Factors Contributing to the Lower Mortality With Ticagrelor Compared With Clopidogrel in Patients Undergoing Coronary Artery Bypass Surgery

Study Questions:

In the PLATO (Platelet Inhibition and Patient Outcomes) trial, patients who were assigned to ticagrelor and underwent coronary artery bypass graft surgery (CABG) had significantly lower total and cardiovascular mortality compared with those assigned to clopidogrel. What are the differences in specific causes of post–CABG deaths in the PLATO trial?

Methods:

In the PLATO trial, 1,261 patients underwent CABG within 7 days after stopping the study drug. Reviewers blinded to treatment assignment classified causes of death into subcategories of vascular and nonvascular, and specifically identified bleeding or infection events that either caused or subsequently contributed to death.

Results:

Among factors directly causing or contributing to death, bleeding (27 vs. 9, p < 0.01) and infections (16 vs. 6, p < 0.05) were more common in the clopidogrel group compared with the ticagrelor group. There were numerically more vascular deaths in the clopidogrel arm versus the ticagrelor group related to myocardial infarction (14 vs. 10), heart failure (9 vs. 6), arrhythmia or sudden death (9 vs. 3), and bleeding, including hemorrhagic stroke (7 vs. 2). Clopidogrel was also associated with an excess of nonvascular deaths related to infection (8 vs. 2).

Conclusions:

The mortality reduction with ticagrelor versus clopidogrel following CABG in the PLATO trial was associated with fewer deaths from cardiovascular, bleeding, and infection complications.

Perspective:

This interesting study demonstrates that patients who had been treated with ticagrelor and then underwent CABG had lower mortality from both cardiovascular causes as well as infection and bleeding. Because ticagrelor was held for 1 week in this study, the mechanism of this finding remains unclear (since the drug effect would be minimal to absent at that point). Nevertheless, the findings of this study mirror the survival benefit that was demonstrated in the overall PLATO trial, and suggest a greater role for ticagrelor in patients with acute coronary syndromes.

Clinical Topics: Acute Coronary Syndromes, Arrhythmias and Clinical EP, Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, SCD/Ventricular Arrhythmias, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Acute Heart Failure, Interventions and ACS, Interventions and Imaging, Computed Tomography, Nuclear Imaging

Keywords: Myocardial Infarction, Stroke, Acute Coronary Syndrome, Platelet Aggregation Inhibitors, Tomography, X-Ray Computed, Tin Fluorides, Ticlopidine, Blood Platelets, Purinergic P2Y Receptor Antagonists, Heart Failure, Cardiovascular Diseases, Organoplatinum Compounds, Coronary Artery Bypass, Death, Sudden, Cardiac, Hemorrhage


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