Medline ® Abstract for Reference 4

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 beta-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.