Factors contributing to the lower mortality with ticagrelor compared with clopidogrel in patients undergoing coronary
Christoph Varenhorst1, Ulrica Alström, Benjamin M Scirica
1Uppsala Clinical Research Center and Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden. christoph.varenhorst@ucr.uu.se
Insights
Ticagrelor reduced deaths after coronary artery bypass graft (CABG) surgery compared to clopidogrel in the PLATO trial. This benefit was linked to fewer deaths from bleeding and infection complications.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- The Platelet Inhibition and Patient Outcomes (PLATO) trial demonstrated lower mortality with ticagrelor versus clopidogrel in patients undergoing coronary artery bypass graft (CABG) surgery.
- Specific causes of death post-CABG require detailed investigation to understand treatment effects.
Purpose of the Study:
- To investigate the specific causes of death following coronary artery bypass graft (CABG) surgery in patients from the PLATO trial.
- To compare the incidence of vascular and non-vascular death causes between ticagrelor and clopidogrel treatment groups post-CABG.
Main Methods:
- Analysis of 1,261 patients who underwent CABG within 7 days of study drug cessation in the PLATO trial.
- Blinded reviewers classified causes of death into vascular and non-vascular subcategories.
- Specific identification of bleeding and infection events contributing to mortality.
Main Results:
- Patients receiving clopidogrel experienced numerically higher vascular deaths (myocardial infarction, heart failure, arrhythmia, bleeding) and non-vascular deaths (infection) compared to ticagrelor.
- Bleeding events, including hemorrhagic stroke, were more frequent in the clopidogrel group.
- Infections were significantly more common as a cause of death in the clopidogrel group (16 vs. 6, p < 0.05).
Conclusions:
- Mortality reduction with ticagrelor over clopidogrel post-CABG in the PLATO trial is associated with decreased deaths from cardiovascular events.
- Fewer deaths attributed to bleeding complications were observed with ticagrelor.
- Ticagrelor use was linked to a significant reduction in infection-related deaths following CABG surgery.
Objectives:
This study investigated the differences in specific causes of post-coronary artery bypass graft surgery (CABG) deaths in the PLATO (Platelet Inhibition and Patient Outcomes) trial.
Background:
In the PLATO trial, patients assigned to ticagrelor compared with clopidogrel and who underwent CABG had significantly lower total and cardiovascular mortality.
Methods:
In the 1,261 patients with CABG performed within 7 days after stopping 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:
Numerically more vascular deaths occurred in the clopidogrel 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). Among factors directly causing or contributing to death, bleeding and infections were more common in the clopidogrel group compared with the ticagrelor group (infections: 16 vs. 6, p < 0.05, and bleeding: 27 vs. 9, p < 0.01, for clopidogrel and ticagrelor, respectively).
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. (Platelet Inhibition and Patient Outcomes [PLATO]; NCT00391872).
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