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

MacDonald, T. M. et al. (2017) Randomized trial of switching from prescribed non-selective non-steroidal anti-inflammatory drugs to prescribed celecoxib: the Standard care vs. Celecoxib Outcome Trial (SCOT). European Heart Journal, 38(23), pp. 1843-1850. (doi: 10.1093/eurheartj/ehw387) (PMID:27705888) (PMCID:PMC5837371)

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.

• Item Type: Articles
• Additional Information: 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.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Greenlaw, Miss Nicola and McMurray, Professor John and Ford, Professor Ian and Walters, Professor Matthew
• Authors: MacDonald, T. M., Hawkey, C. J., Ford, I., McMurray, J. J.V., Scheiman, J. M., Hallas, J., Findlay, E., Grobbee, D. E., Hobbs, F.D. R., Ralston, S. H., Reid, D. M., Walters, M. R., Webster, J., Ruschitzka, F., Ritchie, L. D., Perez-Gutthann, S., Connolly, E., Greenlaw, N., Wilson, A., Wei, L., and Mackenzie, I. S.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: European Heart Journal
• Publisher: Oxford University Press
• ISSN: 0195-668X
• ISSN (Online): 1522-9645
• Published Online: 04 October 2016
• Copyright Holders: Copyright © 2016 The Authors
• First Published: First published in European Heart Journal 38(23):1843-1850
• Publisher Policy: Reproduced under a Creative Commons License