Doubts over landmark heart drug trial: ticagrelor PLATO study

Q: What is the clinical evidence from this study?

Population: Acute coronary syndrome. Intervention: Ticagrelor vs. Clopidogrel. Primary outcome: Data integrity, endpoint adjudication accuracy, and death reporting in the PLATO trial.

Q: What does this research mean for the field?

The pivotal PLATO trial supporting ticagrelor's superiority suffered from serious data reporting and quality flaws, including unpublished omissions of deaths and asymmetric event adjudication. Novelty: ClaimNovelty.CONTRADICTORY. Consensus alignment: ConsensusAlignment.CHALLENGES_CONSENSUS.

Peter Doshi

doi:10.1136/bmj.q2550

December 11, 2024BMJOpen Access

Doubts over landmark heart drug trial: ticagrelor PLATO study

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Why the study?

Does an investigation of primary PLATO trial records and unpublished FDA data support the reliability of ticagrelor's reported superiority over clopidogrel in patients with acute coronary syndrome?

Key Points

To re-evaluate the regulatory approval and evidentiary reliability of the landmark PLATO trial for the antiplatelet drug ticagrelor.
Documentary and investigative analysis of primary PLATO trial records, unpublished data obtained via freedom of information requests, and Food and Drug Administration (FDA) review memoranda.
Synthesis of post-licensure observational and randomized clinical studies evaluating ticagrelor against clopidogrel in acute coronary syndrome.
Although the original 18 624-patient PLATO trial reported a reduction in the primary composite endpoint from 11.7% with clopidogrel to 9.8% with ticagrelor (a 16% decrease in relative risk), a US subgroup analysis showed a 27% higher risk with ticagrelor.
FDA medical reviewer Thomas Marciniak recommended against approval in 2011 due to concerns over PLATO data quality and completeness, concluding ticagrelor appeared inferior to clopidogrel in US results.
Subsequent post-licensure studies and trials failed to replicate PLATO's findings, showing similar efficacy between drugs alongside increased bleeding and dyspnoea, including a Japanese trial with primary endpoint rates of 9.0% for ticagrelor versus 6.3% for clopidogrel.

Structured PICO

Does an investigation of primary PLATO trial records and unpublished FDA data support the reliability of ticagrelor's reported superiority over clopidogrel in patients with acute coronary syndrome?

P

Population

Patients with acute coronary syndrome included in the landmark PLATO trial (n=18,624 across 43 countries) whose primary trial records and FDA review documents were investigated.

I

Intervention

Ticagrelor

C

Comparator

Clopidogrel

O

Outcome

Reliability and accuracy of PLATO trial data reporting, including primary composite endpoint (death from vascular causes, myocardial infarction, or stroke at 12 months) adjudication and vital status reportingcomposite

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Implication

This investigative report uncovers significant data reporting omissions, endpoint adjudication asymmetries, and monitoring concerns in the landmark PLATO trial, supporting calls to reappraise guideline recommendations for ticagrelor over clopidogrel in acute coronary syndrome.

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

Discussion

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Cite This Study

Peter Doshi (2024) studied Acute coronary syndrome. Ticagrelor vs. Clopidogrel was evaluated on Data integrity, endpoint adjudication accuracy, and death reporting in the PLATO trial.

synapsesocial.com/papers/6a7849006c53f758bc1ec9a0 https://doi.org/10.1136/bmj.q2550

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Doubts over landmark heart drug trial: ticagrelor PLATO study

Key Points

Structured PICO

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Doubts over landmark heart drug trial: ticagrelor PLATO study

Key Points

Structured PICO

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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