Vorapaxar and Amyotrophic Lateral Sclerosis: Coincidence or Adverse Association?

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.

To assess the Food and Drug Administration (FDA) reviews on the potential association of vorapaxar with ALS.

The review the public FDA records on reported adverse events after vorapaxar.

Incidence of ALS after vorapaxar and placebo.

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.

Potential adverse association of vorapaxar with ALS risks may be related to off-target neuronal PAR receptor(s) blockade beyond platelet inhibition.