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Abstract

N

NSAIDs inhibit renal prostaglandin synthesis, affect control of hypertension, and are risk factors for congestive heart failure (CHF). COX-2-specific NSAIDs also affect renal function, increase BP, and have been associated with an increase in myocardial infarctions (VIGOR study). is not a specific COX-2 inhibitor, but has little effect on renal prostaglandin secretion and had less of an association with CHF than IB or traditional NSAIDs in a large cohort study (1). Effects on BP (mean of 3 sitting measurements) were studied in a double-blind, randomized, placebo-controlled 1-month study of N 1g bid (n=91), C 200mg bid (n=87), IB 800 mg tid (n=91) and P (n=91) in hypertensive patients (18-75 yrs) stabilized for > 3 months (DBP <95 mm Hg) on ACE inhibitors uid. The study had 90% power to show equivalence of N to P [upper 98% CI for difference in change from baseline < 9mm Hg SBP and < 5 mm Hg DBP] and 94% power to show N and C different from IB (2-sided α of 1.67 to keep overall p < 0.05 for 3 comparisons). Change (mean ± SE) in BP from Baseline (mm Hg): (See Table)

PlaceboCelecoxibNabumetoneIbuprofen
DBP0.1 ± 0.81.0 ± 0.91.0 ± 0.93.3 ± 0.9
SBP-2.1 ± 1.41.3 ± 1.52.2 ± 1.45.3 ± 1.4
PlaceboCelecoxibNabumetoneIbuprofen
DBP0.1 ± 0.81.0 ± 0.91.0 ± 0.93.3 ± 0.9
SBP-2.1 ± 1.41.3 ± 1.52.2 ± 1.45.3 ± 1.4
PlaceboCelecoxibNabumetoneIbuprofen
DBP0.1 ± 0.81.0 ± 0.91.0 ± 0.93.3 ± 0.9
SBP-2.1 ± 1.41.3 ± 1.52.2 ± 1.45.3 ± 1.4
PlaceboCelecoxibNabumetoneIbuprofen
DBP0.1 ± 0.81.0 ± 0.91.0 ± 0.93.3 ± 0.9
SBP-2.1 ± 1.41.3 ± 1.52.2 ± 1.45.3 ± 1.4
N

was equivalent to P with a difference in DBP of 0.9 mm Hg (98% CI -1.9, 3.7) and difference in SBP of 4.2 mm Hg (98% CI -0.2, 8.7). (C also would be equivalent to P.) The increase in BP with N was less than with IB: DBP (p=0.06), 68%; SBP (p=0.10, 59%), and the increase with C was also less than with IB: DBP (p=0.05), 71%; SBP (p=0.03), 75%. Post-hoc analyses showed that SBP increased > 20 mm to > 140 mm in 1 P, 5 N, 4 C, and 15 IB patients (p < 0.02, IB vs P, C or N; P vs C or N = NS). Both non-selective N and COX-2 selective C differ from IB with respect to BP control in hypertensive patients on ACE inhibitors; N was equivalent to P in effect on BP control. 1. Donnan PT. Pharmacoepidem. Drug Safety 2000;8:S115. SmithKline Beecham Pharmaceuticals (Employee)

COX inhibition, Nabumetone, Celecoxib
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© American Journal of Hypertension, Ltd. 2001
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