Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study

Graham, David J.; Campen, David; Hui, Rita L.; Spence, Michele M.; Cheetham, Craig; Levy, Gerald; Shoor, Stanford; Ray, Wayne A.

doi:10.1016/s0140-6736(05)17864-7

Cited by 728 publications

(295 citation statements)

References 30 publications

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“…Using a Cox proportional hazards analysis for hazard ratios of death and rehospitalization for MI, they reported a significant increased risk with use of any nonselective NSAID and the selective COX-2 inhibitors. As was observed in the study by Graham et al, 68 the risk of cardiac events appeared to be increased with higher doses of the NSAIDs. A substantial number of observational studies were examined and pooled by McGettigan and Henry 70 for Ͼ1 000 000 patients from cohort and case-control studies.…”

Section: White CV Effects Of Cox Inhibitors 413supporting

confidence: 71%

“…68 Using a casecontrol design, Graham et al 68 studied Ϸ1.4 million people, who were observed for 2 years. Nonusers (including those who were remote users) of NSAIDs served as control subjects, and nonfatal MI and sudden cardiac death associated with the use of various NSAIDs and COX-2 selective agents were then compared.…”

Section: Observational Studies That Have Assessed the CV Risk Of Nsaimentioning

confidence: 99%

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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: White CV Effects Of Cox Inhibitors 413supporting

confidence: 71%

Section: Observational Studies That Have Assessed the CV Risk Of Nsaimentioning

confidence: 99%

Cardiovascular Effects of the Cyclooxygenase Inhibitors

White

2007

Hypertension

100

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“…During various pathologic events, COX-2 is highly upregulated; therefore, COX-2 inhibitors have been considered to be potential therapeutic remedies against stroke. Unfortunately, clinical trials associate COX-2 inhibitors with enhanced risk of cardiovascular complications (Bresalier et al 2005;Graham et al 2005). Therefore, focus has shifted toward the cascade of prostaglandins downstream of COX enzymes.…”

mentioning

confidence: 99%

Prostaglandin D2 DP1 receptor is beneficial in ischemic stroke and in acute exicitotoxicity in young and old mice

Ahmad

Maruyama

et al. 2010

AGE

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The cardiovascular complications reported to be associated with cyclooxygenase inhibitor use have shifted our focus toward prostaglandins and their respective receptors. Prostaglandin D 2 and its DP1 receptor have been implicated in various normal and pathologic conditions, but their role in stroke is still poorly defined. Here, we tested whether DP1 deletion aggravates N-methyl-D-aspartic acid (NMDA)-induced acute toxicity and whether DP1 pharmacologic activation protects mice from acute excitotoxicity and transient cerebral ischemia. Moreover, since the elderly are more vulnerable to stroke-related damage than are younger patients, we tested the susceptibility of aged DP1 knockout (DP1 −/− ) mice to brain damage. We found that intrastriatal injection of 15 nmol NMDA caused significantly larger lesion volumes (27.2±6.4%) in young adult DP1 −/− mice than in their wild-type counterparts. Additionally, intracerebroventricular pretreatment of wild-type mice with 10, 25, and 50 nmol of the DP1-selective agonist BW245C significantly attenuated the NMDA-induced lesion size by 19.5± 5.0%, 39.6±7.7%, and 28.9±7.0%, respectively. The lowest tested dose of BW245C also was able to reduce middle cerebral artery occlusion-induced brain infarction size significantly (21.0±5.7%). Interestingly, the aggravated NMDA-induced brain damage was persistent in older DP1 −/− mice as well. We conclude that the DP1 receptor plays an important role in attenuating brain damage and that selective targeting of this receptor could be considered as an adjunct therapeutic tool to minimize stroke damage.

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“…These effects have been shown to be more severe in several animal species rather than in human beings (Khan and McLean, 2012). Selective COX-2 inhibitors were designed to prevent those adverse effects mediated by inhibition of COX-1 (Zhang et al, 1997;Hinz and Brune, 2002), but prolonged use of COX-2-selective inhibitors may, as with NSAIDs, confer a risk of cardiovascular events, including hypertension, edema, heart attack and stroke (Graham et al, 2005;Lenzer, 2005;Solomon et al, 2005). The cause of the adverse cardiovascular effects remains unclear, but it may include an imbalance in prostacyclin and thromboxane levels in the endothelium (Bing and Lomnicka, 2002) and blockade of prostanoid actions on renal function (Nasrallah and Hebert, 2005).…”

Section: Introductionmentioning

confidence: 99%

CJ-023,423 (Grapiprant) a Potential Novel Active Compound with Antihyperalgetic Properties for Veterinary Patients

Giorgi¹

2015

American Journal of Animal and Veterinary Sciences

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Companion animals are now living longer and so are more commonly manifesting age-and pain-related disease. Nonsteroidal antiinflammatory drugs are the most used drug in osteoarthritis and inflammatory pain of various aetiologies. Despite their safety profiles have been amended from the COX-non selective to the COX-2 selective inhibitor class, some adverse effects are still of concern especially in long term treatments. One prostaglandin (PG) downstream from the cyclooxygenase enzyme, PGE2, has been recognized as a pivotal mediator of pain and inflammation. The actions of PGE2 are produced by its interaction with four G-protein coupled receptors (EP1, EP2, EP3 and EP4). The EP4 receptor mediates PGE2-elicited sensitization of sensory neurons and studies have demonstrated that EP4 is a major receptor in mediating pain associated with both rheumatoid and osteoarthritis and in inflammation. CJ-023,423 (grapiprant) is a competitive antagonist of human and rat prostanoid EP4 receptors, under development for the control of pain and inflammation associated with osteoarthritisfor use in humans and dogs. A recent study has shown the good safety profile of this active ingredient in dogs. Despite this molecule is still far to be marketed because it pharmacokinetic/pharmacodynamics profile is need to be fully elucidated yet, it might be an interesting active ingredient for the veterinary medicine.

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Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study

Cited by 728 publications

References 30 publications

Cardiovascular Effects of the Cyclooxygenase Inhibitors

Cardiovascular Effects of the Cyclooxygenase Inhibitors

Prostaglandin D2 DP1 receptor is beneficial in ischemic stroke and in acute exicitotoxicity in young and old mice

CJ-023,423 (Grapiprant) a Potential Novel Active Compound with Antihyperalgetic Properties for Veterinary Patients

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