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
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
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
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.