Vorapaxar and amyotrophic lateral sclerosis: Coincidence or adverse association?

Victor L. Serebruany, Seth D. Fortmann, Daniel F Hanley, Moo Hyun Kim

Research output: Contribution to journalArticle

Abstract

Background: Vorapaxar, a novel antiplatelet thrombin PAR-1 inhibitor, is currently approved for post myocardial infarction and peripheral artery disease indications with concomitant use of clopidogrel and/or aspirin. The vorapaxar safety profile was acceptable. However, aside from heightened bleeding risks, excesses of solid cancers and diplopia, there were more amyotrophic lateral sclerosis (ALS) diagnoses after vorapaxar. Study Question: To assess the Food and Drug Administration (FDA) reviews on the potential association of vorapaxar with ALS. Study Design: The review the public FDA records on reported adverse events after vorapaxar. Measures and Outcomes: Incidence of ALS after vorapaxar and placebo. Results: The ALS risk appears very small, about 1 case per 10,000 treated subjects, but quite probable. Indeed, there were overall 2 placebo and 4 vorapaxar ALS incidences in the Phase III clinical trials. Conclusions: Potential adverse association of vorapaxar with ALS risks may be related to off-target neuronal PAR receptor(s) blockade beyond platelet inhibition.

Original languageEnglish (US)
Pages (from-to)e139-e143
JournalAmerican Journal of Therapeutics
Volume24
Issue number2
DOIs
StatePublished - 2017

Fingerprint

Amyotrophic Lateral Sclerosis
clopidogrel
United States Food and Drug Administration
Placebos
Phase III Clinical Trials
Diplopia
vorapaxar
Peripheral Arterial Disease
Incidence
Thrombin
Aspirin
Blood Platelets
Myocardial Infarction
Outcome Assessment (Health Care)
Hemorrhage
Safety

Keywords

  • Adverse events
  • Amyotrophic lateral sclerosis
  • Clinical trials
  • Glutamate
  • PAR receptors
  • Safety
  • Thrombin
  • Vorapaxar

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Vorapaxar and amyotrophic lateral sclerosis : Coincidence or adverse association? / Serebruany, Victor L.; Fortmann, Seth D.; Hanley, Daniel F; Kim, Moo Hyun.

In: American Journal of Therapeutics, Vol. 24, No. 2, 2017, p. e139-e143.

Research output: Contribution to journalArticle

Serebruany, Victor L. ; Fortmann, Seth D. ; Hanley, Daniel F ; Kim, Moo Hyun. / Vorapaxar and amyotrophic lateral sclerosis : Coincidence or adverse association?. In: American Journal of Therapeutics. 2017 ; Vol. 24, No. 2. pp. e139-e143.
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