Prescribing COX-2 inhibitors

Current situation

  • 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).

Available guidelines

  • 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.

Useful websites

NICE

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

Have you registered with us yet?

Register now to enjoy more articles and free email bulletins

Register

Already registered?

Sign in

Follow Us:

Just published

Whitehall street sign

NHS officials doubled in two years as GP workforce dropped

Staff employed by NHS England and the DHSC doubled in two years from the start of...

Child coughing

NICE traffic light tool that helps GPs spot seriously ill under-5s 'unreliable'

NICE's 'traffic light' system - intended to help GPs identify risk of serious illness...

Pregnant woman receives COVID-19 vaccine

COVID-19 vaccine uptake in pregnant women rising but stark inequality remains

More than half of pregnant women are now double vaccinated against COVID-19 as uptake...

Vaccination tracker

UK COVID-19 vaccination programme tracker

GPs across the UK have led the largest-ever NHS vaccination programme in response...

GMC sign

Overseas-graduate GPs fare worse in medical tribunals due to lack of legal help

UK GPs who graduated overseas face worse outcomes in GMC cases because they are far...

Woman using HRT patch

Practical advice for GPs on prescribing HRT

GP menopause specialists Dr Louise Newson and Dr Olivia Jones provides an overview...