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Tai-Juan Aw, MBBS, FRACP; Steven Joseph Haas, BPharm, BPharmSci(Hons), MSHPA; Danny Liew, MBBS(Hons), FRACP; Henry Krum, MBBS, PhD, FRACP

Arch Intern Med. 2005;165:(doi:10.1001/archinte.165.5.IOI50013).

Background  Nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed and are associated with blood pressure (BP) elevation. The development of selective cyclooxygenase-2 inhibitors (coxibs) raises the issue of the magnitude of BP response compared with nonselective NSAIDs. We therefore performed a meta-analysis comparing the effects of coxibs with placebo, nonselective NSAIDs, and each other on BP elevation and hypertension.

Methods  Nineteen randomized controlled trials involving coxibs were published before May 2004, with a total of 45 451 participants in which BP data were available. The Cohen method statistically combined weighted mean difference (WMD). The Der Simonian and Laird method pooled results concerning the relative risk (RR) of developing hypertension and the RR of clinically important BP elevations.

Results  Among the trials analyzed, coxibs caused a WMD point estimate increase in systolic and diastolic BP compared with placebo (3.85/1.06 mm Hg) and nonselective NSAIDs (2.83/1.34 mm Hg). Cyclooxygenase-2 inhibitors were associated with a nonsignificantly higher RR of causing hypertension compared with placebo (RR, 1.61; 95% confidence interval [CI], 0.91-2.84; P = .10) and nonselective NSAIDs (RR, 1.25; 95% CI, 0.87-1.78; P = .23). Rofecoxib induced a WMD point estimate increase in systolic BP (2.83 mm Hg) and a nonsignificantly higher risk of developing clinically important systolic BP elevation (RR, 1.50; 95% CI, 1.00-2.26; P = .05) compared with celecoxib.

Conclusions  Cyclooxygenase-2 inhibitors were associated with a point-estimate BP elevation compared with placebo and nonselective NSAIDs. There was a nonsignificantly higher incidence of developing hypertension compared with nonselective NSAIDs, as was observed with rofecoxib compared with celecoxib. These BP elevations may be clinically significant in relation to increased cardiovascular risk.

Published online February 14, 2005 (doi:10.1001/archinte.165.5.IOI50013).

Author Affiliations: Department of Clinical Pharmacology (Drs Aw, Liew, and Krum) and National Health and Medical Research Council (NHMRC) of Australia Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine and Department of Medicine (Mr Haas, Drs Liew and Krum), Monash University, Alfred Hospital, Melbourne, Australia.

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