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One trifecta you might not want to pick......combining NSAIDS with ACE-inhibitors and diuretics |
The August 2003 bulletin from the Adverse Drug Reactions Advisory Committee (ADRAC)1 contained a timely warning on the dangers of combining non-steroidal anti-inflammatory drugs (NSAIDs) with ACE-inhibitors and diuretics.
NSAIDs blunt the antihypertensive effects of ACE-inhibitors and Angiotensin-II antagonists (A2RAs), as well as diuretics. This can result in impairment of blood pressure control and a worsening of heart failure symptoms. But there is a more sinister potential for patient harm from this combination. Dr Timothy Mathew outlined these dangers in Current Therapeutics in 2000.2
The afferent blood flow to the glomerulus is aided by vasodilation mediated through prostaglandins. The use of NSAIDs, including COX-2 selective agents can inhibit this vasodilation, resulting in decreased blood supply to the glomerulus.
The efferent blood flow from the glomerulus is controlled by angiontensin-II. Use of an ACE Inhibitor or A2RA can reduce glomerular pressure and filtration.
The net result of this combination is the loss of haemostatic control in the glomerulus, which is obviously heightened in patients taking diuretics. The result in some patients can be acute renal failure.
The incidence of acute renal failure with this combination is not clear, but seems higher in elderly patients with already compromised renal function. The dangers are becoming increasingly apparent, resulting in the recent alert from ADRAC. Situations were problems can arise include:
- a patient is stable on 2 of these drugs and a third is added (usually the NSAID for a short term condition);
- diuretic doses are increased;
- patients suffer from dehydration e.g. due to vomiting or diarrhoea.
ADRAC estimate the use of one or more drugs from these three groups is responsible for over 50% of drug induced renal failure.1 Ten percent of cases involving this ‘triple whammy’ were fatal.1
The combination products containing an ACE-inhibitor or Angiontensin-II receptor antagonist with a diuretic, e.g. Coversyl Plus, Avapro HCT etc, are increasing in popularity as an option for patients with difficult to control blood pressure. Aspirin is widely available without prescription, and it is likely that ibuprofen products will be available in grocery and supermarket outlets in 2004. These two factors must surely increase the risk of an inadvertent ‘triple whammy’.
It is important to advise patients taking diuretics with ACE-Inhibitors or A2RAs to avoid buying aspirin or other NSAIDs from the pharmacy or supermarket. ADRAC advises to avoid the ‘triple whammy’ where possible and that great care should be taken with the use of NSAIDs and ACE-Inhibitors in patients with renal impairment.
References:
1 Australian Adverse Drug Reactions Bulletin, August 2003, 22(4): 14-15
2 Mathew TH, Current Therapeutics 2000, September:7-9
Jonathan Aldous is a pharmacist at Lismore Base Hospital.
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