Key result
Ticagrelor shows no benefit over clopidogrel for major CV events in ACS patients undergoing CABG.
Why the study?
The efficacy and safety of ticagrelor compared with clopidogrel in patients with acute coronary syndrome undergoing CABG as a post-randomization strategy were evaluated.
Does ticagrelor reduce the composite of CV death, MI, or stroke compared to clopidogrel in patients with acute coronary syndromes undergoing CABG?
RCT (n=1,261)
Double-blind
Randomized
Does ticagrelor reduce the composite of CV death, MI, or stroke compared to clopidogrel in patients with acute coronary syndromes undergoing CABG?
Answers are grounded in this paper and cite their sources.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Ticagrelor seems to be a very promising alternative to clopidogrel for patients with acute coronary syndrome who might be candidates for CABG surgery, because of the significant reduction in mortality and the similar bleeding rate. Because there is such an obvious risk of severe bleeding and fatal complications during surgery, patients with a potential need for CABG comprise an especially important group, for which platelet inhibitors with a better safety-efficacy profile are needed.”
“We did see about a 50% reduction in mortality in these patients but without any increase in the bleeding complications. We have looked at several different definitions of bleeding and do not see any sign of increases in bleeding, despite this reduction in mortality.”
“This is a great and important study that raises lots of issues. There wasn't any difference in major bleeding, and yet the results were better in terms of a reduction in mortality. So the question then is: Are there other effects? A more potent agent should give you more bleeding, but this didn't. Are there pleiotropic effects of this particular medication?”
In patients with acute coronary syndromes undergoing CABG within 7 days of last study drug intake, ticagrelor significantly reduced total and cardiovascular mortality compared to clopidogrel without increasing CABG-related bleeding.
OBJECTIVES: The purpose of this study is to evaluate the efficacy and safety of ticagrelor and clopidogrel in patients with acute coronary syndrome undergoing coronary artery bypass graft surgery (CABG), as a post-randomization strategy. BACKGROUND: Ticagrelor is a novel, reversibly binding, oral, direct-acting P2Y(12)-receptor antagonist. In the PLATO (Platelet Inhibition and Patient Outcomes) trial, which randomized 18,624 patients with acute coronary syndromes, ticagrelor compared with clopidogrel significantly reduced the risk of the primary composite end point of cardiovascular (CV) death, myocardial infarction, or stroke (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.77 to 0.92; p < 0.001). This report investigated the outcomes of patients treated with CABG during the trial. METHODS: In total, 1,899 patients underwent CABG post-randomization. The protocol recommended ticagrelor/placebo to be withheld for 24 to 72 h and clopidogrel/placebo for 5 days preoperatively. In all, 1,261 patients underwent CABG and were receiving study drug treatment <7 days before surgery. The statistical analysis was based on events occurring from the CABG procedure until the end of the study, excluding 3 patients with CABG after study end. RESULTS: In the 1,261 patient cohort, the relative reduction of primary composite end point at 12 months (10.6% [66 of 629] with ticagrelor versus 13.1% [79 of 629] with clopidogrel; HR: 0.84; 95% CI: 0.60 to 1.16; p = 0.29) was consistent with the results of the whole trial. Total mortality was reduced from 9.7% (58 of 629) to 4.7% (29 of 629; HR: 0.49; 95% CI: 0.32 to 0.77; p < 0.01), CV death from 7.9% (47 of 629) to 4.1% (25 of 629; HR: 0.52; 95% CI: 0.32 to 0.85; p < 0.01), and non-CV death numerically from 2.0% to 0.7% (p = 0.07). There was no significant difference in CABG-related major bleeding between the randomized treatments. CONCLUSIONS: In the subgroup of patients undergoing CABG within 7 days after the last study drug intake, ticagrelor compared with clopidogrel was associated with a substantial reduction in total and CV mortality without excess risk of CABG-related bleeding.
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Held et al. (2010) conducted an RCT in Acute coronary syndromes undergoing coronary artery bypass graft surgery (CABG) (n=1,261). Ticagrelor vs. Clopidogrel was evaluated on Primary composite end point of cardiovascular (CV) death, myocardial infarction, or stroke (HR 0.84, 95% CI 0.60 to 1.16, p=0.29). Ticagrelor did not significantly reduce the primary composite endpoint of CV death, MI, or stroke compared to clopidogrel in patients with ACS undergoing CABG (HR 0.84; 95% CI 0.60-1.16; P=0.29).
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