article91

PRECISION

"Celecoxib vs. Ibuprofen or Naproxen in Patients with Increased Cardiovascular Risk".The New England Journal of Medicine. 2016.

Clinical Question

Does moderate-dose celecoxib have similar cardiovascular safety compared to ibuprofen or naproxen in patients with osteoarthritis or rheumatoid arthritis who are at increased cardiovascular risk?

Bottom Line

Moderate-dose celecoxib was noninferior to ibuprofen or naproxen with regard to cardiovascular safety in patients requiring NSAIDs for osteoarthritis or rheumatoid arthritis and at increased cardiovascular risk.

Major Points

Guidelines

Design

- Multicenter, double-blind, randomized, noninferiority trial
- N=24,081 patients
- Celecoxib group (mean daily dose, 209 mg)
- Naproxen group (mean daily dose, 852 mg)
- Ibuprofen group (mean daily dose, 2045 mg)
- Mean follow-up: 34.1 months

Population

- Patients 18 years or older requiring daily NSAIDs for osteoarthritis or rheumatoid arthritis and with established cardiovascular disease or increased risk of cardiovascular disease.

Interventions

- Celecoxib (100 mg twice daily), ibuprofen (600 mg three times daily), or naproxen (375 mg twice daily) with matching placebo.

Outcomes

- Primary Outcomes: Composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.
- Secondary Outcomes: Major adverse cardiovascular events, gastrointestinal events, and renal outcomes.
- Tertiary Outcomes: Clinically significant renal events, iron deficiency anemia of gastrointestinal origin, and hospitalization for heart failure or hypertension.

Criticisms

- Lower adherence and retention might have influenced the principal conclusions, though similarity in intention-to-treat and on-treatment populations suggests the primary findings were likely unaffected.
- Multiplicity of comparisons without adjustment increases the potential for false positives.
- No insights can be provided regarding over two dozen other marketed NSAIDs, as the results only reflect the relative safety of the three drugs in the trial.

Funding

The study was funded by Pfizer.