title: Vorapaxar and Amyotrophic Lateral Sclerosis: Coincidence or Adverse Association?
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.
  
  
  OBJECTIVE
  To assess the Food and Drug Administration (FDA) reviews on the potential association of vorapaxar with ALS.
  
  
  METHODS
  The review the public FDA records on reported adverse events after vorapaxar.
  
  
  METHODS
  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.
authors.affiliation: 1HeartDrug Research, LLC, Towson, MD;2Johns Hopkins University, Baltimore, MD; and3Clinical Trials Unit, Dong-A University, Busan, Korea.
authors.forename: Victor L
authors.initials: VL
authors.lastname: Serebruany
authors.forename: Seth D
authors.initials: SD
authors.lastname: Fortmann
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hanley
authors.forename: Moo Hyun
authors.initials: MH
authors.lastname: Kim
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology* / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D015994:Incidence; D007783:Lactones / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D044463:Receptor, PAR-1 / Q000378:metabolism; D012307:Risk Factors; D013917:Thrombin / Q000378:metabolism; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D044463:Receptor, PAR-1; D018698:Glutamic Acid; D013917:Thrombin; C530299:vorapaxar