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Less NSAID for arthritis equals more falls.

SNOWMASS, COLO. - The guideline-endorsed demotion of nonsteroidal anti-inflammatory drugs in favor of narcotic analgesics for chronic pain has led to a marked increase in falls, fractures, and other bad outcomes among elderly arthritis patients.

"I think the real take-home message here is that current guidelines for the treatment of pain should be revisited," Dr. Bruce N. Cronstein asserted at the conference.

Since the cyclo-oxygenase-2 (COX-2)-selective NSAID rofecoxib (Vioxx) was famously taken off the market in late 2004 because of a scandal related to cover-up of an increased risk of myocardial infarction, prescriptions for narcotic analgesics in elderly patients with arthritis have risen sharply. This trend accelerated following the 2007 publication of an American Heart Association scientific statement on the treatment of chronic pain in patients with or at increased risk for heart disease (Circulation 2007;115:1634-42). The AHA guidelines elevated short-term use of narcotic analgesics to first-tier status alongside aspirin, acetaminophen, and tramadol, while demoting both COX-2-selective and nonselective NSAIDs to second-tier status.

The AHA recommendations have been embraced by geriatrics groups and other medical societies. Notably however, the American College of Rheumatology has declined to get on board, observed Dr. Cronstein, Dr. Paul R. Esserman professor of medicine at New York University

The AHA guidelines, in his view, are poorly done. The problem is one of tunnel vision. The guidelines focus on the evidence of increased cardiovascular risk associated with nearly all NSAIDs without considering how the drugs stack up in terms of overall safety - noncardiovascu-lar as well as cardiovascular - compared with the other major analgesic group: narcotic analgesics. And it turns out that the NSAIDs look pretty good in comparison, the rheumatologist added.

"You're trading off falls and fractures for Mis - and it turns out that in patients over age 65, the mortality from hip fracture is significantly greater than it is for MI," said Dr. Cronstein, who is also director of the Clinical and Translational Science Institute, which is a partnership between New York University and the New York City Health and Hospitals Corporation.

He cited a large Medicare study conducted by investigators at Brigham and Women's Hospital, Boston. They examined the comparative safety of analgesics in elderly arthritis patients and concluded that narcotic analgesics come up short.

The investigators sifted through the population of Medicare beneficiaries in Pennsylvania and New Jersey to identify elderly patients with rheumatoid arthritis or osteoarthritis (OA) who were started on a nonselective NSAID, a COX-2-se-lective NSAID, or a narcotic analgesic during 1999-2005.

The composite incidence of fractures of the hip, pelvis, humerus, or radius in this National Institutes of Health-funded study was 26 per 1,000 person-years among patients on nonselective NSAIDs, 19 with COX-2-selective NSAIDs, and 101 with opioids.

While it's not really surprising that opiate analgesics should be associated with increased risk of falls and fractures, another finding in this study proved unexpected: Intriguingly, the composite cardiozvascular event rate was 77 per 1,000 person-years with nonselective NSAIDs, 88 per 1,000 with COX-2-selective NSAIDs, and 122 in the narcotic analgesics group.

The patients taking opioids had a 77% greater risk of cardiovascular events and those taking COX-2-selective NSAIDs had a 28% greater risk than did patients on nonselective NSAIDs, according to findings from a multivariate Cox regression analysis. The fracture risk was 4.47-fold greater with narcotic analgesics than with NSAIDs (Arch. Intern. Med. 2010; 170: 1968-78).

Dr. Cronstein also presented highlights of a not-yet-published study that documented the changing pattern of analgesic prescriptions for elderly patients with OA since 2005. He conducted the study with coinvestigators at the Geisinger Health Plan in Danville, Pa.

During 2001-2004, 24% of elderly patients with OA in the Geisinger system were on a narcotic-only for pain relief, 15% were on a narcotic analgesic plus a COX-2-selective NSAID, and 13% were on COX-2-selective NSAID monotherapy But 2005-2009, 56% of patients were on monotherapy with a narcotic analgesic, 9% were on a narcotic plus a-selective NSAID, and 2% were on COX-2-selective NSAID monotherapy.

Thus, the use of narcotic analgesics as the sole prescription medication for pain relief in elderly OA patients more than doubled after Vioxx was withdrawn from the market. The patients on narcotic analgesics with or without a COX-2-selective NSAID had a fourfold greater rate of falls or fractures than those on nonselective NSAIDs or COX-2-selec-tive agents.

Dr. Cronstein and his coworkers also conducted a nested case-control study of 3,830 elderly Geisinger OA patients with fractures and 11,490 others matched for age and Charlson Comorbidity Index without fractures. In a multivariate analysis, patients on narcotic analgesics had a threefold greater risk of falls or fractures than those on either COX-2-se-lective or nonselective NSAIDs.

This work was funded by the National Institutes of Health, the Geisinger Clinic, and the Clinical and Transla-tional Science Institute. Dr. Cronstein reported that he has served as a paid consultant to Alios, Bristol-Myers Squibb, CanFite Biopharmaceuticals, Cypress Laboratories, Gismo Therapeutics, No-vartis, Protalex, Regeneron, and Savient. He has received research grants from the National Institutes of Health and numerous pharmaceutical companies.

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Title Annotation:RHEUMATOLOGY
Author:Jancin, Bruce
Publication:Internal Medicine News
Date:Mar 1, 2012
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