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.
“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 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.
Data supporting the unintended consequences of such changes in treatment priorities come from a study by Dr. Cronstein, Dr. Paul R. Esserman professor of medicine at New York University, and his associates. They conducted a nested case-control study of 3,830 elderly patients with osteoarthritis (OA) in the Geisinger Health Plan in Danville, Pa., who had 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-selective or nonselective NSAIDs.
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analgesics as the sole prescription medication for pain relief in elderly OA patients more than doubled after Vioxx was withdrawn from the market.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-selective agents.
Dr. Cronstein noted that the AHA 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 – noncardiovascular 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, he 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.
He cited a large Medicare study conducted that examined the comparative safety of analgesics in elderly arthritis patients and concluded that narcotic analgesics come up short.
The investigators, at Brigham and Women's Hospital, Boston, 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-selective NSAID, or a narcotic analgesic during 1999-2005. They came up with 4,280 propensity score–matched patients in each of the three groups.
The composite incidence of fractures of the hip, pelvis, humerus, or radius was 26 per 1,000 person-years in 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 linked with increased risk of falls and fractures, another finding in this study proved unexpected: The composite cardiovascular event rate was 77 per 1,000 person-years with nonselective NSAIDs, 88 per 1,000 with COX-2-selective NSAIDs, and 122 with narcotic analgesics.
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. The GI bleeding risk was 40% lower in the COX-2-selective NSAID group than in the other groups. The all-cause mortality risk was 87% greater in the narcotic analgesic group than with nonselective NSAIDs, while COX-2-selective NSAIDs weren't tied to increased risk (Arch. Intern. Med. 2010;170:1968-78).
This work was funded by the National Institutes of Health, the Geisinger Clinic, and the Clinical and Translational Science Institute. Dr. Cronstein has served as a paid consultant to Allos, Bristol-Myers Squibb, Novartis, and several other pharmaceutical companies.
'You're trading off falls and fractures for MIs,' while hip fracture is significantly deadlier than MI after age 65.
Source DR. CRONSTEIN