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.

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.

• Authors: Victor L Serebruany, Seth D Fortmann, Daniel F Hanley, Moo Hyun Kim
• Journal: American journal of therapeutics (Am J Ther) 2017 Mar/Apr Vol. 24 Issue 2 Pg. e139-e143 ISSN: 1536-3686 [Electronic] United States
• PMID: 28267691 (Publication Type: Journal Article, Review)

Chemical References

• Lactones
• Platelet Aggregation Inhibitors
• Pyridines
• Receptor, PAR-1
• Glutamic Acid
• Thrombin
• vorapaxar

Topics

• Amyotrophic Lateral Sclerosis (epidemiology, metabolism)
• Glutamic Acid (metabolism)
• Humans
• Incidence
• Lactones (therapeutic use)
• Platelet Aggregation Inhibitors (therapeutic use)
• Pyridines (therapeutic use)
• Receptor, PAR-1 (antagonists & inhibitors, metabolism)
• Risk Factors
• Thrombin (metabolism)
• United States
• United States Food and Drug Administration