title: Early invasive versus non-invasive treatment in patients with non-ST-elevation acute coronary syndrome (FRISC-II): 15 year follow-up of a prospective, randomised, multicentre study.
abstract: The FRISC-II trial was the first randomised trial to show a reduction in death or myocardial infarction with an early invasive versus a non-invasive treatment strategy in patients with non-ST-elevation acute coronary syndrome. Here we provide a remaining lifetime perspective on the effects on all cardiovascular events during 15 years' follow-up.
  
  
  
  The FRISC-II prospective, randomised, multicentre trial was done at 58 Scandinavian centres in Sweden, Denmark, and Norway. Between June 17, 1996, and Aug 28, 1998, we randomly assigned (1:1) 2457 patients with non-ST-elevation acute coronary syndrome to an early invasive treatment strategy, aiming for revascularisation within 7 days, or a non-invasive strategy, with invasive procedures at recurrent symptoms or severe exercise-induced ischaemia. Plasma for biomarker analyses was obtained at randomisation. For long-term outcomes, we linked data with national health-care registers. The primary endpoint was a composite of death or myocardial infarction. Outcomes were compared as the average postponement of the next event, including recurrent events, calculated as the area between mean cumulative count-of-events curves. Analyses were done by intention to treat.
  
  
  
  At a minimum of 15 years' follow-up on Dec 31, 2014, data for survival status and death were available for 2421 (99%) of the initially recruited 2457 patients, and for other events after 2 years for 2182 (89%) patients. During follow-up, the invasive strategy postponed death or next myocardial infarction by a mean of 549 days (95% CI 204-888; p=0·0020) compared with the non-invasive strategy. This effect was larger in non-smokers (mean gain 809 days, 95% CI 402-1175; pinteraction=0·0182), patients with elevated troponin T (778 days, 357-1165; pinteraction=0·0241), and patients with high concentrations of growth differentiation factor-15 (1356 days, 507-1650; pinteraction=0·0210). The difference was mainly driven by postponement of new myocardial infarction, whereas the early difference in mortality alone was not sustained over time. The invasive strategy led to a mean of 1128 days (95% CI 830-1366) postponement of death or next readmission to hospital for ischaemic heart disease, which was consistent in all subgroups (p<0·0001).
  
  
  
  During 15 years of follow-up, an early invasive treatment strategy postponed the occurrence of death or next myocardial infarction by an average of 18 months, and the next readmission to hospital for ischaemic heart disease by 37 months, compared with a non-invasive strategy in patients with non-ST-elevation acute coronary syndrome. This remaining lifetime perspective supports that an early invasive treatment strategy should be the preferred option in most patients with non-ST-elevation acute coronary syndrome.
  
  
  
  Swedish Heart-Lung Foundation, Swedish Foundation for Strategic Research, and Uppsala Clinical Research Center.
authors: Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden. Electronic address: lars.wallentin@ucr.uu.se.
authors: Lars
authors: L
authors: Wallentin
authors: Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors: Lars
authors: L
authors: Lindhagen
authors: Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors: Elisabet
authors: E
authors: Ärnström
authors: Medical Department, Hospital Unit West, Herning/Holstebro, Denmark.
authors: Steen
authors: S
authors: Husted
authors: Department of Cardiology and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; Division of Health Care Analysis, Department of Medical and Health Sciences, Center for Medical Technology Assessment, Linköping University, Linköping, Sweden.
authors: Magnus
authors: M
authors: Janzon
authors: Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
authors: Søren Paaske
authors: SP
authors: Johnsen
authors: Stavanger University Hospital, Department of Cardiology, Stavanger, Norway; Drammen Heart Center, Drammen, Norway.
authors: Frederic
authors: F
authors: Kontny
authors: Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors: Tibor
authors: T
authors: Kempf
authors: Department of Cardiology and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; Division of Health Care Analysis, Department of Medical and Health Sciences, Center for Medical Technology Assessment, Linköping University, Linköping, Sweden.
authors: Lars-Åke
authors: LÅ
authors: Levin
authors: Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors: Bertil
authors: B
authors: Lindahl
authors: Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.
authors: Mats
authors: M
authors: Stridsberg
authors: Department of Surgical Sciences, Thoracic Surgery, Uppsala University, Uppsala, Sweden.
authors: Elisabeth
authors: E
authors: Ståhle
authors: Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.
authors: Per
authors: P
authors: Venge
authors: Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors: Kai C
authors: KC
authors: Wollert
authors: Department of Cardiology and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors: Eva
authors: E
authors: Swahn
authors: Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors: Bo
authors: B
authors: Lagerqvist
mesh_terms: D054058:Acute Coronary Syndrome / Q000401:mortality* / Q000503:physiopathology / Q000601:surgery / Q000628:therapy*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D048909:Diabetes Complications / Q000401:mortality / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D006329:Heart Conduction System / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000150:complications; D008297:Male; D008875:Middle Aged; D019060:Minimally Invasive Surgical Procedures; D009203:Myocardial Infarction / Q000401:mortality / Q000628:therapy; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010359:Patient Readmission / Q000706:statistics & numerical data*; D010446:Peptide Fragments / Q000097:blood; D011446:Prospective Studies; D012537:Scandinavian and Nordic Countries / Q000453:epidemiology; D055502:Secondary Prevention; D013997:Time Factors; D016896:Treatment Outcome; D020107:Troponin T / Q000097:blood
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain