The PLATO trial - was it too good to be true?

Abstract

The PLATO trial was the sole reason Ticagrelor was established in the US, reporting a 16% reduction in cardiovascular death, myocardial infarction and strokes across 18,624 patients in 43 countries. However, methodological concerns- including regional discrepancies, independent monitoring inconsistencies, and data irregularities- raise questions about its validity. Notably, North American patients experienced worse outcomes with ticagrelor, and subsequent trials failed to replicate PLATO’s benefits. A 2025 meta-analysis showed pooled ticagrelor effects are largely driven by PLATO, suggesting guideline recommendations may require reevaluation. Future meta-analyses may benefit from excluding this trial from their selection.