Mortality in the TRACER and ATLAS ACS 2 trials: two more reasons to audit vital records in PLATO

Abstract

Context: Extreme rates of vascular and all-cause mortality, especially in the clopidogrel arm of the PLATO (PLATelet Inhibition and Clinical Outcomes) trial, raise concerns of data accuracy and call for independent verification of vital records in the national death registries. Two recently completed acute coronary syndrome (ACS) trials, TRACER and ATLAS ACS 2 (Thrombin Receptor Antagonist for Clinical Event Reduction in ACS and Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with ACS-Thrombolysis in Myocardial Infarction), provide a valuable opportunity to match mortality numbers among 3 similar studies.

Objective: To compare the rates of vascular and all-cause mortality in the PLATO, TRACER and ATLAS ACS 2 trials.

Results: Despite a shorter mean follow-up (277 days) for the PLATO trial than for the TRACER (502 days) or ATLAS ACS 2 (393 days) trials, both vascular (5.1%) and all-cause (5.9%) mortality in PLATO were higher than in the TRACER (3.2 and 4.9%) or ATLAS ACS 2 (4.1 and 4.5%) control arms, respectively. Adjusting for follow-up duration, rates of vascular (0.0184/day), or all-cause (0.0213/day) mortality in PLATO differ importantly from daily death rates in TRACER (0.0063 and 0.0097) and ATLAS ACS 2 (0.0104 and 0.0115), suggesting that the risk of death in the control PLATO arm was approximately double that of the other trials. The mismatch is particularly striking considering that ATLAS ACS 2 enrolled more STEMI (ST-segment elevation in myocardial infarction) patients (50.9%) than PLATO (38.0%).

Conclusions: Both overall and follow-up duration-adjusted mortality rates in PLATO far exceeded the risk of death observed in the two recent ACS trials. The background STEMI rates are not likely to be responsible for the PLATO mortality paradox. These data provide an additional reason to request an independent audit of the deceased PLATO clopidogrel cohort.