Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Review: Nonsteroidal anti-inflammatory drugs may elevate blood pressure

ACP J Club. 1995 Jan-Feb;122:4. doi:10.7326/ACPJC-1995-122-1-004


Source Citation

Johnson AG, Nguyen TV, Day RO. Do nonsteroidal anti-inflammatory drugs affect blood pressure? A meta-analysis. Ann Intern Med. 1994 Aug 15;121:289-300.


Abstract

Objective

To determine the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on blood pressure (BP) using meta-analysis.

Data sources

Studies were identified using MEDLINE (1966 to 1990), EMBASE/Excerpta Medica (1974 to 1990), Biosis (1969 to 1990), Diogenes (1976 to 1990), Science Citation Index (1972 to 1990), International Pharmaceutical Abstracts (1970 to 1990), IOWA Drug Information Service (1966 to 1990), and the Combined Health Information Database (1973 to 1990). Keywords included in each search were meta-analysis, research design, double-blind method, double-blind study, double, blind, random allocation, random, control, clinical trials, anti-inflammatory agents, nonsteroidal, hypertension, blood pressure, and the names of individual NSAIDs. Additional studies were identified by reviewing the bibliographies of relevant papers and textbooks.

Study selection

Randomized controlled trials of the effects of NSAIDs on BP as a primary outcome were selected. A measure of BP variability also had to be reported.

Data extraction

Data pertaining to patient characteristics, key study design features, treatment administered, and BP change were extracted. Pooled mean treatment effects were computed in each trial for BP, weight, creatinine clearance, plasma renin activity, and daily urinary excretion of sodium and prostaglandins. Meta-analyses of these variables were computed for all randomized placebo-controlled trials, for all randomized trials without placebo controls, and for various subgroups.

Main results

50 randomized placebo-controlled and 16 randomized non-placebo-controlled trials (comparing ≥ 2 NSAIDs) met the selection criteria. In most of the studies, treatment duration was less than 3 months. When data were pooled for the randomized placebo-controlled trials, NSAIDs elevated supine mean BP by 5.0 mm Hg (95% CI 1.2 to 8.7 mm Hg) but had no effect on body weight, daily urinary sodium output, creatinine clearance, or urinary prostaglandin excretion per 24 hours. Subgroup analyses also showed no statistically significant effects of NSAIDs on the non-BP variables. No statistically significant difference existed in BP elevation according to antihypertensive drug class or according to individual NSAID; however, the trend was toward greater effect with β-blockers and vasodilators than with diuretics, and the trend was toward more elevation with piroxicam, indomethacin, and ibuprofen than with aspirin.

Conclusions

Nonsteroidal anti-inflammatory drugs elevate blood pressure and antagonize the blood pressure-lowering effect of some antihypertensive agents. Small sample sizes precluded definitive conclusions about the effect of individual nonsteroidal anti-inflammatory drugs on individual antihypertensive drug classes.

Source of funding: National Health and Medical Research Council of Australia.

For article reprint: Dr. A.G. Johnson, Medicines Research Unit, James Lance Glaxo Wellcome, Randwick New South Wales 2031, Australia. FAX 61-2-9382-4053.


Commentary

The meta-analysis by Johnson and colleagues confirms that NSAIDs elevate mean supine BP in hypertensive patients aged 26 to 56 years. Piroxicam, indomethacin, and ibuprofen tend to produce the most marked elevation in BP, and aspirin tends to produce the least elevation in BP. The analysis also suggests that NSAIDs antagonize the BP-lowering effect of β-blockers and that NSAIDs possibly antagonize the effect of vasodilators more than they antagonize the effect of diuretics. None of these subgroup comparisons, however, was statistically significant.

In another recent study of patients aged 65 years and older, Gurwitz and colleagues (1) found an increased risk for initiation of antihypertensive therapy in patients placed on NSAIDs. The odds ratio for initiation of antihypertensive therapy increased with increased doses of the NSAID. Indomethacin at all doses had a high odds ratio.

For the clinician following patients on NSAIDs who develop poorly controlled hypertension, several strategies should be considered. First, the patient should be titrated down to the smallest effective dose of the NSAID. Although definitive comparative studies of the risk for hypertensive effects for each of the NSAIDs do not exist, the data suggest that indomethacin and piroxicam appear to have a greater risk for elevating BP. Therefore, in the appropriate patient, a change of NSAIDs may be helpful. Finally, in those patients who are to remain on NSAIDs and who have poorly controlled hypertension, using diuretics rather than β-blockers or vasodilators may be recommended with careful follow-up of renal function.

Abraham Sunshine, MD
New York University Medical CenterNew York, New York, USA


Reference

1. Gurwitz JH, Avorn J, Bohn RL, et al. Initiation of antihypertensive treatment during nonsteroidal anti-inflammatory drug therapy. JAMA. 1994;272:781-6.