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The results of a clinical trial (PRECISION)1 comparing the cardiovascular safety of the COX-2 selective NSAID celecoxib (Celebrex, and generics) with that of ibuprofen and naproxen, which are nonselective, have been described in the lay press in terms that may overestimate the safety of celecoxib.
NSAID PHARMACOLOGY — NSAIDs inhibit the enzyme cyclooxygenase (COX), which is required for synthesis of prostaglandins and thromboxane. COX-1 inhibition blocks the protective effect of prostaglandins on the gastric mucosa, which can cause gastrointestinal toxicity, and has an antiplatelet effect that can cause bleeding. COX-2 inhibition produces therapeutic anti-inflammatory and analgesic effects, but it has effects on vascular endothelium that can be prothrombotic.
Ibuprofen and naproxen inhibit COX-1 more than COX-2. The COX-2 selective NSAID rofecoxib (Vioxx),... more
- SE Nissen et al. Cardiovascular safety of celecoxib, naproxen, or ibuprofen for arthritis. N Engl J Med 2016 Nov 13 (epub).
- JM Wright. The double-edged sword of COX-2 selective NSAIDs. CMAJ 2002; 167:1131.
- SD Solomon et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 2005; 352:1071.
- MA Perazella. COX-2 selective inhibitors: analysis of the renal effects. Expert Opin Drug Saf 2002; 1:53.
- GA FitzGerald. ImPRECISION: Limitations to interpretation of a large randomized clinical trial. Circulation 2016 Nov 13 (epub).