Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison

Cannon, Christopher P.; Curtis, Sean; FitzGerald, Garret A.; Krum, Henry; Kaur, Amandeep; Bolognese, James A.; Reicin, Alise; Bombardier, Claire; Weinblatt, Michael E.; Heijde, Desirée van der; Erdmann, Erland; Laine, Loren

doi:10.1016/s0140-6736(06)69666-9

Cited by 462 publications

(345 citation statements)

References 46 publications

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“…64 With Ͼ43 000 patient-years of exposure, adjudicated APTC end points for etoricoxib (60 and 90 mg once daily) and diclofenac (75 mg twice daily) were similar. These results are also important, because some of the patient population was evaluated for 2 years.…”

Section: Evaluating CV Events In Clinical Trials Of Arthritis With Comentioning

confidence: 93%

Cardiovascular Effects of the Cyclooxygenase Inhibitors

White

2007

Hypertension

100

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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 ...

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Section: Evaluating CV Events In Clinical Trials Of Arthritis With Comentioning

confidence: 93%

Cardiovascular Effects of the Cyclooxygenase Inhibitors

White

2007

Hypertension

100

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“…As expected, both selective and non-selective COX inhibitors can impair renal flow and glomerular filtration, as well as sodium and potassium excretion, which leads to swelling, pressure increase and hyperkalemia. This was confirmed by numerous studies [16,18]. Moreover, it was demonstrated that selective COX-2 inhibitors inhibit renin secretion in the macula densa, stimulated by a decrease in sodium concentration.…”

Section: Organ Toxicitymentioning

confidence: 54%

“…Furthermore, it was demonstrated that coxibes nullify the anticoagulant action of small doses of aspirin. On the other hand, reports of an increased risk of myocardial infarction during treatment with coxibes are yet to be confirmed [16]. Animal tests did, however, demonstrate increased sensitivity of cardiac muscle cells to prostacyclin-deficiency-dependent ischaemia.…”

Section: Organ Toxicitymentioning

confidence: 95%

Organ and prenatal toxicity of nonsteroidal anti-inflammatory drugs

Dyndor

Dworzański

Pliszczynska-Steuden

et al. 2015

Current Issues in Pharmacy and Medical Sciences

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Non-selective cyclooxygenase (COX) inhibitors, commonly referred to as nonsteroidal anti-inflammatory drugs (NSAIDs), are among the most taken pharmaceuticals. In adults, they can have a series of side effects, including especially gastroenterotoxicity, hepatotoxicity, nephrotoxicity, chondrotoxicity, and neurotoxicity, and they can induce allergic reactions. Any exacerbation of symptoms depends on the chemical structure of the drug, its dosage and duration of exposure, individual sensitivity, comorbidities and the degree of inhibition of basic COX isoenzymes -the constitutive (COX-2) and induced (COX-1) expressions. However, data on prenatal toxicity are inconsistent. Classic nonselective COX inhibitors do not result in an increase in the risk of developing significant congenital defects; however, if used in the late-pregnancy period, they can have an adverse effect on the foetus, by inducing the premature closure of the ductus arteriosus and by producing a tocolytic effect. Individual reports also indicate the increased risk of developing heart and anterior abdominal wall defects, as well as hypospadias.

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“…В общем итоге, в этих трех проектах, обозначенных как «программа MEDAL», приняли участие 34 701 пациент с ОА и РА (см. таблицу) [27].…”

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“…Та-ким образом, эторикоксиб показал наряду с высокой эф-фективностью хороший профиль безопасности [27]. Еще одной группой препаратов для купирования ХБ являются антидепрессанты, которые оказывают поло-жительный эффект у 50-60% больных с ХБ.…”

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