-only population in POPular AGE, the co-primary endpoint of PLATO major and minor bleeding was higher among those older than 70 who received ticagrelor (Brilinta, AstraZeneca) or prasugrel (Effient, Daiichi Sankyo/Eli Lilly). The event rate was 23.1% in the ticagrelor/prasugrel group vs. 17.6% in the clopidogrel group (HR = 0.74; 95% CI, 0.56-0.97), showing superiority of clopidogrel in reducing bleeding, according to Marieke E. Gimbel, MD, from St. Antonius Hospital, Nieuwegein, the Netherlands.
The other co-primary endpoint, net clinical benefit, defined as death, MI, stroke, and PLATO major and minor bleeding, occurred in 30.7% of patients assigned ticagrelor or prasugrel vs. 27.3% assigned clopidogrel (absolute risk difference, –3.4%; 95% CI, –9 to 2.3). The P value was .06, which just missed significance to provide noninferiority, Gimbel said. She noted however, that this finding “might change when we complete the 100% follow-up of the last patients,” which is expected in October. At the time of presentation, the researchers reported follow-up data on 99.6% of participants.
“Until now, it [has been] unclear what the optimal antiplatelet treatment is in the elderly population,” Gimbel said.
The randomized, open-label POPular AGE trial enrolled an all-comers population of 1,003 patients with NSTEACS aged 70 years and older admitted to 11 hospitals in the Netherlands from 2013 to 2018. Mean age was 77 years and nearly two-thirds were men. During the hospital stay, about 90% of patients underwent coronary angiography, generally via radial access. Of those, approximately 50% underwent PCI and 16% underwent CABG.
In total, 501 elderly patients received clopidogrel and 502 received ticagrelor or prasugrel. The choice between ticagrelor or prasugrel was made according to local protocol. Ticagrelor was the drug of choice in 93.8% of the ticagrelor/prasugrel group.
Gimbel also noted that the researchers observed a benefit of clopidogrel in secondary safety outcomes. PLATO major bleeding (8% vs. 4.4%; P = .02), intracranial bleeding (1% vs. 0.4%; P = .26) and fatal bleeding (1% vs. 0%; P = .03) were all higher with ticagrelor and prasugrel, compared with clopidogrel, according to the results.
The secondary efficacy outcome of death, MI and stroke was similar between the ticagrelor/prasugrel and clopidogrel groups (clopidogrel, 12.8%; ticagrelor/prasugrel, 12.5%; HR = 1.02; 95% CI, 0.72-1.45).
Subgroup analyses performed were consistent with the main results, Gimbel said.
Nonadherence was an issue in this trial, Gimbel noted. Overall, adherence was 76% in the clopidogrel group and 51% in the ticagrelor or prasugrel group. The primary reasons for switching or discontinuation in the ticagrelor/prasugrel group were bleeding, novel oral anticoagulant prescription and dyspnea.
The choice to study the optimal antiplatelet agent in older adults is related to the underrepresentation of the elderly in randomized clinical trials, Gimbel said. Two large trials in this area, TRITON-TIMI 38 and PLATO, enrolled a low percentage of elderly patients. In TRITON-TIMI 38, a comparison of prasugrel vs. clopidogrel for ACS, just 13% of participants were 75 years and older, and in PLATO, which evaluated ticagrelor vs. clopidogrel, just 15% were 75 and older. Moreover, registry data show that approximately 35% of the non-STEMI population is aged 75 years and older.
Taken together, “compared to ticagrelor or prasugrel in the POPular AGE trial, we conclude that clopidogrel significantly reduced bleeding and was similar in preventing thrombotic events. Therefore, we conclude clopidogrel is the preferred choice in patients 70 years and older with NSTEACS,” Gimbel said. – by Katie Kalvaitis
Reference:
Gimbel ME, et al. Late Breaking Science in Acute Coronary Syndromes 1. Presented at: European Society of Cardiology Congress; Aug. 31-Sept. 4, 2019; Paris.
Disclosure: Gimbel reports no relevant financial disclosures.