Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis
Key result
Celecoxib was noninferior to naproxen (HR 0.93; 95% CI 0.76-1.13) and ibuprofen (HR 0.85; 95% CI 0.70-1.04) for cardiovascular death, nonfatal MI, or nonfatal stroke (P<0.001 for noninferiority).
Why the study?
Does celecoxib prevent cardiovascular events compared to naproxen or ibuprofen in patients with arthritis at increased cardiovascular risk?
Population
24,081 patients requiring NSAIDs for osteoarthritis or rheumatoid arthritis who were at increased…
Comparison
Celecoxib for a mean treatment duration of… vs Naproxen or ibuprofen.
Design
RCT, randomly assigned
Follow-up
mean 34.1±13.4 months
Authors
Discussion
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Implication
Celecoxib may offer noninferior CV safety versus other NSAIDs; leaves open need for confirmatory trials before changing practice.
Key Points
- To evaluate the cardiovascular safety and noninferiority of celecoxib compared with naproxen or ibuprofen in patients with arthritis at increased cardiovascular risk.
- Randomized noninferiority trial (NCT00346216) enrolling 24,081 patients requiring NSAIDs for osteoarthritis or rheumatoid arthritis with heightened cardiovascular risk.
- Patients were randomly assigned to celecoxib (mean daily dose 209±37 mg), naproxen (852±103 mg), or ibuprofen (2045±246 mg), with a mean treatment duration of 20.3±16.0 months and follow-up of 34.1±13.4 months.
- The primary composite outcome was cardiovascular death (including hemorrhagic death), nonfatal myocardial infarction, or nonfatal stroke evaluated in intention-to-treat and on-treatment populations.
- In the intention-to-treat analysis, primary outcome events occurred in 2.3% (188/8,072) with celecoxib, 2.5% (201/8,040) with naproxen, and 2.7% (218/7,969) with ibuprofen (celecoxib vs. naproxen: HR 0.93, 95% CI 0.76–1.13; celecoxib vs. ibuprofen: HR 0.85, 95% CI 0.70–1.04; P<0.001 for noninferiority for both).
- In the on-treatment analysis, primary events occurred in 1.7% (134) with celecoxib, 1.8% (144) with naproxen, and 1.9% (155) with ibuprofen (celecoxib vs. naproxen: HR 0.90, 95% CI 0.71–1.15; celecoxib vs. ibuprofen: HR 0.81, 95% CI 0.65–1.02; P<0.001 for noninferiority for both).
- Gastrointestinal events were significantly lower with celecoxib than with naproxen (P=0.01) or ibuprofen (P=0.002), and renal events were significantly lower with celecoxib than with ibuprofen (P=0.004) but not naproxen (P=0.19).
Study Design
Type
RCT (n=24,081)
Randomization
randomly assigned
Structured PICO
Does celecoxib prevent cardiovascular events compared to naproxen or ibuprofen in patients with arthritis at increased cardiovascular risk?
P
Population
24,081 patients requiring NSAIDs for osteoarthritis or rheumatoid arthritis and at increased cardiovascular risk, followed for a mean of 34.1 months.
I
Intervention
Celecoxib (mean daily dose 209±37 mg) for a mean treatment duration of 20.3±16.0 months.
C
Comparator
Naproxen (mean daily dose 852±103 mg) or ibuprofen (mean daily dose 2045±246 mg).
O
Outcome
Composite outcome of cardiovascular death (including hemorrhagic death), nonfatal myocardial infarction, or nonfatal stroke.composite
Main Result
Hazard Ratio: 0.93 (95% CI 0.76–1.13)
Absolute Event Rate: 2.3% vs 2.5%
p-value: p=<0.001 for noninferiority
At moderate doses, celecoxib is noninferior to ibuprofen or naproxen regarding cardiovascular safety in arthritis patients at increased cardiovascular risk.
Limitations
- High rates of discontinuation: 68.8% of patients stopped taking the study drug, and 27.4% discontinued follow-up.
- 68.8% of patients stopped taking the study drug
- 27.4% of patients discontinued follow-up
Cite This Study
Nissen et al. (2016) conducted an RCT in Osteoarthritis or rheumatoid arthritis at increased cardiovascular risk (n=24,081). Celecoxib vs. Naproxen or Ibuprofen was evaluated on Cardiovascular death (including hemorrhagic death), nonfatal myocardial infarction, or nonfatal stroke (HR 0.93, 95% CI 0.76 to 1.13, p=<0.001 for noninferiority). Celecoxib was noninferior to naproxen (HR 0.93; 95% CI 0.76-1.13) and ibuprofen (HR 0.85; 95% CI 0.70-1.04) for cardiovascular death, nonfatal MI, or nonfatal stroke (P<0.001 for noninferiority).