Comparison of rofecoxib, celecoxib, and naproxen on renal function in elderly subjects receiving a normal‐salt diet

Schwartz, Jules I.; Vandormael, K.; Malice, Marie Pierre; Kalyani, Rubana N.; Lasseter, Kenneth C.; Holmes, Gregory B.; Gertz, Barry J.; Gottesdiener, Keith; Laurenzi, Martino; Redfern, K.-J.; Brune, Kay

doi:10.1067/mcp.2002.126182

Cited by 124 publications

(69 citation statements)

References 38 publications

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“…Because rofecoxib and other NSAIDs can cause small mean increases in blood pressure (Gertz et al, 2002;Schwartz et al, 2002), and there is some evidence to suggest that increased blood pressure might be associated with an increased risk of dementia (Skoog, 1997;Birkenhager et al, 2001), we also performed two post hoc analyses to evaluate whether the rofecoxib : placebo risk ratio for diagnosis of AD increased as a function of increased blood pressure change. In the first analysis, change from baseline in mean arterial blood pressure (defined as (2 Â diastolic blood pressure þ systolic blood pressure)/3) at month 4 was calculated for each patient.…”

Section: Resultsmentioning

confidence: 99%

“…It could be speculated that the apparent increased conversion to AD might be secondary to a non-AD-specific aspect of rofecoxib's biological effects. For example, rofecoxib and other NSAIDs can cause small mean increases in blood pressure (Gertz et al, 2002;Schwartz et al, 2002). It has been suggested that increased blood pressure might be associated with an increased risk of dementia, although the evidence is inconsistent (Skoog, 1997;Birkenhager et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

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A Randomized, Double-Blind, Study of Rofecoxib in Patients with Mild Cognitive Impairment

Thal

Ferris

Kirby

et al. 2005

Neuropsychopharmacol

372

219

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Inflammatory mechanisms have been implicated in Alzheimer's disease (AD) and might be mediated via the COX-2 enzyme. Previous studies with the selective COX-2 inhibitors, rofecoxib and celecoxib, have shown that they do not alter the progression of AD. We conducted a double-blind study to investigate whether rofecoxib could delay a diagnosis of AD in patients with mild cognitive impairment (MCI), a group with an expected annual AD diagnosis rate of 10-15%. MCI patients X65 years were randomized to rofecoxib 25 mg (N ¼ 725) or placebo (N ¼ 732) daily for up to 4 years. The primary end point was the percentage of patients with a clinical diagnosis of AD. The estimated annual AD diagnosis rate was lower than the anticipated 10-15%: 6.4% in the rofecoxib group vs 4.5% in the placebo group (rofecoxib : placebo hazard ratio ¼ 1.46 (95% CI: 1.09, 1.94), p ¼ 0.011). Analyses of secondary end points, including measures of cognition (eg the cognitive subscale of the AD Assessment Scale (ADAS-Cog)) and global function (eg the Clinical Dementia Rating (CDR)), did not demonstrate differences between treatment groups. There was also no consistent evidence that rofecoxib differed from placebo in post hoc analyses comparing ADAS-Cog and CDR-sum of boxes scores in overlapping subgroups of patients who had Mini Mental State Exam scores of 24-26 in the present MCI study and in a previous AD treatment study with a similar design. The results from this MCI study did not support the hypothesis that rofecoxib would delay a diagnosis of AD. In conjunction with the lack of effects observed in previous AD studies, the findings suggest that inhibition of COX-2 is not a useful therapeutic approach in AD.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A Randomized, Double-Blind, Study of Rofecoxib in Patients with Mild Cognitive Impairment

Thal

Ferris

Kirby

et al. 2005

Neuropsychopharmacol

372

219

View full text Add to dashboard Cite

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“…33 COX-2 inhibitors have also been shown to cause sodium retention in a small percentage of human subjects without renal impairment, 24,46,47 and decreased urinary sodium excretion for the first 72 hours of administration of COX-2 inhibitors is seen in subjects with salt depletion 36 or in elderly subjects on a normal-salt diet. 35,38,48 When renal cortical blood flow (CBF) and medullary blood flow (MBF) were selectively measured in mice, it was found that acute infusion of a COX-1 selective inhibitor did not affect either cortical blood flow or medullary blood flow. In contrast, a COX-2 selective inhibitor significantly reduced medullary blood flow without altering cortical blood flow.…”

