Ticagrelor vs. clopidogrel in patients with non-ST-elevation acute coronary syndrome with or without revascularization: results from the PLATO trial.

Abstract

AIMS:

The optimal platelet inhibition strategy for ACS patients managed without revascularization is unknown. We aimed to evaluate efficacy and safety of ticagrelor vs. clopidogrel in the non-ST-elevation acute coronary syndrome (NSTE-ACS) subgroup of the PLATO trial, in the total cohort, and in the subgroups managed with and without revascularization within 10 days of randomization.

METHODS AND RESULTS:

We performed a retrospective analysis of the primary endpoint of cardiovascular death/myocardial infarction/stroke. Among 18 624 PLATO patients, 11 080 (59%) were categorized as NSTE-ACS at randomization. During the initial 10 days, 74% had angiography, 46% PCI, and 5% CABG. In NSTE-ACS patients, the primary endpoint was reduced with ticagrelor vs. clopidogrel [10.0 vs. 12.3%; hazard ratio (HR) 0.83; 95% confidence interval (CI) = 0.74-0.93], as was myocardial infarction (6.6 vs. 7.7%; HR 0.86; 95% CI = 0.74-0.99), cardiovascular death (3.7 vs. 4.9%; HR 0.77; 95% CI = 0.64-0.93), and all-cause death (4.3 vs. 5.8%; HR 0.76; 95% CI = 0.64-0.90). Major bleeding rate was similar between treatment groups (13.4 vs. 12.6%; HR 1.07; 95% CI = 0.95-1.19), but ticagrelor was associated with an increase in non-CABG major bleeding (4.8 vs. 3.8%; HR 1.28; 95% CI = 1.05-1.56). Within the first 10 days, 5366 (48.4%) patients were managed without revascularization. Regardless of revascularization or not, ticagrelor consistently reduced the primary outcome (HR 0.86 vs. 0.85, interaction P = 0.93), and all-cause death (HR 0.75 vs. 0.73, interaction P = 0.89) with no significant increase in overall major bleeding.

CONCLUSION:

In patients with NSTE-ACS, benefit of ticagrelor over clopidogrel in reducing ischaemic events and total mortality was consistent with the overall PLATO trial, independent of actually performed revascularization during the initial 10 days.

• Authors: Daniel Lindholm, Christoph Varenhorst, Christopher P Cannon, Robert A Harrington, Anders Himmelmann, Juan Maya, Steen Husted, Philippe Gabriel Steg, Jan H Cornel, Robert F Storey, Susanna R Stevens, Lars Wallentin, Stefan K James
• Journal: European heart journal (Eur Heart J) Vol. 35 Issue 31 Pg. 2083-93 (Aug 14 2014) ISSN: 1522-9645 [Electronic] England
• PMID: 24727884 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.

Chemical References

• Platelet Aggregation Inhibitors
• Clopidogrel
• Ticagrelor
• Adenosine
• Ticlopidine

Topics

• Acute Coronary Syndrome (drug therapy, mortality)
• Adenosine (analogs & derivatives, therapeutic use)
• Aged
• Clopidogrel
• Female
• Hemorrhage (chemically induced)
• Humans
• Kaplan-Meier Estimate
• Male
• Myocardial Infarction (etiology, mortality)
• Myocardial Revascularization (mortality, statistics & numerical data)
• Platelet Aggregation Inhibitors (therapeutic use)
• Retrospective Studies
• Ticagrelor
• Ticlopidine (analogs & derivatives, therapeutic use)
• Treatment Outcome