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[DOI] [PMC free article] [PubMed] [Google Scholar] 63.Dorion S., Jeukens J., Matton D.P., Rivoal J

Experiments ex vivo have shown that vinpocetine acts as a selective inhibitor of Ca 2+ /calmodulin-dependent cyclic nucleotide phosphodiesterase type I [21,108], a potent blocker of voltage-gated sodium channels [109,110], inhibits platelet aggregation, reduces blood viscosity, vasodilates cerebral arteries, and increases cerebral blood flow [111]

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While Alnylams Phase III APOLLO-B study hit both key primary and secondary endpoints, the FDA stated in the documents that the effects of patisiran compared to placebo on both endpoints were small, of questionable clinical meaningfulness, and may not be detectable by patients. Major discussion points during the adcomm meeting included whether these key endpoints were appropriate to ascertain clinical meaningfulness in the ATTR-CM population, and panelists expressed varying opinions on whether the magnitude of the benefit seen in trial data was clinically meaningful