Ezetimibe was the lipid-lowering agent selected for EWTOPIA because it has an excellent safety record in older patients. There were no important differences between the two study arms in terms of adverse events, according to Dr. Ouchi.
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Dr. June G. Robinson
Discussant Jennifer G. Robinson, MD, said that for a decade she has tried without success to get backing for a primary prevention statin trial in elderly U.S. patients, so congratulations to the Japanese investigators are in order.
She expressed doubts as to the generalizability of the EWTOPIA results to non-Japanese populations, however.
“Frankly, I was very surprised to see the large effect size. EWTOPIA had far more effect than we expected based on other trials of LDL-lowering agents to date,” said Dr. Robinson, professor of epidemiology and medicine and director of the Prevention Intervention Center at the University of Iowa, Iowa City.
“It’s a little better performance than we expected from that magnitude of LDL lowering, which was quite modest,” she added.
Among the possible explanations she cited for the greater magnitude of reduction in major vascular events seen in EWTOPIA as compared, for example, to the IMPROVE-IT trial, which also utilized ezetimibe, are genetic differences in the Japanese population. It’s known that the Japanese have different genetic polymorphisms of Niemann-Pick C1 Like 1 (NPC1L1), which is what ezetimibe binds to in order to inhibit small intestinal enterocyte uptake and absorption of cholesterol. Or it might just be that older adults, regardless of their ethnicity, have a more robust response to LDL lowering than the younger ones who’ve been the focus of previous trials.
“I think the LDL lowering from ezetimibe was very effective in Japanese older adults without cardiovascular disease, and I think that’s a very appropriate therapy for primary prevention moving forward in that population,” Dr. Robinson said.
As for herself, she’s awaiting confirmation in other populations. She’s particularly eager to see the outcome of the ongoing double-blind, randomized STAREE trial of atorvastatin (Lipitor) at 40 mg/day or placebo for primary prevention in 18,000 Australians age 70 and up. Results are expected in 2022.
Dr. Ouchi reported having no financial conflicts regarding the EWTOPIA study, funded by the Japanese government.
SOURCE: Ouchi Y. AHA Late Breaker 02.