Randomised trial of switching from prescribed non-selective non-steroidal anti-inflammatory drugs to prescribed celecoxib: The Standard care versus Celecoxib Outcome Trial (SCOT)

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

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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 cardiovascular safety of switching to celecoxib versus continuing nsNSAID therapy in a European setting.

Method: Patients aged 60 years and over with osteoarthritis or rheumatoid arthritis, free from established cardiovascular (CV) disease and taking chronic prescribed nsNSAIDs, were randomised to switch to celecoxib or to continue their previous nsNSAID. The primary endpoint was hospitalisation 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.

Results: 7,297 participants were randomised. During a median 3 years 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 (hazard ratio = 1.12, 95% confidence interval, 0.81 to 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 (hazard ratio 1.04; 95% confidence interval, 0.81 to 1.33; p = 0.75). Pre-specified non-inferiority was achieved in the intention-to-treat analysis. The upper bound of the 95% confidence limit for the absolute increase in OT risk associated with celecoxib treatment was 2 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 ARs and haematological ARs 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 cardiovascular disease and taking prescribed chronic nsNSAIDs, cardiovascular events were infrequent and similar on celecoxib and nsNSAIDs. There was no advantage of a strategy of switching prescribed nsNSAIDs to prescribed celecoxib. The present study excluded an increased risk of the primary endpoint of more than 2 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

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Celecoxib
Anti-Inflammatory Agents
Pharmaceutical Preparations
Cardiovascular Diseases
Myocardial Infarction
Confidence Intervals

Keywords

  • NSAIDs
  • Celecoxib
  • Cardiovascular
  • Arthritis

Cite this

MacDonald, Thomas ; Hawkey, Christopher J. ; Ford, Ian ; McMurray, John J. V. ; Scheiman, James M. ; Hallas, Jesper ; Findlay, Evelyn ; Grobbee, Diederick E. ; Hobbs, FD Richard ; Ralston, Stuart H. ; Reid, David M. ; Walters, Matthew ; Webster, John ; Ruschitzka, Frank ; Ritchie, Lewis D. ; Perez-Gutthann, Susana ; Connolly, Eugene ; Greenlaw, Nicola ; Wilson, Adam ; Wei, Li ; Mackenzie, Isla. / Randomised trial of switching from prescribed non-selective non-steroidal anti-inflammatory drugs to prescribed celecoxib : The Standard care versus Celecoxib Outcome Trial (SCOT). In: European Heart Journal. 2017 ; Vol. 38, No. 23. pp. 1843-1850.
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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 cardiovascular safety of switching to celecoxib versus continuing nsNSAID therapy in a European setting.Method: Patients aged 60 years and over with osteoarthritis or rheumatoid arthritis, free from established cardiovascular (CV) disease and taking chronic prescribed nsNSAIDs, were randomised to switch to celecoxib or to continue their previous nsNSAID. The primary endpoint was hospitalisation 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. Results: 7,297 participants were randomised. During a median 3 years 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 (hazard ratio = 1.12, 95{\%} confidence interval, 0.81 to 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 (hazard ratio 1.04; 95{\%} confidence interval, 0.81 to 1.33; p = 0.75). Pre-specified non-inferiority was achieved in the intention-to-treat analysis. The upper bound of the 95{\%} confidence limit for the absolute increase in OT risk associated with celecoxib treatment was 2 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 ARs and haematological ARs 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 cardiovascular disease and taking prescribed chronic nsNSAIDs, cardiovascular events were infrequent and similar on celecoxib and nsNSAIDs. There was no advantage of a strategy of switching prescribed nsNSAIDs to prescribed celecoxib. The present study excluded an increased risk of the primary endpoint of more than 2 events per 1000 patient-years associated with switching to prescribed celecoxib.",
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author = "Thomas MacDonald and Hawkey, {Christopher J.} and Ian Ford and McMurray, {John J. V.} and Scheiman, {James M.} and Jesper Hallas and Evelyn Findlay and Grobbee, {Diederick E.} and Hobbs, {FD Richard} and Ralston, {Stuart H.} and Reid, {David M.} and Matthew Walters and John Webster and Frank Ruschitzka and Ritchie, {Lewis D.} and Susana Perez-Gutthann and Eugene Connolly and Nicola Greenlaw and Adam Wilson and Li Wei and Isla Mackenzie",
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MacDonald, T, Hawkey, CJ, Ford, I, McMurray, JJV, Scheiman, JM, Hallas, J, Findlay, E, Grobbee, DE, Hobbs, FDR, Ralston, SH, Reid, DM, Walters, M, Webster, J, Ruschitzka, F, Ritchie, LD, Perez-Gutthann, S, Connolly, E, Greenlaw, N, Wilson, A, Wei, L & Mackenzie, I 2017, 'Randomised trial of switching from prescribed non-selective non-steroidal anti-inflammatory drugs to prescribed celecoxib: The Standard care versus Celecoxib Outcome Trial (SCOT)', European Heart Journal, vol. 38, no. 23, pp. 1843-1850. https://doi.org/10.1093/eurheartj/ehw387

