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.