Can an NSAID Trump the Effect of an ACE Inhibitor?

June 2, 2006

I have read that the concurrent use of an NSAID and an angiotensin-convertingenzyme (ACE) inhibitor may impair the antihypertensive effect of the ACEinhibitor. What is the mechanism of this interaction?

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

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

  • NSAIDs may cause sodium retention, which can raise bloodpressure, 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, NSAIDscan worsen hypertension.

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

If blood pressure increases in a patient with previously well-controlledhypertension who takes an NSAID and an ACE inhibitor, suspect an underlyingkidney disorder.

Because aspirin also has a very strong inhibitory effect on prostaglandins,it seems likely that similar interactions might occur with concomitant use of thisagent and ACE inhibitors. A retrospective study of more than 14,000 patientshospitalized for myocardial infarction found no evidence of an adverse interactionbetween aspirin and ACE inhibitors in this population.1 However, a recentreview pointed out that much of the current data concerning this potential interactionare derived from retrospective analyses of studies that were not designedto address this issue.2 Until there is a clear answer to the question of a possibleinteraction, it may be prudent to limit the aspirin dosage to 100 mg/d in patientswith 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

References:

REFERENCES:1. Krumholz HM, Chen Y, Wang Y, Radford MJ. Aspirin and angiotensin-converting enzyme inhibitors amongelderly 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.