Cardiovascular risk of celecoxib in 6 randomized placebo-controlled trials: the cross trial safety analysis

Scott D Solomon ¹, Janet Wittes , Peter V Finn

⁰Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA. ssolomon@rics.bwh.harvard.edu

Circulation +

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April 2, 2008

View abstract on PubMed

Summary

Cardiovascular risk increases with celecoxib dose, with the highest risk at 400 mg BID. Patients with higher baseline cardiovascular risk experienced disproportionately greater adverse events with celecoxib.

Area Of Science

Cardiology
Pharmacology
Clinical Trials

Background

Previous studies indicated increased cardiovascular risk with cyclooxygenase-2 inhibitors.
Limited data existed on celecoxib dose or baseline cardiovascular status effects on risk.

Purpose Of The Study

To assess cardiovascular risk associated with celecoxib across three dose regimens.
To evaluate the relationship between baseline cardiovascular risk and celecoxib's effect on cardiovascular events.

Main Methods

Patient-level pooled analysis of data from 6 placebo-controlled trials.
Included 7950 patients with planned follow-up of at least 3 years.
Assessed celecoxib doses of 400 mg QD, 200 mg BID, and 400 mg BID.

Main Results

A pooled hazard ratio of 1.6 (95% CI, 1.1 to 2.3) for the composite endpoint was observed.
Cardiovascular risk increased significantly with celecoxib dose (P=0.0005).
Highest risk was associated with the 400 mg BID dose (HR, 3.1; 95% CI, 1.5 to 6.1), and lowest with 400 mg QD (HR, 1.1; 95% CI, 0.6 to 2.0).
Patients with higher baseline cardiovascular risk showed disproportionately greater celecoxib-related adverse events (P for interaction=0.034).

Conclusions

Evidence suggests differential cardiovascular risk based on celecoxib dose and patient's baseline cardiovascular risk.
Findings may aid in guiding treatment decisions for patients benefiting from selective cyclooxygenase-2 inhibition.

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