Efficacy and safety of ticagrelor for long-term secondary prevention of atherothrombotic events in relation to renal function: Insights from the PEGASUS-TIMI 54 trial

Giulia Magnani, Robert F. Storey, Gabriel Steg, Deepak L. Bhatt, Marc Cohen, Julia Kuder, Kyungah Im, Philip Aylward, Diego Ardissino, Daniel Isaza, Alexander Parkhomenko, Assen R. Goudev, Mikael Dellborg, Frederic Kontny, Ramon Corbalan, Felix Medina, Eva C. Jensen, Peter Held, Eugene Braunwald, Marc S. SabatineMarc P. Bonaca

Research output: Contribution to journalArticlepeer-review

69 Citations (Scopus)


We evaluated the relationship of renal function and ischaemic and bleeding risk as well as the efficacy and safety of ticagrelor in stable patients with prior myocardial infarction (MI). Methods and results Patients with a history of MI 1-3 years prior from PEGASUS-TIMI 54 were stratified based on estimated glomerular filtration rate (eGFR), with <60 mL/min/1.73 m2 pre-specified for analysis of the effect of ticagrelor on the primary efficacy composite of cardiovascular death, MI, or stroke (major adverse cardiovascular events, MACE) and the primary safety endpoint of TIMI major bleeding. Of 20 898 patients, those with eGFR <60 (N = 4849, 23.2%) had a greater risk of MACE at 3 years relative to those without, which remained significant after multivariable adjustment (hazard ratio, HRadj 1.54, 95% confidence interval, CI 1.27-1.85, P < 0.001). The relative risk reduction in MACE with ticagrelor was similar in those with eGFR <60 (ticagrelor pooled vs. placebo: HR 0.81; 95% CI 0.68-0.96) vs. ≥60 (HR 0.88; 95% CI 0.77-1.00, Pinteraction = 0.44). However, due to the greater absolute risk in the former group, the absolute risk reduction with ticagrelor was higher: 2.7 vs. 0.63%. Bleeding tended to occur more frequently in patients with renal dysfunction. The absolute increase in TIMI major bleeding with ticagrelor was similar in those with and without eGFR <60 (1.19 vs. 1.43%), whereas the excess of minor bleeding tended to be more pronounced (1.93 vs. 0.69%). Conclusion In patients with a history of MI, patients with renal dysfunction are at increased risk of MACE and consequently experience a particularly robust absolute risk reduction with long-term treatment with ticagrelor.

Original languageEnglish
Pages (from-to)400-408
Number of pages9
JournalEuropean heart journal
Issue number4
Publication statusPublished or Issued - 21 Jan 2016


  • Myocardial infarction
  • Renal dysfunction
  • Secondary prevention
  • Ticagrelor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this