COX-2 inhibitors and the cardiovascular system

Area of Science:

• Pharmacology
• Cardiovascular Medicine
• Gastroenterology

Background:

• Cyclooxygenase-2 selective inhibitors (coxibs) are a novel class of NSAIDs targeting COX-2, implicated in inflammatory prostanoid production.
• Clinical trials have yielded divergent cardiovascular event rates for coxibs, necessitating a review of their pharmacology and trial designs.

Purpose of the Study:

• To review the differing cardiovascular event rates from the VIGOR and CLASS trials of coxibs.
• To contextualize these findings within current clinical and basic pharmacology of coxibs.

Main Methods:

• Review of data from the Vioxx Gastrointestinal Outcomes Research Trial (VIGOR) and the Celecoxib Long-term Arthritis Safety Study (CLASS).
• Analysis of cardiovascular and gastrointestinal endpoints in patients receiving coxibs versus comparator drugs (naproxen, non-selective NSAIDs).

Main Results:

• The VIGOR trial showed a higher incidence of cardiovascular events with rofecoxib compared to naproxen.
• The CLASS trial found no significant difference in cardiovascular events between celecoxib and NSAID comparators.
• Gastrointestinal outcomes favored rofecoxib in VIGOR, but celecoxib showed no significant GI benefit over NSAIDs in CLASS.

Conclusions:

• Cardiovascular outcomes in VIGOR may be attributed to chance, naproxen's effect, or differential prostacyclin/thromboxane inhibition by rofecoxib.
• Differences between trials could stem from chance, trial design (e.g., aspirin use), or intrinsic coxib pharmacology.
• While combining aspirin with rofecoxib might reduce GI events, coxib use alone does not warrant initiating cardioprotective aspirin therapy.