Randomised trial of switching from prescribed non-selective non-steroidal anti-inflammatory drugs to prescribed celecoxib : The Standard care versus Celecoxib Outcome Trial (SCOT). / MacDonald, Thomas (Lead / Corresponding author); Hawkey, Christopher J.; Ford, Ian; McMurray, John J. V.; Scheiman, James M.; Hallas, Jesper; Findlay, Evelyn; Grobbee, Diederick E.; Hobbs, FD Richard; Ralston, Stuart H.; Reid, David M.; Walters, Matthew; Webster, John; Ruschitzka, Frank; Ritchie, Lewis D.; Perez-Gutthann, Susana; Connolly, Eugene; Greenlaw, Nicola; Wilson, Adam; Wei, Li; Mackenzie, Isla.

In: European Heart Journal, Vol. 38, No. 23, 14.06.2017, p. 1843-1850.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Randomised trial of switching from prescribed non-selective non-steroidal anti-inflammatory drugs to prescribed celecoxib

T2 - The Standard care versus Celecoxib Outcome Trial (SCOT)

AU - MacDonald, Thomas

AU - Hawkey, Christopher J.

AU - Ford, Ian

AU - McMurray, John J. V.

AU - Scheiman, James M.

AU - Hallas, Jesper

AU - Findlay, Evelyn

AU - Grobbee, Diederick E.

AU - Hobbs, FD Richard

AU - Ralston, Stuart H.

AU - Reid, David M.

AU - Walters, Matthew

AU - Webster, John

AU - Ruschitzka, Frank

AU - Ritchie, Lewis D.

AU - Perez-Gutthann, Susana

AU - Connolly, Eugene

AU - Greenlaw, Nicola

AU - Wilson, Adam

AU - Wei, Li

AU - Mackenzie, Isla

PY - 2017/6/14

Y1 - 2017/6/14

N2 - 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 cardiovascular safety of switching to celecoxib versus continuing nsNSAID therapy in a European setting.Method: Patients aged 60 years and over with osteoarthritis or rheumatoid arthritis, free from established cardiovascular (CV) disease and taking chronic prescribed nsNSAIDs, were randomised to switch to celecoxib or to continue their previous nsNSAID. The primary endpoint was hospitalisation 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. Results: 7,297 participants were randomised. During a median 3 years 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 (hazard ratio = 1.12, 95% confidence interval, 0.81 to 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 (hazard ratio 1.04; 95% confidence interval, 0.81 to 1.33; p = 0.75). Pre-specified non-inferiority was achieved in the intention-to-treat analysis. The upper bound of the 95% confidence limit for the absolute increase in OT risk associated with celecoxib treatment was 2 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 ARs and haematological ARs 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 cardiovascular disease and taking prescribed chronic nsNSAIDs, cardiovascular events were infrequent and similar on celecoxib and nsNSAIDs. There was no advantage of a strategy of switching prescribed nsNSAIDs to prescribed celecoxib. The present study excluded an increased risk of the primary endpoint of more than 2 events per 1000 patient-years associated with switching to prescribed celecoxib.

AB - 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 cardiovascular safety of switching to celecoxib versus continuing nsNSAID therapy in a European setting.Method: Patients aged 60 years and over with osteoarthritis or rheumatoid arthritis, free from established cardiovascular (CV) disease and taking chronic prescribed nsNSAIDs, were randomised to switch to celecoxib or to continue their previous nsNSAID. The primary endpoint was hospitalisation 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. Results: 7,297 participants were randomised. During a median 3 years 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 (hazard ratio = 1.12, 95% confidence interval, 0.81 to 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 (hazard ratio 1.04; 95% confidence interval, 0.81 to 1.33; p = 0.75). Pre-specified non-inferiority was achieved in the intention-to-treat analysis. The upper bound of the 95% confidence limit for the absolute increase in OT risk associated with celecoxib treatment was 2 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 ARs and haematological ARs 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 cardiovascular disease and taking prescribed chronic nsNSAIDs, cardiovascular events were infrequent and similar on celecoxib and nsNSAIDs. There was no advantage of a strategy of switching prescribed nsNSAIDs to prescribed celecoxib. The present study excluded an increased risk of the primary endpoint of more than 2 events per 1000 patient-years associated with switching to prescribed celecoxib.

KW - NSAIDs

KW - Celecoxib

KW - Cardiovascular

KW - Arthritis

U2 - 10.1093/eurheartj/ehw387

DO - 10.1093/eurheartj/ehw387

M3 - Article

C2 - 27705888

VL - 38

SP - 1843

EP - 1850

JO - European Heart Journal

JF - European Heart Journal

SN - 0195-668X

IS - 23

ER -