- Prescribing of celecoxib has fallen dramatically in the UK since the withdrawal of rofecoxib from the market.
- There has been recent concern about the cardiovascular safety of COX-2 inhibitors.
What is the evidence?
- The APPROVe study led to the withdrawal of rofecoxib because the incidence of cardiovascular events was double with rofecoxib compared to placebo (N Eng J Med 2005; 352: 1,092).
- The APC trial found that compared to placebo, celecoxib was associated with an excess of cardiovascular events, with a dose-related increase in risk (N Eng J Med 2005; 352: 1,071).
- In contrast, a pooled analysis of the cardiovascular safety of several COX-2 inhibitors in a high-risk population did not provide any evidence of an increased risk (Arch Intern Med 2005; 165: 181).
- A recent meta-analysis has shown that COX-2 inhibitors and high-dose traditional NSAIDs are associated with a moderate increased risk of vascular events (BMJ 2006; 332: 1,302–5).
- A meta-analysis of four trials comparing celecoxib with placebo found that the odds ratio of MI compared to placebo was 2.2 (J R Soc Med 2006; 99: 132).
- A UK study of primary care patients has shown that there is no evidence that COX-2 inhibitors are more GI protective than NSAIDs (BMJ 2005; 331: 1,310).
Implications for practice
- Most data suggest that conventional NSAIDs have no impact on the risk of cardiovascular events. Conventional NSAIDs may even be cardioprotective (Br J Cardiol 2005; 12: 387).
- Paracetamol offers an effective and safe treatment for generalised musculoskeletal pain (Cochrane Database Syst Rev 2006;(1): CD004257).
- One meta-analysis has shown that the combination of NSAIDs with proton-pump inhibitors seems to be less likely to cause dyspepsia in patients with arthritis than COX-2 inhibitors (Am J Med 2006; 119: 448).
- The MHRA recommend avoiding treatment with COX-2 inhibitors in patients with known IHD.
- The European Medicines Agency (EMEA) has decided that the benefit-risk balance of NSAIDs remains favourable.
- NICE recommends the use of COX-2 inhibitors for arthritis.
Medicines and Healthcare Products Regulatory Agency
European Medicines Agency
- Dr Louise Newson is a GP in the West Midlands and author of ‘Hot Topics for MRCGP and General Practitioners’, PasTest 2006