Doubts over landmark heart drug trial: ticagrelor PLATO study

Abstract

A top selling antiplatelet drug has never quite shaken off doubts about its advantage over cheaper rivals. With generic versions of ticagrelor about to launch, Peter Doshi takes a fresh look at the evidence Over the past decade the antiplatelet drug ticagrelor (Brilinta in the US and Brilique in Europe) has become firmly established in the treatment of acute coronary syndrome, recommended in guidelines from cardiology societies across the world.123 As the only P2Y12 inhibitor still under patent in the US, the public expenditure is substantial, accounting for around two thirds of the total cost of P2Y12 inhibitors despite less than 10% of total prescriptions.4 In 2022, the US federal government spent more than $750m (£593m; €712m) on ticagrelor. But since its 2011 approval by the US Food and Drug Administration (FDA) doubts have grown about its apparent advantage over cheaper, off patent P2Y12 inhibitors like clopidogrel and prasugrel. While AstraZeneca, ticagrelor’s manufacturer, reported superior efficacy to clopidogrel in the phase 3 trial that brought the drug to market, studies in the post-licensure period have repeatedly reported disappointing results,567891011121314 showing similar efficacy to clopidogrel but with increased bleeding and dyspnoea, prompting calls for a reappraisal of guidelines.1516 With generic versions of ticagrelor expected soon in the US, The BMJ took a fresh look at the evidence. Our investigation found AstraZeneca’s drug was approved over the emphatic objections of FDA scientific review staff, and that ticagrelor’s major clinical trial, named PLATO, was the focus of a long and rancorous dispute over its basic reliability. The BMJ can also disclose new details on the controversy after obtaining primary PLATO trial records and unpublished data through a freedom of information request that shows further problems in data …