The Pharmaceutical Journal
Vol 277 No 7419 p361
23 September 2006

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Diclofenac may share CV risks of COX-2 inhibitors

Diclofenac seems to share the increased cardiovascular risks seen with selective cyclo-oxygenase-2 inhibitors, according to the authors of a systematic review, published online on 12 September 2006 (JAMA).

The review of 17 case-control and six cohort studies examined the risks of serious cardiovascular events for individual non-steroidal anti-inflammatory drugs and selective COX-2 inhibitors. The results confirm an increased, dose-related risk with rofecoxib (relative risk 2.19, 95 per cent confidence interval 1.64–2.91 for doses over 25mg per day), a risk that was evident during the first month of treatment.

Celecoxib was not associated with an elevated risk at a dose of 200mg per day, however, the possibility of an increased risk at higher doses is not excluded, say the researchers.

Among the NSAIDs, the highest risk was seen with diclofenac (1.40, 1.16–1.70). The other drugs had risks close to one: naproxen (0.97, 0.87–1.07); piroxicam (1.06, 0.70–1.59); and ibuprofen (1.07, 0.97–1.18).

The researchers say that diclofenac appears to be harmful at commonly used doses and call for a review of its regulatory status.

A second review (ibid) of 114 randomised controlled trials with 116,094 participants investigated the risks of renal events and arrhythmias with COX-2 inhibitors. The results suggest that rofecoxib is associated with an increased risk of renal events (1.53, 1.33–1.76) and arrhythmias (2.90, 1.07–7.88); the risks increase with greater dose and duration. A class effect for COX-2 inhibitors was not observed.

The author of an accompanying editorial (ibid) suggests that for most patients who require chronic pain relief, naproxen appears to be the safest NSAID choice from a cardiovascular perspective. For those at high risk of gastrointestinal-related side effects, naproxen plus a proton pump inhibitor is less costly, and probably safer, than prescribing low-dose celecoxib, he says. “Additional studies exploring the benefits and risks of this approach are urgently needed,” he adds.