NSAIDs, analgesics and nondrug approaches

1
Musculoskeletal pain

• NSAIDs, analgesics and non-drug approaches

2
Houston, we have a problem(1)MeReC Extra. Issue
30. November 2007

• All NSAIDs carry a risk of GI side-effects
• Risk increases with age, presence of
  co-morbidities and dose of NSAID
• Coxibs have a lower GI risk than traditional
  NSAIDS
• Dyspepsia can still occur and may be as common as
  with traditional NSAIDs
• Severe and sometimes fatal GI reactions can occur
• Not all coxibs may be equal
• Benefits diminished when co-administered with
  aspirin
• Low dose ibuprofen has a lower GI risk than
  diclofenac and naproxen
• Using a PPI significantly reduces the risk of
  serious GI adverse effects and dyspepsia with any
  NSAID
• No good evidence that adding a PPI to a coxib is
  more beneficial than adding a PPI to a
  traditional NSAID

3
Houston, we have a problem(2)MeReC Extra. Issue
30. November 2007

• Coxibs cause a small increased absolute risk of
  thrombotic events compared with placebo
• The excess risk is estimated to be about 3 cases
  per 1000 users treated for one year on average
• This risk increases with dose and persists
  throughout treatment
• All coxibs are contraindicated for patients with
  established ischaemic heart disease, peripheral
  arterial disease and/or cerebrovascular disease
• Diclofenac 150mg has a thrombotic risk profile
  similar to that of the coxibs
• Ibuprofen 1200mg/d and naproxen 1000mg/d have a
  lower risk
• Cardio-renal effects are not affected by COX-2
  selectivity, and contribute to CV risk

4
CV risks? - Its a volume thingMeReC Extra.
Issue 30. November 2007

• Prescribing of coxibs may be responsible for
  approximately 240 additional or premature CV
  events per year in England alone
• Approximately 2000 additional or premature CV
  events per year could be caused by diclofenac
  prescribing

NSAID prescribing in England April to June 2007
total items (4.3 million)
5
But what about the GI effects?Lewis SC, et al.
Br J Clin Pharmacol 2002 54 320-6Langman MJ,
et al. Lancet 1994 343 1075-8
Naproxen
Diclofenac
Ibuprofen
Paracetamol
6
What do we need to consider?

• For the individual patient there will be a
  trade-off along each of these dimensions

Cardiovascular risks
Symptoms and response to treatment
Gastrointestinal risks
7
So, whats the deal?

• For patients taking NSAIDs which carry a higher
  CV risk
• Switching to paracetamol 4g/day
• Will reduce cardiovascular risk
• Will reduce gastrointestinal risk
• Efficacy?
• Switching to ibuprofen 1200mg/day
• Will reduce cardiovascular risk
• Will reduce gastrointestinal risk (especially if
  use a PPI as well)
• Efficacy?
• Switching to naproxen 1g/day
• Will reduce cardiovascular risk
• May increase gastrointestinal risk (but what
  about using a PPI?)
• Efficacy?

8
Who should we prioritise for review?

• People at high CV risk
• Those with established CVD
• Those taking CV medication, especially aspirin
  and clopidogrel
• Older men
• Smokers
• People with diabetes

• People at high GI risk
• Age gt65 years
• History of GI bleeding, ulcer or perforation
• Those taking medicines that increase risk of
  upper-GI AEs (e.g. warfarin, aspirin and
  corticosteroids)
• Serious comorbidity, e.g. CV disease, renal or
  hepatic impairment, diabetes, or hypertension
• Prolonged duration or maximum doses of NSAID
• Excessive alcohol use
• Heavy smoking

• Some risk factors increase both CV and GI risk
  people with these need particular attention

9
3 steps to NSAID HeavenTM

• Dont use them unless you have to
• The only way to avoid NSAID side-effects is not
  to use them
• Paracetamol works for many
• Employ non-drug interventions routinely
• Consider short-term course (1-2 weeks) of topical
  NSAID
• Consider glucosamine and chondroitin
• If you have to use them, use them wisely
• The balance of benefits and risks needs to be
  carefully assessed think about CV, GI and renal
  issues routinely
• Use a safer drug (ibuprofen, then naproxen) in
  the lowest effective dose for the shortest period
  
• NSAID users should be a high priority for
  medication review Are NSAIDs effective/needed?
  Drug holidays? Dont issue repeat prescriptions
  without review.
• Consider gastroprotection in those at high risk
  (NICE definition)
• Options are PPIs, double-dose H2RAs, misoprostol
• Coxibs should be considered only in those at high
  GI risk, but consider also the cardiovascular
  risks
• All of this particularly applies to those aged
  over 65