Renewed Controversy regarding benefits of Ticagrelor

 A BMJ investigation is revisiting the PLATO trial, which launched ticagrelor (Brilinta; AstraZeneca) 15 years ago.

• The investigation raises questions about the drug's efficacy compared to generic alternatives in modern practice.

• The PLATO trial, published in 2009, claimed ticagrelor reduced vascular death, MI, or stroke compared to clopidogrel, despite increasing major bleeding unrelated to CABG.

• These results supported FDA approval in 2011, despite concerns over subgroup analysis indicating worse outcomes for US patients.

• Criticisms of the PLATO trial’s conduct have persisted, including a Department of Justice investigation from 2013-2014, which ended due to insufficient evidence.

• The new BMJ article highlights alleged issues with how certain death categories in the trial were adjudicated to favor ticagrelor.

• It suggests discrepancies in primary trial records and site-level death data, some of which were not included in the original trial results.

• Defenders of the PLATO trial argue that no significant new information has been added to the debate.

• Observational and randomized studies since the PLATO trial have failed to replicate its results, particularly in the context of modern treatment advancements.

• The ISAR-REACT 5 trial found prasugrel outperformed ticagrelor for patients undergoing revascularization.

• Both prasugrel and ticagrelor pose higher bleeding risks compared to clopidogrel.

• Cost is a significant barrier; ticagrelor accounted for less than 10% of P2Y12 prescriptions but two-thirds of the cost in 2022, with the US government spending over $750 million.

• Experts suggest ticagrelor’s benefit may be limited to specific populations, such as those with high thrombotic risk and low bleeding risk.

• Calls for a guideline reassessment remain divided, with some advocating for a thorough review of PLATO trial data.

• The lack of confirmatory studies in modern practice further fuels the debate over ticagrelor's relevance today.

---

Key Takeaways:

• PLATO trial remains under scrutiny for potential biases favoring ticagrelor.

• Modern clinical advancements and studies challenge ticagrelor's superiority over generics like clopidogrel.

• Bleeding risk and cost are significant barriers to widespread use of ticagrelor.

• The guidelines supporting ticagrelor may warrant reevaluation based on contemporary evidence.

• Further investigations, including possible involvement of the Department of Justice, are being called for by critics.

Learn More from the Article