Effects of Celecoxib on Ambulatory Blood Pressure in Hypertensive Patients on ACE Inhibitors

White, William Β.; Kent, Jeffrey D.; Taylor, Addison A.; Verburg, Kenneth M.; Lefkowith, James B.; Whelton, Andrew

doi:10.1161/01.hyp.0000014323.99765.16

Cited by 141 publications

(83 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In one of our earlier placebo-controlled trials, ambulatory BP monitoring was used to assess the effect of high-dose celecoxib (200 mg BID) in 178 patients who were on chronic ACE inhibitor therapy. 54 This study demonstrated that celecoxib (400 mg total daily dose) was associated with a nonsignificant increase in 24-hour mean BP of 1.6/1.2 mm Hg. Evaluation of the BP curves did suggest a transient (1-to 2-hour) increase in systolic BP after dosing of celecoxib, which could be associated with peak inhibition of COX-2.…”

Section: Effects Of Nsaids and Cox-2 Inhibitors In Treated Hypertensimentioning

confidence: 59%

Cardiovascular Effects of the Cyclooxygenase Inhibitors

White

2007

Hypertension

Self Cite

106

View full text Add to dashboard Cite

C yclooxyenase (COX)-2 selective inhibitors were developed to create a new class of nonsteroidal antiinflammatory drugs (NSAIDs) with properties similar to those of nonselective NSAIDS but without their potential COX-1-mediated gastrointestinal toxicities. 1,2 Studies of the various COX-2 selective inhibitors have shown that they are in fact associated with a significantly lower risk of upper and lower gastrointestinal complications than traditional NSAIDs, except in patients who are taking concomitant low-doses of aspirin.Recent evidence also suggests that some doses of the COX-2 selective inhibitors, and perhaps some traditional NSAIDs as well, are associated with an increased risk of adverse cardiovascular (CV) events. Reports of a higher incidence of myocardial infarction (MI) among patients with arthritis taking high doses of the COX-2 selective inhibitor rofecoxib compared with those taking the NSAID naproxen 2-4 have had heightened concerns since 2001 regarding selective COX-2 inhibitor safety. In addition, in early 2005, elevated CV event rates were reported in patients with spontaneous adenomatous polyps who were taking high doses of celecoxib compared with placebo 5 and in patients who received parenteral parecoxib followed by oral valdecoxib versus placebo immediately after coronary artery bypass graft surgery. 6 This article represents a compilation of the data concerning the effects of both nonselective and selective NSAIDs on blood pressure (BP), particularly in patients with hypertension and/or on antihypertensive agents. Subsequently, the impact that the COX inhibitors have on CV events from several recent clinical trials for the treatment of arthritis or for cancer prevention, as well as from selected large observational studies, is discussed. CV Pharmacology of COX InhibitionCOXs participate in numerous physiological functions and human pathological disorders. The COX-1 isoform is constitutively expressed in most tissues where it regulates the synthesis of prostaglandins. COX-1 is the only form of the enzyme in mature platelets and is also expressed in the vascular endothelium, the gastrointestinal epithelium, brain, spinal cord, and kidney. The COX-2 isoform plays an important role in induction of inflammation in response to injury, as well as later repair of inflammation. It is noteworthy that COX-2 may be induced by bacterial endotoxins, cytokines, and growth factors and is expressed in atherosclerotic plaques, during angiogenesis, during wound healing, and in a variety of epithelial cell cancers. [7][8][9] In addition, COX-2 is constitutively expressed in the macula densa and renal medullary interstitium. 10,11 As discussed below, one result of COX-2 inhibition is a reduction in natriuresis and the development of hypertension in susceptible populations. The COX isoenzymes are similar in structure, but the substrate-binding channel of COX-2 contains a side pocket that is absent in COX-1. This structural difference has allowed for the design and development of COX inhibitors with side chains ...

show abstract

Section: Effects Of Nsaids and Cox-2 Inhibitors In Treated Hypertensimentioning

confidence: 59%

Cardiovascular Effects of the Cyclooxygenase Inhibitors

White

2007

Hypertension

Self Cite

106

View full text Add to dashboard Cite

show abstract

“…Rofecoxib caused the greatest increase in systolic BP in patients who received ACE inhibitors or ␤ blockers, whereas those who were on calcium channel antagonists or diuretic monotherapy and received either celecoxib or rofecoxib showed no significant increases in BP. However, in a randomized, double-blind, placebo-controlled, parallel-group clinical trial that involved 178 patients with essential hypertension and that used 24-h ambulatory recordings and high doses (400 mg/d, twice the recommended dose) of celecoxib, there was no evidence of any significant alteration of the antihypertensive effect of the ACE inhibitor lisinopril during a 4-wk period (58). Interpretation of these studies is complicated by uncertainty about comparisons of equivalence of potency and duration of action of the two coxibs (rofecoxib and celecoxib).…”

