COX-2 inhibitors associated with blood pressure elevation


CHICAGO – An analysis of 19 randomized controlled trials involving COX-2 inhibitors (selective cyclooxygenase-2 inhibitors) suggests that these agents raise blood pressure more than either conventional nonsteroidal anti-inflammatory drugs (NSAIDs) or placebo, according to a study to be published in an upcoming issue of The Archives of Internal Medicine, one of the JAMA/Archives journals. The study is posted online today because of its relevance to current events surrounding this class of drugs. It will be published in a future print edition of the journal.

NSAIDs, among the most widely prescribed drugs for pain relief, are associated with gastrointestinal side effects. As a result there has been a significant preference to prescribe COX-2 inhibitors over conventional NSAIDs, even when patients do not meet specified criteria for treatment, according to background information in the article. Some COX-2 inhibitors have been associated with an increased risk of cardiovascular events.

Tai-Juan Aw, M.B.B.S., F.R.A.C.P., Monash University, Melbourne, Australia, and colleagues, analyzed data from all 19 randomized controlled trials of COX-2 inhibitors published before May 2004, with a total of 45,451 participants for whom blood pressure data were available. The meta-analysis was designed to compare the relative risk of developing hypertension and of clinically important blood pressure elevation in study participants treated with COX-2 inhibitors versus those treated with NSAIDs or placebo.

COX-2 inhibitors were associated with a blood pressure elevation compared with NSAIDs and placebos, the authors found. These blood pressure elevations may be clinically significant in relation to increased cardiovascular risk. The authors also saw differences between the COX-2 inhibitors. "Rofecoxib appears to confer a greater risk of developing hypertension and clinically important elevations in both systolic and diastolic blood pressure compared with celecoxib," they stated.

While COX-2 inhibitors have been considered to be a welcome therapeutic option for arthritis, the authors concluded, "…their potential (and differential) effect on blood pressure elevation requires caution in their use and warrants further investigation. Clinicians need to weigh the risks of improved gastrointestinal safety versus potential hazards of developing elevated blood pressure when considering the use of these agents, especially in the elderly population."

(Arch Intern Med. 2005; 165. Available post-embargo at

Editor's Note: Dr. Liew has been a consultant to Pfizer regarding cyclooxygenase 2 inhibitors, and Prof. Krum has been a consultant to Pfizer, Merck, and Novartis regarding cyclooxygenase 2 inhibitors. Mr. Haas currently receives assistance via a National Health and Medical Research Council Public Health Postgraduate Research Scholarship. Dr. Liew currently receives assistance via a Royal Australasian College of Physicians Postdoctoral Fellowship.

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