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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n\u003Cp id=\u0022p-1\u0022\u003EThirty million people worldwide take non-steroidal anti-inflammatory drugs (NSAIDS) for the treatment of chronic pain and inflammation. In light of the cardiovascular (and renal) risks associated with NSAIDS, this article discusses whether clinicians safely use these drugs in their practices.\u003C\/p\u003E\n\u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EInflammatory Disease\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EThirty million people worldwide take non-steroidal anti-inflammatory drugs (NSAIDS) for the treatment of chronic pain and inflammation. In light of the cardiovascular (and renal) risks associated with NSAIDS, can clinicians safely use these drugs in their practices?\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThe spectrum of biological effects with NSAIDS depends on the selectivity of cyclooxygenase (COX) inhibition. COX-1 inhibitors pose gastrointestinal (GI) toxicity but may have antithrombotic effects. COX-2 inhibitors may have less GI toxicity but can have prothrombotic potential, which seems to differ across individual drugs within the coxib class (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). Cardiovascular risk may be dose-related and possibly duration-related, said Debabrata Mukherjee, MD, of the Gill Heart Institute, University of Kentucky, Lexington.\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/7\/1\/14\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Implications of Relative Degrees of Selectivity.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-852714080\u0022 data-figure-caption=\u0022Implications of Relative Degrees of Selectivity.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/7\/1\/14\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/7\/1\/14\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/7\/1\/14\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/10954\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \u003Cp id=\u0022p-4\u0022 class=\u0022first-child\u0022\u003EImplications of Relative Degrees of Selectivity.\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-5\u0022\u003EJames Brophy, MD, of Westmount, Canada, who explored the post-marketing data on NSAIDS, described an important meta-analysis published last year (\u003Cem\u003EBr Med J.\u003C\/em\u003E 2006;332:1302\u20138) in which the relative risk for cardiovascular events for all COX-2 inhibitors was increased by 42% compared with placebo. Individual differences were difficult to show. \u201cThere are 121 randomized controlled trials,\u201d he remarked, \u201cbut we still have outstanding questions.\u201d\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EObservational studies help to fill this gap. The largest studies all show increased cardiovascular risks with rofecoxib (Vioxx\u00ae) (14% to 80%), but results are inconsistent for celecoxib (Celebrex\u00ae), particularly in standard doses. Patients without previous myocardial infarction (MI) have a 23% increased risk with rofecoxib but no increased risk with celecoxib; in patients with previous MI, however, risk is increased by 59% with rofecoxib and by 40% with celecoxib.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EDr. Mukherjee agreed. \u201cThe totality of the data suggests that celecoxib is not worse than the older NSAIDS though there is a signal of risk at higher doses,\u201d he said. \u201cThe black box warning is for \u003Cem\u003Eall\u003C\/em\u003E the coxibs. If you need an NSAID, naproxen may be the least toxic.\u201d\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EUnresolved questions might be answered by the Prospective Randomized Evaluation of Celecoxib Integrated Safety Versus Ibuprofen or Naproxen (PRECISION) trial, which will assess the relative cardiovascular safety of three of the most commonly used pain relievers. The study will enroll patients with arthritis and either coronary heart disease or multiple risk factors for heart disease, and follow them for the occurrence of cardiovascular events.\u003C\/p\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n\u003Ch2 class=\u0022\u0022\u003EManaging the Cardiac Patients Who Needs NSAIDS\u003C\/h2\u003E\n\u003Cp id=\u0022p-9\u0022\u003EElliott Antman, MD, of the Brigham and Women\u0027s Hospital, Boston, said that in his practice he uses NSAIDS only as necessary and in patients at the lowest cardiovascular risk, in the lowest possible doses, using the lowest risk agents and the shortest duration of treatment. In patients deemed to have no risk for substance abuse, short-term narcotics may actually be a better choice, he added.