Prospective Randomized Evaluation of Celeboxib Integrated Safety Versus Ibuprofen or Naproxen - PRECISION

Contribution To Literature:

The PRECISION trial showed similar cardiovascular safety of celecoxib compared with ibuprofen or naproxen.

Description:

The goal of the trial was to evaluate the cardiovascular safety of celecoxib compared with ibuprofen or naproxen among patients with arthritis and increased cardiovascular risk requiring treatment with a nonsteroidal anti-inflammatory drug (NSAID).

Study Design

  • Randomized
  • Parallel
  • Blinded
  • Stratified

Patients with arthritis and increased cardiovascular risk were randomized to celecoxib 100 mg twice daily (n = 8,072) versus ibuprofen 600 mg three times daily (n = 8,040) versus naproxen 375 mg twice daily (n = 7,969). Patients with rheumatoid arthritis could up-titrate their study medication if needed at follow-up visit (celecoxib 200 mg twice daily, ibuprofen 800 mg three times daily, or naproxen 500 mg twice daily).

  • Total number of enrollees: 24,081
  • Duration of follow-up: mean 34 months (mean treatment duration 20 months)
  • Mean patient age: 63 years
  • Percentage female: 64%
  • Percentage with diabetes: 35%

Inclusion criteria:

  • Patients ≥18 years of age with osteoarthritis or rheumatoid arthritis requiring treatment with a NSAID
  • Established cardiovascular disease or increased risk for cardiovascular disease

Exclusion criteria:

  • Patients whose arthritis pain was managed adequately with acetaminophen

Other salient features/characteristics:

  • Patient risk category (primary prevention 77%, secondary prevention 23%)
  • During follow-up, 69% of patients stopped study drug

Principal Findings:

The primary outcome, incidence of cardiovascular death, myocardial infarction, or stroke, occurred in 2.3% of the celecoxib group vs. 2.7% of the ibuprofen group vs. 2.5% of the naproxen group (hazard ratio [HR] 0.85, pnoninferiority < 0.001 for celecoxib vs. ibuprofen; HR 0.93, pnoninferiority < 0.001 for celecoxib vs. naproxen; HR 1.08, pnoninferiority = 0.02 for ibuprofen vs. naproxen). Findings were the same with subgroup analysis and on-treatment analysis.

Secondary outcomes:

  • Gastrointestinal  (GI) events: 1.1% for celecoxib, 1.6% for ibuprofen, 1.5% for naproxen (HR 0.65, p = 0.002 for celecoxib vs. ibuprofen, HR 0.71, p = 0.01 for celecoxib vs. naproxen)
  • Renal events: 0.7% for celecoxib, 1.1% for ibuprofen, 0.9% for naproxen (HR 0.61, p = 0.004 for celecoxib vs. ibuprofen, HR = 0.79, p = 0.19 for celecoxib vs. naproxen)

Interpretation:

Among patients with arthritis (osteoarthritis or rheumatoid arthritis) and increased cardiovascular risk, modest-dose celecoxib was noninferior to ibuprofen or naproxen in regard to cardiovascular safety. Secondary findings documented fewer GI events compared with ibuprofen or naproxen, and fewer renal events compared with ibuprofen. Limitations of the trial include very high study discontinuation (69%) and an overall low event rate (77% did not have established cardiovascular disease).

A second important finding of the trial is dispelling the notion that naproxen is the safest nonselective NSAID. This trial demonstrated similar overall cardiovascular events for ibuprofen versus naproxen.

References:

Nissen SE, Yeomans ND, Solomon DH, et al., on behalf of the PRECISION Trial Investigators. Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis. N Engl J Med 2016;375:2519-29.

Editorial: FitzGerald GA. Imprecision: Limitations to Interpretation of a Large Randomized Clinical Trial. Circulation 2017;135:113-15.

Presented by Dr. Steven E. Nissen at the American Heart Association Annual Scientific Sessions (AHA 2016), New Orleans, LA, November 13, 2016.

Clinical Topics: Acute Coronary Syndromes, Prevention, Stable Ischemic Heart Disease, Chronic Angina

Keywords: Acute Coronary Syndrome, AHA Annual Scientific Sessions, Angina, Stable, Anti-Inflammatory Agents, Non-Steroidal, Arthritis, Rheumatoid, Cardiovascular Diseases, Cyclooxygenase Inhibitors, Gastrointestinal Tract, Ibuprofen, Myocardial Infarction, Naproxen, Osteoarthritis, Primary Prevention, Pyrazoles, Renal Insufficiency, Risk Factors, Stroke


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