Infections Deaths in the PLATO Trial

Area of Science:

• Cardiology
• Clinical Trials
• Pharmacology

Background:

• Dual antiplatelet therapy (DAPT) offers cardiovascular benefits but carries risks like bleeding, cancer, and infections.
• Prasugrel's risks were identified in the TRITON trial; ticagrelor in PLATO showed more infections but fewer sepsis-related deaths (SRD) than clopidogrel.
• Verified infection fatalities in PLATO were not publicly available, prompting an analysis of FDA data.

Purpose of the Study:

• To analyze Food and Drug Administration (FDA)-issued death data from the PLATO trial.
• To verify infection-related fatalities, specifically pneumonia and sepsis-related deaths (SRD), reported in the PLATO trial.
• To assess the accuracy of SRD reporting and compare infection death patterns between ticagrelor and clopidogrel.

Main Methods:

• Obtained the complete FDA primary causes death list for the PLATO trial.
• Matched FDA records with available local site data for pneumonia and SRD.
• Analyzed patterns of infections and deaths, focusing on SRD within the nonvascular death dataset.

Main Results:

• FDA records indicated fewer pneumonia deaths with clopidogrel (8) than ticagrelor (10), but over three times more SRD (23 vs. 7).
• Verification confirmed pneumonia deaths but found two clopidogrel SRD were incorrect.
• Potential misreporting of SRD was observed, including duplicate entries and apparent compensation between drug groups.

Conclusions:

• FDA data suggests ticagrelor offers no advantage in preventing infection-related deaths, with more pneumonia deaths and potential SRD misreporting in PLATO.
• The findings indicate a need for a precise review of sepsis deaths in the PLATO trial.
• Accurate reporting of infection fatalities is crucial for evaluating the safety profiles of antiplatelet therapies.