The triple whammy of (ACE/ARB) + (diuretic) + (NSAID) - a dangerous trio

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The triple whammy of (ACE/ARB) + (diuretic) + (NSAID) is a dangerous trio 

This common combination of medication is considered a dangerous trio and is also known as the triple whammy.1 There are 4 key points:

  1. Avoid this combination if possible.
  2. Be aware of the risk factors for renal failure e.g. older patients with CHF or liver disease or volume depletion from vomiting/diarrhoea or low fluid intake on hot days.
  3. Take care with older i.e. 75 years patients - check renal function yearly at least.
  4. Advise patients not to self-medicate with NSAIDs when prescribing angiotensin converting enzyme receptor/ angiotensin II receptor antagonist (ACE/ARB) and diuretics.2

When volume depletion occurs consider stopping any (prescribed or OTC) NSAIDs and monitor renal function and serum potassium levels.1  

There is also the double whammy i.e. NSAID with either diuretics or ACE/ARB, with the numbers needed to harm for one year 300 versus 158 for triple whammy.3


  1. SaferX (2017) Click here
  2. SaferX Patient Information Guide (2016) Click here
  3. Combined use of nonsteroidal anti-inflammatory drugs with diuretics and/or renin–angiotensin system inhibitors in the community increases the risk of acute kidney injury (2015). Click here

    Gems are chosen by the Goodfellow director Dr. Bruce Arroll to be either practice changing or practice maintaining. The information is educational and not clinical advice.

    This Gem is supported by:
    As published in NZ Doctor 11/04/2018