Aimee Lettis from the GP Update team gives us short, sharp nuggets of clinical information for sessional GPs.

They’re one of the commonest painkillers used in primary care. But if, like me, you’re always slightly anxious about prescribing an NSAID, you may find this review on NSAIDS useful. First though, here’s a warning about diclofenac for those still prescribing it. 

Drug Safety Update on diclofenac

Following a recent Europe-wide review of the cardiovascular safety of diclofenac, the MHRA has made new recommendations about prescribing oral (not topical) diclofenac (Drug Safety Update 2013;6(11):2).

Patients with these conditions should be switched to an alternative at the next available routine visit. They advise naproxen (≤750mg/day) or ibuprofen (≤1200mg/day) as first-line because these have the best cardiovascular risk profiles.

We should also be careful using diclofenac in at-risk groups:

  • Smokers
  • Hypertensives
  • Patients with hyperlipidaemia
  • Diabetics

This BMJ Review gives an excellent overview of the harms and benefits of NSAIDs (BMJ 2013;346:f3195). Here, we concentrate on the harms.

Cardiovascular harms

All NSAIDs, with the apparent exception of naproxen, increase the risk of myocardial infarction and coronary death. Many RCTs and meta-analyses have also shown an increased stroke risk, although the latest meta-analysis did not.

Remember, NSAIDs block the protective effect of aspirin so co-prescription should be avoided where possible. The exceptions are COX-2 inhibitors and diclofenac (given 2 hours after aspirin) but we wouldn’t prescribe these to someone needing aspirin anyway because of the cardiovascular risk!

Gastrointestinal harms

All NSAIDs are associated with an increased risk of upper GI bleeds, with a NNH of 50-60/year for an additional bleed. The risk with COX-2 inhibitors is lower but the extra risk may be reduced by giving a proton-pump inhibitor(PPI) (Lancet 2010;376:173). The authors advise if NSAID prescribing is essential then we should consider a PPI in all but particularly the high-risk groups:

  • Long-term use
  • >65y
  • Previous peptic ulcer/bleed
  • SSRI/aspirin/steroid/anticoagulant use
  • High alcohol intake
  • Cardiac/renal/liver impairment

Renal harms

All NSAIDs can cause deterioration in renal function, particularly in those on angiotensin-converting enzyme inhibitors(ACEI) or angiotension-receptor blockers(ARB). We should therefore avoid in those with CKD 3-5 and check eGFR 1-2 weeks after starting long-term NSAIDs especially in the elderly and those on ACEI/ARBs.


20% adults and 5% children have a reduction in FEV1 with aspirin and NSAIDs, so avoid use in those with a known sensitivity and be cautious in all asthmatics.

Pregnancy harms

NSAIDs increase the risk of first trimester miscarriage and can cause late pregnancy complications including delayed labour and increased blood loss, so avoid throughout pregnancy but especially the first and third trimesters.

So, what does this mean in practice? Well, unfortunately there’s no such thing as a ‘safe’ NSAID but there may be safer ones and it’s important to weigh up benefits and harms for each individual patient.

The GP Update team run one-day courses, bringing GPs up to date with all the latest evidence and guidelines. For further information about GP Update visit

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