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Can an NSAID Trump the Effect of an ACE Inhibitor?

Can an NSAID Trump the Effect of an ACE Inhibitor?

I have read that the concurrent use of an NSAID and an angiotensin-converting enzyme (ACE) inhibitor may impair the antihypertensive effect of the ACE inhibitor. What is the mechanism of this interaction?
—Angela Byerley Haw, ARNP
  Olympia, Wash

Although there is little evidence to implicate NSAIDs as direct antagonists of ACE inhibitors, they may reduce some of the cardiovascular benefits of the latter agents. NSAIDs may have a negative effect on hypertension control through 2 separate mechanisms:

  • NSAIDs may cause sodium retention, which can raise blood pressure, particularly in certain patients-such as those with renal problems.
  • These anti-inflammatory agents inhibit the action of renal prostaglandins. Renal prostaglandins promote vasodilation; by inhibiting this effect, NSAIDs can worsen hypertension.

Concurrent use of NSAIDs and ACE inhibitors can be especially problematic in patients with underlying renal artery stenosis. Prostaglandin inhibition renders the renal arteries less able to dilate, thereby reducing vascular flow in a setting in which renal blood supply is already compromised. This effect is doserelated and is most commonly seen in long-term users of NSAIDs. Judicious and intermittent monitoring of renal function is recommended for patients with renal artery stenosis who are receiving long-term NSAID therapy.

If blood pressure increases in a patient with previously well-controlled hypertension who takes an NSAID and an ACE inhibitor, suspect an underlying kidney disorder.

Because aspirin also has a very strong inhibitory effect on prostaglandins, it seems likely that similar interactions might occur with concomitant use of this agent and ACE inhibitors. A retrospective study of more than 14,000 patients hospitalized for myocardial infarction found no evidence of an adverse interaction between aspirin and ACE inhibitors in this population.1 However, a recent review pointed out that much of the current data concerning this potential interaction are derived from retrospective analyses of studies that were not designed to address this issue.2 Until there is a clear answer to the question of a possible interaction, it may be prudent to limit the aspirin dosage to 100 mg/d in patients with congestive heart failure who are also taking ACE inhibitors.
Robert Bloomfield, MD, MS
  Catherine Miller, PA-C
  Bowman Gray School of Medicine
  Winston-Salem, NC


1. Krumholz HM, Chen Y, Wang Y, Radford MJ. Aspirin and angiotensin-converting enzyme inhibitors among elderly survivors of hospitalization for an acute myocardial infarction. Arch Intern Med. 2001;161:538-544.
2. Peterson JG, Lauer MS. Using aspirin and ACE inhibitors in combination: why the hullabaloo? Cleve Clin J Med. 2001;69:569-574.

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