Mortality after clopidogrel in the non-invasive PLATO cohort and TRILOGY ACS trial: another mismatched death paradox

Abstract

Background: Excess mortality especially in the clopidogrel arm of the PLATO trial raise concerns of data integrity, and call for independent verification of vital records in the national death registries. Recently published data focused on outcomes in patients after non-invasive strategies yielded from the PLATO (PLATO-NIS) and TRILOGY ACS trials allowing comparison of all cause mortality (ACM) between trials.

Methods: To compare the prorated over follow-up duration rates of ACM in the clopidogrel arms of PLATO-NIS cohort and TRILOGY ACS trial.

Results: The background clinical characteristics indicate similar if not higher mortality should be expected in TRILOGY ACS. PLATO trial was almost half the duration with a mean follow-up of 277 days compared to TRILOGY ACS (513 days). Matching prorated over follow-up duration of ACM rates in the clopidogrel arm revealed 0.027/day or 9.86% yearly mortality in PLATO-NIS cohort (195 fatalities among 2615 patients enrolled). The ACM rates in TRILOGY ACS (409/4663) were only 0.017/day or 6.2% annually after clopidogrel, suggesting that the risk to die in the control PLATO-NIS group was 63% higher and barely missed significance (p=0.051) compared to TRILOGY ACS.

Conclusions: Prorated over length of follow-up PLATO-NIS mortality rates after clopidogrel far exceeded those observed in a similar medically managed patients in a TRILOGY ACS trial. The background clinical differences between trials are not responsible for the elevated PLATO-NIS mortality numbers. These data further challenge the death paradox reported in the overall PLATO trial and call for the urgent independent verification of vital records.

Keywords: Acute coronary syndromes; Clinical trials; Mortality; Non invasive strategy.