title: 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.
abstract: OBJECTIVE
  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).
  
  
  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 m(2) 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%).
  
  
  CONCLUSIONS
  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.
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA, USA.
authors.forename: Giulia
authors.initials: G
authors.lastname: Magnani
authors.affiliation: Department of Cardiovascular Science, University of Sheffield, Sheffield, UK.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Storey
authors.affiliation: Cardiology Department, DHU-FIRE, Hôpital Bichat, Paris, France Université Paris-Diderot, Paris, France INSERM U1148, Paris, France.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Steg
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA, USA.
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.affiliation: Cardiovascular Division, Department of Medicine, Rutgers-New Jersey Medical School, New York, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Cohen
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Kuder
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA, USA.
authors.forename: Kyungah
authors.initials: K
authors.lastname: Im
authors.affiliation: Division of Medicine, Cardiac & Critical Care Services, Flinders University and Medical Centre, Adelaide, Australia.
authors.forename: Philip
authors.initials: P
authors.lastname: Aylward
authors.affiliation: Cardiovascular Division, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Ardissino
authors.affiliation: Fundacion CardioInfantil, Bogota, Colombia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Isaza
authors.affiliation: Ukranian Strazhesko Institute of Cardiology, Kiev, Ukraine.
authors.forename: Alexander
authors.initials: A
authors.lastname: Parkhomenko
authors.affiliation: Department of Cardiology, Queen Giovanna University Hospital, Sofia, Bulgaria.
authors.forename: Assen R
authors.initials: AR
authors.lastname: Goudev
authors.affiliation: Department of Molecular and Clinical Medicine/Cardiology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Dellborg
authors.affiliation: Department of Cardiology, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Frederic
authors.initials: F
authors.lastname: Kontny
authors.affiliation: Cardiovascular Division, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Ramon
authors.initials: R
authors.lastname: Corbalan
authors.affiliation: Hospital Nacional Cayetano Heredia, San Martin de Porres, Lima, Peru.
authors.forename: Felix
authors.initials: F
authors.lastname: Medina
authors.affiliation: AstraZenecaAZ R&D, Molndal, Sweden.
authors.forename: Eva C
authors.initials: EC
authors.lastname: Jensen
authors.affiliation: AstraZenecaAZ R&D, Molndal, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Held
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA, USA.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Sabatine
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA, USA mbonaca@partners.org.
authors.forename: Marc P
authors.initials: MP
authors.lastname: Bonaca
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000368:Aged; D003324:Coronary Artery Disease / Q000401:mortality / Q000517:prevention & control*; D003328:Coronary Thrombosis / Q000401:mortality / Q000517:prevention & control*; D004334:Drug Administration Schedule; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000401:mortality; D012307:Risk Factors; D000077486:Ticagrelor; D016896:Treatment Outcome
chemical_list: D058921:Purinergic P2Y Receptor Antagonists; D000077486:Ticagrelor; D000241:Adenosine
keywords: Myocardial infarction; Renal dysfunction; Secondary prevention; Ticagrelor