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Randomized Controlled Trial
. 2014 Aug 14;35(31):2083-93.
doi: 10.1093/eurheartj/ehu160. Epub 2014 Apr 11.

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

Daniel Lindholm  1 , Christoph Varenhorst  1 , Christopher P Cannon  2 , Robert A Harrington  3 , Anders Himmelmann  4 , Juan Maya  5 , Steen Husted  6 , Philippe Gabriel Steg  7 , Jan H Cornel  8 , Robert F Storey  9 , Susanna R Stevens  10 , Lars Wallentin  1 , Stefan K James  11
Affiliations
Randomized Controlled Trial

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

Daniel Lindholm et al. Eur Heart J. .

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.

Keywords: Acute coronary syndrome; Platelet inhibition.

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Figures

Figure 1
Figure 1
Trial profile—patients classified by entry ECG and by treatment during the first 10 days after randomization.
Figure 2
Figure 2
Efficacy endpoints stratified by management strategy—Kaplan–Meier estimates of time to first occurrence of: (A) primary endpoint, (B) all-cause death, from 10 days post-randomization onward.
Figure 3
Figure 3
Bleeding stratified by revascularization—Kaplan–Meier estimate of (A) time to major bleeding according to the PLATO criteria from day 10 post-randomization, and (B) time to non-CABG major bleeding.
See this image and copyright information in PMC

Comment in

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