Session Type: ACR Late-breaking Abstract Session
Session Time: 4:30PM-6:00PM
*Both authors (Husni, Solomon) contributed equally and will co present
Background/Purpose: The relative cardiovascular (CV) safety of non-selective NSAIDs and selective COX-2 NSAIDs remains unclear. Given the chronic use of NSAIDs in the osteoarthritis (OA) and rheumatoid arthritis (RA) population along with known concomitant risk for CV disease, the relative safety of these agents is of critical importance for rheumatologists and their patients. The best opportunity to answer this question is to conduct a very large randomized controlled trial (RCT) that directly and prospectively compares the CV safety of these agents, the PRECISION trial.
Methods: PRECISION was a double blind and triple dummy RCT conducted worldwide. Subjects enrolled in PRECISION had to have a known history of CV events (myocardial infarction, stroke, or coronary re-vascularization) or evidence of CV risk based on traditional CV risk factors. Additional criteria included a physician diagnosis of OA or RA, daily need for NSAID therapy, no CV events within the last 90 days and no contraindications to the use of these agents. Subjects were randomized to celecoxib 100-200mg bid, ibuprofen 600-800mg tid, or naproxen 375-500mg bid. All subjects were provided open-label esomeprazole at 20-40mg qd and aspirin was allowed as part of standard of care if applicable. The primary CV outcome was a composite of CV death (including hemorrhagic), non-fatal MI, and non-fatal stroke with at least 18 months of follow-up. The study was designed as a non-inferiority trial with the main hypothesis that CV risk among subjects randomized to celecoxib would have an upper confidence interval (CI) of ≤ 1.33 for the intention to treat (ITT) and a HR ≤ 1.12 with an upper CI of ≤ 1.40 for the on treatment population compared with naproxen or ibuprofen based on a one-sided confidence interval of 97.5%. The trial continued for 10 years until the required 580 CV events for 30 months ITT analysis and 420 events for 42 months on-treatment population analysis were observed. Additional measures of function, global arthritis activity, and VAS pain were recorded.
The trial enrolled patients from 13 countries, with 923 sites, and 80% of subjects came from the US. A total of 24,081 subjects were enrolled and included in the final analyses, with 90% having OA and 10% RA. The mean age of subjects with OA was 63.5 years and for RA 60.7 years; 63.1% of subjects with OA were female and 73.2% with RA were female. The age and gender distribution did not differ by NSAID treatment assignment. Adherence was 80% over at least 6-months of follow-up, with a median follow-up of 18 months. The comparative CV risk by NSAID treatment arm will be presented separately for subjects with OA and RA. Gastrointestinal (GI) and renal adverse events were also adjudicated and will be presented for subjects with OA and RA by treatment arm.
Conclusion: PRECISION represents the largest CV safety trial of commonly used NSAIDs among patients with OA or RA. The results to be presented will clarify whether these NSAIDs carry the same CV, GI and renal risk across OA and RA patients.
Disclosure: M. E. Husni, Lilly, Novartis, Abbvie, Celgene, Bristol Myers Squibb, Amgen, Janssen, & UCB pharma, 5,Pfizer Inc, 6; D. H. Solomon, Pfizer Inc, 2,Pfizer Inc, 6; K. E. Wolski, None; L. M. Wisniewski, Pfizer Inc, 2; S. E. Nissen, Pfizer Inc, 2.
To cite this abstract in AMA style:Husni ME, Solomon DH, Wolski KE, Wisniewski LM, Nissen SE. The Cardiovascular Safety of Celecoxib Versus Ibuprofen or Naproxen in 24,081 Patients with Osteoarthritis or Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). http://acrabstracts.org/abstract/the-cardiovascular-safety-of-celecoxib-versus-ibuprofen-or-naproxen-in-24081-patients-with-osteoarthritis-or-rheumatoid-arthritis/. Accessed August 19, 2017.
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