Effect of rofecoxib, celecoxib, and naproxen on blood pressure (BP) in elderly volunteers

Nonsteroidal anti-inflammatory drugs (NSAIDs) can affect sodium reabsorption by decreasing the synthesis of renal prostaglandins. This and other effects may lead to increased BP. Since Cox-2 is constitutively expressed in the kidney, it is hypothesized that the effects of COX-2 inhibitors would be similar to nonselective NSAIDs. This study evaluated the effects of 2 COX-2 inhibitors (rofecoxib, 25 mg QD and celecoxib, 200 mg BID), a nonselective NSAID (naproxen, 500 mg BID), and placebo on BP during a 2-week in-house administration. 67 healthy elderly (60 to 80 years) subjects participated in a double-blind, placebo-controlled, parallel-group study. The subjects were not hypertensive nor on antihypertensive therapy. Subjects received a weight-maintaining isocaloric diet (200 mEq sodium, ~0.8 g/kg protein, 80 to 120 mEq potassium daily), beginning 8-13 days prior to the first dose of study drug. After attaining sodium balance [based on stable weight (within 0.5 kg) and 24-hour urinary sodium between 180 to 220 mEq on 2 consecutive days], subjects were randomized to treatment. Daily BP measurements were taken at 8AM and 8PM, and more often (8AM, Noon, 4PM, and 8PM) on Days-1, 1, 7, and 14. Least-Squares mean changes from baseline (±SE) for average daily BP on Day 14 (prespecified primary endpoint for BP) are presented below: (See Table) There was no significant difference between treatment groups for any parameter. No incidence of peripheral edema occurred during the 2 week treatment. Two subjects experienced elevated systolic BP during the course of the trial (one on each COX-2 inhibitor). These results obtained under well-controlled conditions for two weeks, suggest that COX-2 selective agents have effects on BP that are not different from non-selective NSAIDS. Grant/Research Support - Merck Research Laboratories Other Financial or Material Support - Employee of Merck