title: Randomized trial of switching from prescribed non-selective non-steroidal anti-inflammatory drugs to prescribed celecoxib: the Standard care vs. Celecoxib Outcome Trial (SCOT).
abstract: BACKGROUND
  Selective cyclooxygenase-2 inhibitors and conventional non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) have been associated with adverse cardiovascular (CV) effects. We compared the CV safety of switching to celecoxib vs. continuing nsNSAID therapy in a European setting.
  
  
  METHODS
  Patients aged 60 years and over with osteoarthritis or rheumatoid arthritis, free from established CV disease and taking chronic prescribed nsNSAIDs, were randomized to switch to celecoxib or to continue their previous nsNSAID. The primary endpoint was hospitalization for non-fatal myocardial infarction or other biomarker positive acute coronary syndrome, non-fatal stroke or CV death analysed using a Cox model with a pre-specified non-inferiority limit of 1.4 for the hazard ratio (HR).
  
  
  RESULTS
  In total, 7297 participants were randomized. During a median 3-year follow-up, fewer subjects than expected developed an on-treatment (OT) primary CV event and the rate was similar for celecoxib, 0.95 per 100 patient-years, and nsNSAIDs, 0.86 per 100 patient-years (HR = 1.12, 95% confidence interval, 0.81-1.55; P = 0.50). Comparable intention-to-treat (ITT) rates were 1.14 per 100 patient-years with celecoxib and 1.10 per 100 patient-years with nsNSAIDs (HR = 1.04; 95% confidence interval, 0.81-1.33; P = 0.75). Pre-specified non-inferiority was achieved in the ITT analysis. The upper bound of the 95% confidence limit for the absolute increase in OT risk associated with celecoxib treatment was two primary events per 1000 patient-years exposure. There were only 15 adjudicated secondary upper gastrointestinal complication endpoints (0.078/100 patient-years on celecoxib vs. 0.053 on nsNSAIDs OT, 0.078 vs. 0.053 ITT). More gastrointestinal serious adverse reactions and haematological adverse reactions were reported on nsNSAIDs than celecoxib, but more patients withdrew from celecoxib than nsNSAIDs (50.9% patients vs. 30.2%; P < 0.0001).
  
  
  CONCLUSIONS
  In subjects 60 years and over, free from CV disease and taking prescribed chronic nsNSAIDs, CV events were infrequent and similar on celecoxib and nsNSAIDs. There was no advantage of a strategy of switching prescribed nsNSAIDs to prescribed celecoxib. This study excluded an increased risk of the primary endpoint of more than two events per 1000 patient-years associated with switching to prescribed celecoxib.
  
  
  BACKGROUND
  https://clinicaltrials.gov/show/NCT00447759; Unique identifier: NCT00447759.
authors.affiliation: Medicines Monitoring Unit (MEMO), Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital & Medical School Dundee, Dundee DD1 9SY, UK.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: MacDonald
authors.affiliation: Faculty of Medicine & Health Sciences, University of Nottingham, Queen's Medical Centre Nottingham, Nottingham NG7 2UH, UK.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Hawkey
authors.affiliation: Robertson Centre for Biostatistics, University of Glasgow, Glasgow G12 8QQ, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Ford
authors.affiliation: British Heart Foundation Cardiovascular Research Centre, University of Glasgow,126 University Place, GlasgowG12 8TA, UK.
authors.forename: John J V
authors.initials: JJV
authors.lastname: McMurray
authors.affiliation: Division of Gastroenterology, University of Michigan Medical School, 1500 E Medical Center Drive, Ann Arbor, MI 48109, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Scheiman
authors.affiliation: Department of Public Health, Clinical Pharmacology, University of Southern Denmark, J. B. Winsløws Vej 19, 2.5000 Odense, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Hallas
authors.affiliation: Medicines Monitoring Unit (MEMO), Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital & Medical School Dundee, Dundee DD1 9SY, UK.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Findlay
authors.affiliation: Julius Center for Health Sciences and Primary Care and Julius Clinical Academic Research Organization, Utrecht, The Netherlands.
authors.forename: Diederick E
authors.initials: DE
authors.lastname: Grobbee
authors.affiliation: Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Primary Care Building, Radcliffe Observatory Quarter, Woodstock Road, Oxford OX2 6GG, UK.
authors.forename: F D Richard
authors.initials: FDR
authors.lastname: Hobbs
authors.affiliation: Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital Edinburgh, Edinburgh EH4 2XU, UK.
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Ralston
authors.affiliation: School of Medicine & Dentistry, University of Aberdeen, Aberdeen AB25 2ZD, UK.
authors.forename: David M
authors.initials: DM
authors.lastname: Reid
authors.affiliation: British Heart Foundation Cardiovascular Research Centre, University of Glasgow,126 University Place, GlasgowG12 8TA, UK.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Walters
authors.affiliation: School of Medicine & Dentistry, University of Aberdeen, Aberdeen AB25 2ZD, UK.
authors.forename: John
authors.initials: J
authors.lastname: Webster
authors.affiliation: Department of Cardiology, University Heart Center, Rämistrasse 100, 8091Zürich, Switzerland.
authors.forename: Frank
authors.initials: F
authors.lastname: Ruschitzka
authors.affiliation: Centre of Academic Primary Care, School of Medicine and Dentistry, University of Aberdeen, AberdeenAB25 2ZD, UK.
authors.forename: Lewis D
authors.initials: LD
authors.lastname: Ritchie
authors.affiliation: RTI Health Solutions, Trav. Gracia 56, Atico 1, Barcelona 08006, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Perez-Gutthann
authors.affiliation: British Heart Foundation Cardiovascular Research Centre, University of Glasgow,126 University Place, GlasgowG12 8TA, UK.
authors.forename: Eugene
authors.initials: E
authors.lastname: Connolly
authors.affiliation: Robertson Centre for Biostatistics, University of Glasgow, Glasgow G12 8QQ, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Greenlaw
authors.affiliation: Medicines Monitoring Unit (MEMO), Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital & Medical School Dundee, Dundee DD1 9SY, UK.
authors.forename: Adam
authors.initials: A
authors.lastname: Wilson
authors.affiliation: Department of Practice and Policy, University College London, London WC1H 9JP, UK.
authors.forename: Li
authors.initials: L
authors.lastname: Wei
authors.affiliation: Medicines Monitoring Unit (MEMO), Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital & Medical School Dundee, Dundee DD1 9SY, UK.
authors.forename: Isla S
authors.initials: IS
authors.lastname: Mackenzie
mesh_terms: D054058:Acute Coronary Syndrome / Q000139:chemically induced / Q000453:epidemiology; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000453:epidemiology; D000068579:Celecoxib / Q000009:adverse effects*; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects*; D003718:Denmark / Q000453:epidemiology; D057915:Drug Substitution; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced / Q000453:epidemiology; D009426:Netherlands / Q000453:epidemiology; D010003:Osteoarthritis / Q000188:drug therapy / Q000453:epidemiology; D061214:Patient Safety; D010438:Peptic Ulcer Hemorrhage / Q000139:chemically induced; D011446:Prospective Studies; D020521:Stroke / Q000139:chemically induced / Q000453:epidemiology; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D000068579:Celecoxib
keywords: Arthritis; Cardiovascular; Celecoxib; NSAIDs