Randomized trial of switching from prescribed non-selective non-steroidal anti-inflammatory drugs to prescribed celecoxib: the Standard care vs. Celecoxib Outcome Trial (SCOT)

Thomas M MacDonald* (Corresponding Author), Chris J Hawkey, Ian Ford, John J V McMurray, James M Scheiman, Jesper Hallas, Evelyn Findlay, Diederick E Grobbee, F D Richard Hobbs, Stuart H Ralston, David M Reid, Matthew R Walters, John Webster, Frank Ruschitzka, Lewis D Ritchie, Susana Perez-Gutthann, Eugene Connolly, Nicola Greenlaw, Adam Wilson, Li WeiIsla S Mackenzie

*Corresponding author for this work

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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.

METHOD: 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).

INTERPRETATION: 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.

Original languageEnglish
Pages (from-to)1843-1850
Number of pages9
JournalEuropean Heart Journal
Volume38
Issue number23
Early online date4 Oct 2016
DOIs
Publication statusPublished - 14 Jun 2017

Bibliographical note

Acknowledgements

We would like to express our sincere gratitude to all the patients who participated in the study and all the doctors and nurses from each of the centres who contributed to the SCOT study. Recruiting Centres: Dundee: Wendy Saywood, Claudine Jennings, Alison McGinnis, Irene Donald, Emma Gellatly, Caroline Hall, Dawn Ross, Fiona Gowans, Kate Cowan, Wendy Urquhart, Patricia Robertson, Lesley Riley, Pamela Goodman, Moira Dryburgh, Johan McGill, Avril Donaldson. Aberdeen: Jacqueline Furnace, Joan Henderson, Frances Rentoul, Mandy Thompson, Emma Wilson, Heather Lawrence, Helen Keith, Julie Shotton. Edinburgh: Janet Thomson, Susan Begg, Julia Boyd, Theresa Harper, Guen Innes, Debra Kerr, Helen Reynolds, Lorraine Petrie, Janet Connelly, Morag McLean. Glasgow: Iain McInnes, Roger Sturrock, Linda Wilson, Geraldine Campbell, Rhona McKay, Kirsty Simpson, Joanne Flynn, Anne Benson, June Innes. Birmingham: Rachel Iles, Clare Taylor. Oxford: Ben Thompson, Sabrina Petersen, Pippa Whitbread, Marie-Lucie Gibbons, Mina Davoudianfar, Faye Alexander. Nottingham: Jen Dumbleton, Diane Stevenson, Vic Shepherd, David Goddard, Angela Andrew, Alice Cotton. Denmark: Michael Dall, Kasper Soltoft Larsen; Morten Rix Hansen, Viv Toft Lie, Ellen Kathrine Arve, Anita Hagelskaer, Susanne Leed Henriksen, Charlotte Enok Poulsen, Trine Ammentorp Gregersen, Birgith Kjaergaard, Dorthe Karup Holm, Brit Jorgensen, Anja Holmgaard, Vibeke Karlsen, Birgitte Vajsbaek. Amsterdam: Nils Visser, Helen van den Heuvel, Astrid Suiker, Nathalie Groetelaers, Aline Veurink-Westrik.

Funding

An unrestricted Investigator Initiated Research Grant from Pfizer USA to the University of Dundee. The University of Dundee was the legal sponsor of the study (responsible for all aspects of the trial). Some of the funding received from Pfizer USA went towards salaries for Dundee staff (TMM, IM AW, EF) and staff at other Universities. The University of Dundee disbursed study funding to all other investigator institutions so, for example, IF received research funding for the SCOT study indirectly from Pfizer (via the University of Dundee) as did other investigators. F.D.R.H. is partially supported by NIHR School for Primary Care Research, NIHR CLAHRC Oxford, NIHR Oxford BRC and Harris Manchester College, Oxford.

Keywords

  • NSAIDs
  • Celecoxib
  • Cardiovascular
  • Arthritis

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