Misrepresentation of vital status follow-up: challenging the integrity of the PLATO trial and the claimed mortality benefit of ticagrelor versus clopidogrel

Abstract

Context: Ticagrelor, a novel, reversible, and oral P2Y12 receptor antagonist, was claimed to reduce all-cause mortality compared to clopidogrel in the PLATO trial.

Objective: We sought to ascertain vital status follow-up for clopidogrel and ticagrelor to determine if any discrepancy existed by reviewing data from the FDA Complete Response Review.

Results: The FDA Complete Response Review indicated misrepresentation of vital status follow-up by the sponsor's presenter at the Cardiovascular and Renal Drugs Advisory Committee. Instead of five patients with missing vital status follow-up, the FDA primary efficacy reviewer indicated that there was a minimum of 106 patients. Additionally and more concerning was the fact that significantly more patients on ticagrelor (3.1%, n = 289 patients) had incomplete vital status follow-up versus clopidogrel (2.6%, n = 242 patients, p = 0.04 for the difference).

Conclusions: The Advisory Committee that voted in favor to approve ticagrelor was given misrepresented data, which may have affected the approval of ticagrelor. The fact that significantly more patients on ticagrelor had incomplete vital status follow-up versus clopidogrel challenges the claimed mortality benefit of ticagrelor and the approval of the PLATO trial.

Keywords: Clopidogrel; Misrepresentations; Ticagrelor.