Section: Renal Medullary Cox-2mentioning

confidence: 99%

Cyclooxygenases, the Kidney, and Hypertension

2004

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Abstract-Selective cyclooxygenase (COX)-2 inhibitors that are in widespread clinical use were developed to avoid side effects of conventional NSAIDs, including gastrointestinal and renal toxicity. However, COX-2 is constitutively expressed in the kidney and is highly regulated in response to alterations in intravascular volume. COX-2 metabolites have been implicated in maintenance of renal blood flow, mediation of renin release, and regulation of sodium excretion. COX-2 inhibition may transiently decrease urine sodium excretion in some subjects and induce mild to moderate elevation of blood pressure. Furthermore, in conditions of relative intravascular volume depletion and/or renal hypoperfusion, interference with COX-2 activity can have deleterious effects on maintenance of renal blood flow and glomerular filtration rate. In addition to physiological regulation of COX-2 expression in the kidney, increased renal cortical COX-2 expression is seen in experimental models associated with altered renal hemodynamics and progressive renal injury (decreased renal mass, poorly controlled diabetes), and long-term treatment with selective COX-2 inhibitors ameliorates functional and structural renal damage in these conditions. Key Words: COX-2 Ⅲ COX-1 Ⅲ hypertension Ⅲ renin Ⅲ sodium Ⅲ glomerular filtration rate Ⅲ kidney I n the kidney, prostaglandins are important mediators of vascular tone, salt and water balance, and renin release. The rate-limiting enzyme, cyclooxygenase (prostaglandin synthase G 2 /H 2 ) initiates the metabolism of arachidonic acid to prostaglandin (PG) G 2 and subsequently to PGH 2 , which is then further metabolized by tissue-specific isomerases to PGs and thromboxane. There are at least two distinct cyclooxygenases, COX-1 and COX-2, that share Ϸ60% homology 1 but are the products of different genes and have distinct patterns of expression and regulation. COX-1 has been termed "constitutive," because of its wide tissue distribution, while COX-2 has been designated as "inducible" because of its more restricted basal expression and its upregulation by inflammatory and/or proliferative stimuli and its central role in mediation of inflammatory conditions and malignancies. Recently, Chandrasekharan et al characterized a third potential cyclooxygenase isoform, COX-3, a 65-kDa membranebound protein with acetaminophen or paracetamol-sensitive cyclooxygenase activity that represents a splice variant of COX-1. 2 However, other investigators have not confirmed the existence of full-length, catalytically active COX-3 from human genomic clones. Therefore, it remains uncertain whether COX-3 in fact represents the elusive target of paracetamol.Inhibition of COX activity by NSAIDs has been widely used for the treatment of pain and inflammation. Because prostanoids are involved in renal function, nonselective NSAIDs exhibit adverse effects, including salt retention and decreases in glomerular filtration rate (GFR), which may elevate blood pressure (BP) or make pre-existing hypertension worse. 3 Based on the hypothesis...

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“…Nonselective COX inhibitors, which inhibit both isoforms, have been reported to prevent tumorigenesis (Peura, 2002;Schwartz et al, 2002). However, the use of nonselective COX inhibitors is often associated with gastrointerestinal (GI) adverse events, whereas COX-2 selective inhibitors are thought to exert antiinflammatory and their antineoplastic properties with diminished toxicity (Hirata et al, 1997;Wolfe, 1998;Wolfe et al, 1999;Lichtenstein and Wolfe, 2000).…”

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confidence: 99%

Cyclooxygenase-2 selective inhibition with NS-398 suppresses proliferation and invasiveness and delays liver metastasis in colorectal cancer

et al. 2004

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Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to reduce the risk and mortality of colorectal cancer (CRC) by inhibiting the activity of cyclooxygenase (COX). The present studies were directed to determine whether selective COX-2 inhibition reduces CRC tumour cell proliferation and invasion/migration, and the possible cellular and molecular mechanisms involved. The MC-26 cells are a highly invasive mouse CRC cell line expressing COX-2 protein. NS-398 (100 mM), a highly selective COX-2 inhibitor, decreased cell proliferation by B35% of control, as determined using [ 3 H]-thymidine incorporation. This reduction in cell proliferation was associated with decreased expression of cyclin D1 and proliferating cell nuclear antigen (PCNA). Furthermore, NS-398 inhibited cell invasion/migration through Matrigel extracellular matrix components at 24 h by B60%. The addition of exogenous prostaglandin E 2 partially attenuated the inhibition of cell invasion by 10 mM NS-398, but failed to reverse the effect of 100 mM NS-398. Matrix metalloproteinases-2 (MMP-2) and -9 (MMP-9) are two enzymes that facilitate cell invasion/migration by degrading the extracellular matrix. In the presence of 100 mM NS-398, Western blot hybridisation analysis and zymography demonstrated that both MMP-2 and MMP-9 protein levels and enzyme activity were decreased by B25 -30%. In separate studies, NS-398 also inhibited tumour growth in vivo and retarded the formation of liver metastasis. The results of these studies indicate that the expression and activity of COX-2 appear to be associated with both the proliferative and invasive properties of CRC. Cyclooxygenase-2 inhibition suppresses tumour cell growth and invasion/migration, and retards liver metastasis in a mouse colon cancer model, via multiple cellular and molecular mechanisms.

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Comparison of rofecoxib, celecoxib, and naproxen on renal function in elderly subjects receiving a normal‐salt diet

Cited by 124 publications

References 38 publications

A Randomized, Double-Blind, Study of Rofecoxib in Patients with Mild Cognitive Impairment

A Randomized, Double-Blind, Study of Rofecoxib in Patients with Mild Cognitive Impairment

Cyclooxygenases, the Kidney, and Hypertension

Cyclooxygenase-2 selective inhibition with NS-398 suppresses proliferation and invasiveness and delays liver metastasis in colorectal cancer

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