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Do Nonsteroidal Anti-inflammatory Drugs Affect Blood Pressure? A Meta-Analysis

Anthony G. Johnson, MBBS; Tuan V. Nguyen, MApplStat; and Richard O. Day, MD
[+] Article and Author Information

From St. Vincents Hospital and the University of New South Wales, Sydney, Australia. Requests for Reprints: Anthony G. Johnson, MBBS, FRACP, Department of Clinical Pharmacology, Princess Alexandra Hospital, Woolloongabba 4102 Qld Australia. Acknowledgments: The authors thank Dr. Robert Cummings for his comments and the Clinical Trials Coordinator, Suzanne Duffy, for her assistance with the blinding process. Grant Support: Dr. Johnson was a National Health & Medical Research Council of Australia scholar.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1994;121(4):289-300. doi:10.7326/0003-4819-121-4-199408150-00011
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Purpose: A meta-analysis of randomized trials studying the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on blood pressure.

Data Sources and Study Selection: Eight databases were searched, yielding 38 randomized, placebo-controlled trials and 12 randomized but not placebo-controlled trials (comparing two or more NSAIDs).

Data Extraction: Pooled mean treatment effects were computed in each trial for blood pressure, weight, creatinine clearance, plasma renin activity, and daily urinary excretion of sodium and prostaglandins. Meta-analyses of these variables were done for all randomized, controlled trials; for all randomized, uncontrolled trials; and for several subgroups.

Data Synthesis: When pooled, NSAIDs elevated supine mean blood pressure by 5.0 mm Hg (95% CI, 1.2 to 8.7 mm Hg) but had no effect on variables other than blood pressure. Nonsteroidal anti-inflammatory drugs antagonized the antihypertensive effect of β-blockers (blood pressure elevation, 6.2 mm Hg; CI, 1.1 to 11.4 mm Hg) more than did vasodilators and diuretics. Among NSAIDs, piroxicam produced the most marked elevation in blood pressure (6.2 mm Hg; CI, 0.8 to 11.5 mm Hg), whereas sulindac and aspirin had the least hypertensive effect.

Conclusions: Nonsteroidal anti-inflammatory drugs may elevate blood pressure and antagonize the blood pressure-lowering effect of antihypertensive medication to an extent that may potentially increase hypertension-related morbidity. Although certain NSAIDs and antihypertensive agents could be more likely to produce these effects, the underlying mechanisms require further study.

Figures

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Figure 1.
Meta-analysis of randomized, placebo-controlled trials according to population type.

N = total number of volunteers or patients; trials = total number of trials; HTN-Antihyp stat = patients with hypertension administered a single dose of antihypertensive medication; regular = patients with controlled hypertension; HTN-Uncontrolled = patients with uncontrolled hypertension; Normal-Antihyp = normotensive volunteers administered antihypertensive medication; Normal = normotensive volunteers with no history of hypertension. Dots represent mean difference in mm Hg between the effects of the nonsteroidal anti-inflammatory drug and placebo on blood pressure adjusted for baseline. The dashes identify the line of no difference between the effects of the nonsteroidal anti-inflammatory drug and placebo on blood pressure. Error bars show 95% CIs.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Meta-analysis of randomized, placebo-controlled trials according to antihypertensive type.

N = total number of volunteers or patients; trials = total number of trials. Dots represent mean difference in mm Hg between the effects of the nonsteroidal anti-inflammatory drug and placebo on blood pressure adjusted for baseline in patients taking different antihypertensive agents. The dashes identify the line of no difference between the effects of the nonsteroidal anti-inflammatory drug and placebo on blood pressure. Error bars show 95% CIs.

Grahic Jump Location
Grahic Jump Location
Figure 3.
Meta-analysis of randomized, placebo-controlled trials according to nonsteroidal anti-inflammatory drug type.

N = total number of volunteers or patients; trials = total number of trials. Dots represent mean difference in mm Hg between the effects of the nonsteroidal anti-inflammatory drug and placebo on blood pressure adjusted for baseline. The dashes identify the line of no difference between the effects of the nonsteroidal anti-inflammatory drug and placebo on blood pressure. Error bars show 95% CIs.

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