Effects of celecoxib on ambulatory blood pressure in hypertensive patients on ACE inhibitors.
Nonselective nonsteroidal anti-inflammatory agents have been shown to attenuate the antihypertensive efficacy of ACE inhibitors with average increases in systolic blood pressure (BP) of 5 to 10 mm Hg. Less is known about the specific cyclooxygenase-2 (COX-2) inhibitors now widely used for the treatment of arthritis. The objective of this study was to determine the effects of celecoxib compared with placebo on 24-hour BP levels in ACE inhibitor-treated patients with hypertension. This was a randomized, double-blind, placebo-controlled, parallel-group clinical trial involving 178 men and women (mean age, 53 years) with essential hypertension who were treated and controlled with lisinopril monotherapy (10 to 40 mg daily). Baseline BP values were obtained using 24-hour ambulatory recordings. Patients received either celecoxib, 200 mg twice daily (twice the recommended dose for osteoarthritis) (n=91), or placebo (n=87) for 4 weeks, and changes in the 24-hour BP, body weight, and clinical laboratory parameters were assessed. Mean changes from baseline in the 24-hour systolic and diastolic BP were 2.6/1.5+/-0.9/0.6 mm Hg on celecoxib versus 1.0/0.3+/-1/0.6 mm Hg on placebo (P=0.34 for systolic BP; P=0.45 for diastolic BP). The proportion of patients whose 24-hour BP increased by at least 5, 10, 15, or 20 mm Hg were also similar on celecoxib and placebo. No changes in body weight, serum creatinine, or potassium occurred in either group. Thus, these data demonstrate that high doses of celecoxib have no significant effect on the antihypertensive effect of the ACE inhibitor lisinopril. The placebo-subtracted changes observed in 24-hour BP (1.6/1.2 mm Hg) are less than what has been reported for nonselective nonsteroidal anti-inflammatory agents in ACE inhibitor-treated patients.
White
William B
WB
Section of Hypertension and Clinical Pharmacology, University of Connecticut School of Medicine, Farmington, CT 06030-3940, USA. wwhite@nso1.uchc.edu
Kent
Jeffrey
J
Taylor
Addison
A
Verburg
Kenneth M
KM
Lefkowith
James B
JB
Whelton
Andrew
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D018660:Blood Pressure Monitoring, Ambulatory; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007700:Kinetics; D017706:Lisinopril / Q000627:therapeutic use*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D013449:Sulfonamides / Q000009:adverse effects / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D017706:Lisinopril; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib