Efficacy and safety with ticagrelor in patients with prior myocardial infarction in the approved European label: insights from PEGASUS-TIMI 54

Mikael Dellborg, Marc P Bonaca, Robert F Storey, P Gabriel Steg, Kyung A Im, Marc Cohen, Deepak L Bhatt, Ton Oude Ophuis, Andrezej Budaj, Christian Hamm, Jindrich Spinar, Robert G Kiss, José Lopez-Sendon, Gabriel Kamensky, Frans Van de Werf, Diego Ardissino, Frederic Kontny, Gilles Montalescot, Per Johanson, Olof Bengtsson, Anders Himmelmann, Eugene Braunwald, Marc S Sabatine, Mikael Dellborg, Marc P Bonaca, Robert F Storey, P Gabriel Steg, Kyung A Im, Marc Cohen, Deepak L Bhatt, Ton Oude Ophuis, Andrezej Budaj, Christian Hamm, Jindrich Spinar, Robert G Kiss, José Lopez-Sendon, Gabriel Kamensky, Frans Van de Werf, Diego Ardissino, Frederic Kontny, Gilles Montalescot, Per Johanson, Olof Bengtsson, Anders Himmelmann, Eugene Braunwald, Marc S Sabatine

Abstract

Aims: In PEGASUS-TIMI 54, ticagrelor significantly reduced the risk of the composite of major adverse cardiovascular (CV) events by 15-16% in stable patients with a prior myocardial infarction (MI) 1-3 years earlier. We report the efficacy and safety in the subpopulation recommended for treatment in the European (EU) label, i.e. treatment with 60 mg b.i.d. initiated up to 2 years from the MI, or within 1 year after stopping previous adenosine diphosphate receptor inhibitor treatment.

Methods and results: Of the 21 162 patients enrolled in PEGASUS-TIMI 54, 10 779 patients were included in the primary analysis for this study, randomized to ticagrelor 60 mg (n = 5388) or matching placebo (n = 5391). The cumulative proportions of patients with events at 36 months were calculated by the Kaplan-Meier (KM) method. The composite of CV death, MI, or stroke occurred less frequently in the ticagrelor group (7.9% KM rate vs. 9.6%), hazard ratio (HR) 0.80 [95% confidence interval (CI) 0.70-0.91; P = 0.001]. Ticagrelor also reduced the risk of all-cause mortality, HR 0.80 (0.67-0.96; P = 0.018). Thrombolysis in myocardial infarction major bleeding was more frequent in the ticagrelor group 2.5% vs. 1.1%; HR 2.36 (1.65-3.39; P < 0.001). The corresponding HR for fatal or intracranial bleeding was 1.17 (0.68-2.01; P = 0.58).

Conclusion: In PEGASUS-TIMI 54, treatment with ticagrelor 60 mg as recommended in the EU label, was associated with a relative risk reduction of 20% in CV death, MI, or stroke. Thrombolysis in myocardial infarction major bleeding was increased, but fatal or intracranial bleeding was similar to placebo. There appears to be a favourable benefit-risk ratio for long-term ticagrelor 60 mg in this population.

Clinical trial registration: http://www.clinicaltrials.gov NCT01225562.

Keywords: Coronary artery disease; Dual antiplatelet treatment; Post-myocardial infarction.

© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.

Figures

Figure 1
Figure 1
Primary endpoint for ticagrelor 60 mg vs. placebo, European label and non-European label patients. T60 EU: ticagrelor 60 mg according to European label. Placebo EU: placebo treatment according to European label. T60 N-EU: ticagrelor 60 mg to non-European label patients. Placebo N-EU: placebo treatment to non-European label patients.
Figure 2
Figure 2
All-cause death for ticagrelor 60 mg vs. placebo, European label and non-European label patients. T60 EU: ticagrelor 60 mg according to European label. Placebo EU: placebo treatment according to European label. T60 N-EU: ticagrelor 60 mg to non-European label patients. Placebo N-EU: placebo treatment to non-European label patients.
Figure 3
Figure 3
Clinical events prevented and caused per 1000 patients initiated on ticagrelor 60 mg b.i.d. and followed for 3 years.

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