Section: Effect Of Cox-2 Inhibitors On Salt and Water Homeostasis And Bpmentioning

confidence: 99%

Update on Cyclooxygenase-2 Inhibitors

Harris

Breyer

2006

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Nonsteroidal anti-inflammatory drugs represent the most commonly used medications for the treatment of pain and inflammation, but numerous well-described side effects can limit their use. Cyclooxygenase-2 (COX-2) inhibitors were initially touted as a therapeutic strategy to avoid not only the gastrointestinal but also the renal and cardiovascular side effects of nonspecific nonsteroidal anti-inflammatory drugs. However, in the kidney, COX-2 is constitutively expressed and is highly regulated in response to alterations in intravascular volume. COX-2 metabolites have been implicated in mediation of renin release, regulation of sodium excretion, and maintenance of renal blood flow. This review summarizes the current state of knowledge about both renal and cardiovascular side effects that are attributed to COX-2 selective inhibitors.Clin J Am Soc Nephrol 1: 236 -245, 2006236 -245, . doi: 10.2215 N onsteroidal anti-inflammatory drugs (NSAID) are the most commonly used class of medications for the treatment of pain and inflammation and represent one of the most common classes of medications used worldwide, with an estimated usage of Ͼ30 million per day (1). Nonselective NSAID inhibit both constitutive cyclooxygenase-1 (COX-1) and inducible cyclooxygenase-2 (COX-2), the rate-limiting enzymes that are involved in production of prostaglandins and thromboxane. In addition to their role in inflammation, prostaglandins are important regulators of vascular tone, salt and water balance, and renin release, and nonselective NSAID exhibit adverse effects, including salt retention and reduced GFR, which may elevate BP or make pre-existing hypertension worse (2). It has been estimated that as many as 2.5 million Americans experience NSAID-mediated renal effects yearly (3). Risk factors that predispose to NSAID-induced renal functional alterations include age Ͼ65 yr, cardiovascular disease, diabetes, male gender, high NSAID dosage, and concurrent use of other nephrotoxic drugs (3). Up to 20% of patients who take nonselective NSAID and have more than one of these risk factors may manifest alterations in renal function.In addition to renal side effects, nonselective NSAID have long been known to predispose to gastrointestinal (GI) toxicity. It has been estimated that one third of patients who taking long-term nonselective NSAID develop endoscopically proven gastric or duodenal ulcers (4). The risk for serious bleeding from these lesions is somewhat lower, with approximately 100,000 hospitalizations for GI complications of NSAID (5). One study estimated that nonselective NSAID-induced GI abnormalities constitute the 15th leading cause of death in the United States (6). The premise that COX-1 performs cellular "housekeeping" functions for normal physiologic activity and is the predominant isoform expressed in platelets and the GI tract, whereas COX-2 acts at inflammatory sites, led to the development of COX-2 selective inhibitors. It also was originally hypothesized that the renal effects of nonselective NSAID were also linked to COX-...

show abstract

“…35,36 Similar effects have been described with the selective cyclooxygenase-2 (COX-2) inhibitors. 37,38 Although NSAIDs have an overall modest effect on blood pressure levels, in susceptible individuals significant fluid retention, increases in blood pressure, and/or acute kidney disease may occur. These effects presumably occur secondary to inhibition of renal prostaglandin production, especially prostaglandin E 2 and prostaglandin I 2 , with subsequent sodium and fluid retention.…”

Section: Drug-related Causesmentioning

confidence: 99%

Resistant Hypertension: Diagnosis, Evaluation, and Treatment

Calhoun¹,

Jones²,

Textor³

et al. 2008

Circulation

1,261

401

View full text Add to dashboard Cite

Abstract-Resistant hypertension is a common clinical problem faced by both primary care clinicians and specialists. While the exact prevalence of resistant hypertension is unknown, clinical trials suggest that it is not rare, involving perhaps 20% to 30% of study participants. As older age and obesity are 2 of the strongest risk factors for uncontrolled hypertension, the incidence of resistant hypertension will likely increase as the population becomes more elderly and heavier. The prognosis of resistant hypertension is unknown, but cardiovascular risk is undoubtedly increased as patients often have a history of long-standing, severe hypertension complicated by multiple other cardiovascular risk factors such as obesity, sleep apnea, diabetes, and chronic kidney disease. The diagnosis of resistant hypertension requires use of good blood pressure technique to confirm persistently elevated blood pressure levels. Pseudoresistance, including lack of blood pressure control secondary to poor medication adherence or white coat hypertension, must be excluded. Resistant hypertension is almost always multifactorial in etiology. Successful treatment requires identification and reversal of lifestyle factors contributing to treatment resistance; diagnosis and appropriate treatment of secondary causes of hypertension; and use of effective multidrug regimens. As a subgroup, patients with resistant hypertension have not been widely studied. Observational assessments have allowed for identification of demographic and lifestyle characteristics associated with resistant hypertension, and the role of secondary causes of hypertension in promoting treatment resistance is well documented; however, identification of broader mechanisms of treatment resistance is lacking. In particular, attempts to elucidate potential genetic causes of resistant hypertension have been limited. Recommendations for the pharmacological treatment of resistant hypertension remain largely empiric due to the lack of systematic assessments of 3 or 4 drug combinations. Studies of resistant hypertension are limited by the high cardiovascular risk of patients within this subgroup, which generally precludes safe withdrawal of medications; the presence of multiple disease processes (eg, sleep apnea, diabetes, chronic kidney disease, atherosclerotic disease) and their associated medical therapies, which confound interpretation of study results; and the difficulty in enrolling large numbers of study participants. Expanding our understanding of the causes of resistant hypertension and thereby potentially allowing for more effective prevention and/or treatment will be essential to improve the long-term clinical management of this disorder. (Circulation. 2008;117:e510-e526.)

show abstract

Effects of Celecoxib on Ambulatory Blood Pressure in Hypertensive Patients on ACE Inhibitors

Cited by 141 publications

References 22 publications

Cardiovascular Effects of the Cyclooxygenase Inhibitors

Cardiovascular Effects of the Cyclooxygenase Inhibitors

Update on Cyclooxygenase-2 Inhibitors

Resistant Hypertension: Diagnosis, Evaluation, and Treatment

Contact Info

Product

Resources

About