title: Frailty is associated with worse outcomes in non-ST-segment elevation acute coronary syndromes: Insights from the TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medicallY manage Acute Coronary Syndromes (TRILOGY ACS) trial.
abstract: OBJECTIVE
  Little is known regarding consequences of frailty in patients with acute coronary syndrome (ACS). We assessed the associations of frailty and outcomes in ACS patients who were participating in a clinical trial.
  
  
  RESULTS
  The TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medicallY manage Acute Coronary Syndromes (TRILOGY ACS) trial randomized 9326 patients planned for medical management to prasugrel or clopidogrel. The primary endpoint was a composite of cardiovascular death, myocardial infarction (MI), or stroke over a period of 30 months. A frailty score based upon the Fried score was self-reported at baseline in patients aged ⩾65 years. Five frailty questions were recorded for 4996/5102 (97.9%) patients: 72.3% were classified as not-frail (0 items), 23.0% as pre-frail (1-2 items), and 4.7% as frail (⩾3 items). Increasing frailty score was associated with older age, diabetes, and higher Global Registry of Acute Coronary Events (GRACE) scores. Frailty was associated with a higher unadjusted incidence of the primary endpoint (pre-frail vs not-frail: 29.2% vs 23.1%; hazard ratio [HR]: 1.39; 95% confidence interval [CI]: 1.19-1.61; p<0.001; frail vs not-frail: 39.7% vs 23.1%; HR: 1.76; 95% CI: 1.36-2.28; p<0.001), and all-cause mortality (pre-frail vs not-frail: 21.7% vs 15.0%; HR: 1.45; 95% CI: 1.22-1.73; p<0.001; frail vs not-frail: 30.2% vs 15.0%; HR: 1.98; 95% CI: 1.47-2.68; p<0.001). After adjustment for baseline characteristics and GRACE covariates, frailty remained independently associated with the primary endpoint: pre-frail vs not-frail, HR: 1.33; 95% CI: 1.15-1.54; p<0.001; frail vs not-frail, HR: 1.52; 95% CI: 1.18-1.98; p=0.002. There was no association of frailty with bleeding.
  
  
  CONCLUSIONS
  Frailty is associated with the composite of cardiovascular death, MI, or stroke. Frailty assessment contributes to risk prediction and adds to the GRACE score.
authors.affiliation: Green Lane Cardiovascular Service, Auckland City Hospital and University of Auckland, Auckland, New Zealand HarveyW@adhb.govt.nz.
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.affiliation: Canadian VIGOUR Centre, University of Alberta, Canada.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Westerhout
authors.affiliation: Duke Clinical Research Institute, USA Division of Cardiology, Department of Medicine, Duke University School of Medicine, USA.
authors.forename: Karen P
authors.initials: KP
authors.lastname: Alexander
authors.affiliation: Duke Clinical Research Institute, USA Division of Cardiology, Department of Medicine, Duke University School of Medicine, USA.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Roe
authors.affiliation: Eli Lilly and Company, USA.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Winters
authors.affiliation: Duke Clinical Research Institute, USA.
authors.forename: Derek D
authors.initials: DD
authors.lastname: Cyr
authors.affiliation: Centre for Cardiovascular Science, University of Edinburgh, UK.
authors.forename: Keith Aa
authors.initials: KA
authors.lastname: Fox
authors.affiliation: Centre for Chronic Disease Control and Public Health Foundation of India, India.
authors.forename: Dorairaj
authors.initials: D
authors.lastname: Prabhakaran
authors.affiliation: Division of Cardiology, Department of Medicine, Langone Medical Center, New York University, USA.
authors.forename: Judith S
authors.initials: JS
authors.lastname: Hochman
authors.affiliation: Canadian VIGOUR Centre, University of Alberta, Canada Division of Cardiology, Department of Medicine, University of Alberta, Canada.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
authors.affiliation: Duke Clinical Research Institute, USA Division of Cardiology, Department of Medicine, Duke University School of Medicine, USA.
authors.forename: E Magnus
authors.initials: EM
authors.lastname: Ohman
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000401:mortality; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000077144:Clopidogrel; D004311:Double-Blind Method; D005260:Female; D016330:Frail Elderly; D006306:Health Surveys; D006801:Humans; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D000068799:Prasugrel Hydrochloride / Q000008:administration & dosage* / Q000627:therapeutic use; D011379:Prognosis; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine
keywords: Frailty; acute coronary syndrome; clinical trial; elderly; outcome assessment