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Celecoxib increases cardiovascular risk in dose-, regimen-related fashion

Thursday, April 03 2008 | Comments

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What's This? By Nancy Stanley

Patients who receive celecoxib have an increased cardiovascular risk relative to patients who receive placebo, and the risk may vary based on the dose and dose regimen of celecoxib, new data show.

Researchers performed a meta-analysis of 6 randomized, double-blind trials that compared celecoxib with placebo for treating conditions other than arthritis and had a planned follow-up of >=3 years. In the studies, 7,950 patients received celecoxib 400 mg once daily, celecoxib 200 mg twice daily, or celecoxib 400 mg twice daily. A total of 16,070 patient-years of follow-up were included in the analysis.

The patients were stratified by baseline cardiovascular risk as low risk, moderate risk, or high risk. The primary endpoint of the current analysis was the combination of cardiovascular death, myocardial infarction, stroke, heart failure, or a thromboembolic event.

The overall pooled hazard ratio for the composite endpoint was 1.6 (95% CI, 1.1-2.3).

For the patients who received celecoxib 400 mg once daily, the pooled HR for the primary endpoint was 1.1 (95% CI, 0.6-2.0). For the patients who received celecoxib 200 mg twice daily, the pooled HR was 1.8 (95% CI, 1.1-3.1), while the pooled HR was 3.1 (95% CI, 1.5-6.1) for the patients who received celecoxib 400 mg twice daily. This resulted in a significant dose-regimen effect (P=.0005 for trend).

The overall event rate increased across the 3 baseline risk categories, regardless of celecoxib dose. There was a doubling of risk between the low- and moderate-risk groups and a further doubling of risk between the moderate- and high-risk groups.

Low-risk patients had the least effective dose, while high-risk patients had the greatest effective dose.  

"Both the relative and the absolute risks increased in the higher baseline risk category," Dr. Scott Solomon, lead researcher, said.

He noted that none of the trials were designed or powered to assess cardiovascular risk and that all of the doses tested were higher than the doses typically used in patients with osteoarthritis.

"These data may provide a measure of comfort in prescribing celecoxib in patients with very low baseline cardiovascular risk, but would argue for caution in prescribing celecoxib in patients with high baseline risk," Dr. Solomon concluded. (Presentation 407-6.)

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