Rofecoxib, selective COX-2 inhibitors and cardiovascular risk
Summary
The withdrawal of VIOXX, following concerns over a link with an increased risk of heart attack and stroke, was the largest prescription drug withdrawal in history. How early did its manufacturers and drug regulators know of the risks and how great are these risks? Dr Neeraj Dhaun, Dr Simon Maxwell and Prof David Webb review the evidence.
Key Points
- Conventional NSAIDs inhibit COX-1 and COX-2 isoenzymes which are involved in prostaglandin production.
- COX-2 inhibitors (coxibs), sub-class of NSAIDs, preferentially inhibit the COX-2 isoenzyme which predisposes the vascular system to hypertension, MI and stroke.
- Coxibs generally appear to increase the incidence of MI and stroke 3–4 fold when taken long-term, whereas they may reduce the frequency of gastrointestinal side-effects.
- Coxibs may provide better pain relief than NSAIDs in particular patients, but not in patients as whole.
- Patients at increased risk of vascular disease should not take coxibs, and other patients should take them on medical advice only.
- New independent agencies are needed to survey the long-term safety of drugs after they have been licensed.
Declaration of interests: N Dhaun and DJ Webb have no interests to declare. SRJ Maxwell has declared a non-personal interest whereby a colleague in his department was funded during their training by Roche and BMS; and a lapsed interest whereby seven years ago he was in receipt of funding for consultancy work from Astra Zeneca.
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