\u003C\/p\u003E\n\u003Cp id=\u0022p-10\u0022\u003EIn a study reported at the American Heart Association 2006, Gibson, et al showed that among patients suffering an ST-segment-elevation MI, the adjusted risk for death or MI was increased by 29% in patients who were taking NSAIDS within the prior week. Dr. Antman advised clinicians to be sure their MI patients were not continued on NSAIDS when admitted.\u003C\/p\u003E\n\u003Cp id=\u0022p-11\u0022\u003EHe commented, \u201cCOX-2-selective NSAIDS should not be the first line but the last line of treatment today,\u201d advising clinicians to closely monitor patients should they prescribe NSAIDS (\u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E).\u003C\/p\u003E\n\u003Cdiv id=\u0022F2\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/7\/1\/14\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Pharmacologic Therapy for Musculoskeletal Symptoms in Patients with Known CVD or Risk Factors for IHD.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-852714080\u0022 data-figure-caption=\u0022Pharmacologic Therapy for Musculoskeletal Symptoms in Patients with Known CVD or Risk Factors for IHD.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/7\/1\/14\/F2.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/7\/1\/14\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/7\/1\/14\/F2.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/10957\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 2.\u003C\/span\u003E \u003Cp id=\u0022p-12\u0022 class=\u0022first-child\u0022\u003EPharmacologic Therapy for Musculoskeletal Symptoms in Patients with Known CVD or Risk Factors for IHD.\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n\u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n\u003Ch2 class=\u0022\u0022\u003ENSAIDS and the Kidney: What is the Danger?\u003C\/h2\u003E\n\u003Cp id=\u0022p-13\u0022\u003EMichael E. Farkouh, MD, Mt. Sinai Heart Clinical Trials Unit, New York, emphasized that dose-dependent renal effects also occur in up to 5% of patients following long-term use of NSAIDS. In light of the coxib controversy, concerns over renal toxicity are increasing, he said.\u003C\/p\u003E\n\u003Cp id=\u0022p-14\u0022\u003EProblems include acute renal failure, hypertension, congestive heart failure, fluid and electrolyte abnormalities, nephritic syndrome, and papillary necrosis. Patients most at risk include those with age-related decline in glomerular filtration rate, hypovolemia, loop diuretic use, heart failure, cirrhosis and nephrosis.\u003C\/p\u003E\n\u003Cp id=\u0022p-15\u0022\u003ERisk for acute renal failure with NSAIDS varies by the preparation, according to a recent epidemiologic study (\u003Cem\u003EAm J Epidemiol\u003C\/em\u003E. 2006;164:881\u20139). Naproxen and rofecoxib carry the highest adjusted relative risk over non-exposure (about 2.3 fold); celecoxib\u0027s risk is 1.5 and meloxicam\u0027s risk is nearly 1.3. Multiple studies have demonstrated that adverse renal effects with rofecoxib are dose-related.\u003C\/p\u003E\n\u003Cp id=\u0022p-16\u0022\u003EAnother significant problem is the aggravation of hypertension with NSAIDS. When patients require treatment with both antihypertensive agents and NSAIDS, Dr. Farkouh advised, \u201cDon\u0027t disregard the blood pressure effects of these drugs and make sure your office measures blood pressure reliably.\u201d He recommended using lower doses of the NSAID (nonselective or coxib), titrating the antihypertensive, reducing salt intake, questioning patients about over-the-counter NSAID use, and considering aspirin or a non-opioid analgesic instead.\u003C\/p\u003E\n\u003Cp id=\u0022p-17\u0022\u003EIn contrast to current agents, a new agent, lumiracoxib (Prexige\u00ae), has a greatly improved renal safety profile and, especially at low doses, is associated with less heart failure compared with other agents, Dr. Farkouh said.\u003C\/p\u003E\n\u003Cdiv id=\u0022F3\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/7\/1\/14\/F3.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-852714080\u0022 data-figure-caption=\u0022\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure3\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/7\/1\/14\/F3.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/7\/1\/14\/F3.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure3\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/7\/1\/14\/F3.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/10960\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\n\u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2007 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/7\/1\/14.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzmbe2\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzmbe2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}