Dr. Sabatine agreed. While neurocognitive events in OSLER were self-reported by patients, FOURIER includes a substudy featuring formal neurocognitive testing using validated instruments. And while that should provide definitive answers, he said he’s not too concerned about the neurocognitive issue.
“Biologically, LDL cholesterol is not used as a source of cholesterol for cells, and that’s especially true for cells in the CNS because of the blood-brain barrier. And very low LDL levels don’t appear to have any effect on the CNS in animal models,” he said.
A more comprehensive picture of evolucumab’s safety was provided elsewhere at ACC 15 by Dr. Peter P. Toth. His safety analysis incorporated more than 6,000 evolucumab-treated patients and 3,569 controls who participated in a dozen phase II and III trials as well as OSLER.
The short version: This pooled analysis demonstrated no increase in any clinical adverse events or laboratory abnormalities with evolocumab, compared with controls. That includes muscle-related adverse events, liver or renal toxicity, impairment in glucose metabolism, infections, injection-site reactions, and neurocognitive events, said Dr. Toth of the University of Illinois, Peoria.
Simultaneous with Dr. Sabatine’s presentation at ACC 15, the OSLER results were published online (N. Engl. J. Med. 2015 [doi: 10.1056/NEJMoa1500858]).
Both OSLER and Dr. Toth’s broader safety analysis were funded by Amgen. Dr. Sabatine and Dr. Toth reported having received research grant support from and serving as consultants to Amgen and numerous other pharmaceutical companies. Dr. Hochman is a consultant to GlaxoSmithKline. Dr. Cannon has received research grant support from and served as a consultant or advisor to many pharmaceutical companies.