Anti-Inflammatory Drugs

All NSAIDs May Be Linked to MI Risk, Study Indicates

Selective and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of a first Myocardial Infarction, results of an observational study suggest. Diclofenac and ibuprofen seem to pose about as much risk as the COX-2 inhibitor rofecoxib, the study authors say.

Rofecoxib (Vioxx) was withdrawn from the pharmaceutical market at the end of September 2004 after use of the drug was tied to adverse cardiac effects. Since then, however, questions remain, such as whether all NSAIDs share these harmful effects.

Drs. Julia Hippisley-Cox and Carol Coupland, from the University of Nottingham, UK, conducted a population-based nested case-control study using the QRESEARCH database of information from UK general practices. They report their findings in the June 11th issue of the British Medical Journal.

Their study included 9218 cases of a first MI in people between the ages of 25 and 100 during study period from 2000 to 2004, and 86,349 controls matched by age, calendar time, gender and practice.

The authors identified all prescriptions for NSAIDs for each case and control in the 3 years before their index date (specifically celecoxib, rofecoxib, ibuprofen, diclofenac, naproxen, other selective NSAIDs and other nonselective NSAIDs). Their multivariate analyses adjusted for comorbidities, medications, and other confounders.

"We think that enough concerns exist to warrant a reconsideration of the cardiovascular safety of all NSAIDs," the investigators conclude.

In an associated editorial, Dr. Peter Juni, from University of Berne in Switzerland, and colleagues urge that these data be "interpreted with caution," given that they are observational and other trials have yielded discrepant results.

What is called for now, they contend, are complete meta-analyses, which should "help decision making about issues such as the need for additional trials... to establish the best and safest treatment for patients with musculoskeletal pain."

BMJ 2005;330.

NSAIDs and Musculoskeletal Treatment: What Is the Clinical Evidence?

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for musculoskeletal injuries because the conditions are believed to be inflammatory in nature. However, because inflammation is a necessary component in the healing process, decreasing inflammation may prove counterproductive. Also, many tendon injuries called 'tendinitis' are, in fact, degenerative and not inflammatory conditions. An analysis of the pathophysiology and healing of musculoskeletal injuries questions the use of NSAIDs in many treatment protocols. Because NSAIDs have profound side effects, they should not automatically be the first choice for treating musculoskeletal injuries.

Steven D. Stovitz, MD // NSAIDs and Musculoskeletal Treatment: What Is the Clinical Evidence? // The Physician and SportsMedicine 2003 (Jan); 31 (1)

Use Caution With Pain Relievers

Acetaminophen can cause liver injury through the production of a toxic metabolite. The body eliminates acetaminophen by changing it into substances (metabolites) that the body can easily eliminate in the stool or urine. Under certain circumstances, particularly when more acetaminophen is ingested than is recommended on the label, more of the harmful metabolite is produced than the body can easily eliminate. This harmful metabolite can seriously damage the liver.

The signs of liver disease include abnormally yellow skin and eyes (jaundice), dark urine, light-colored stools, nausea, vomiting, and loss of appetite. The signs can be similar to flu symptoms and may go unnoticed for several days if consumers believe their symptoms are related to their initial illness. Serious cases of liver disease may lead to mental confusion, coma, and death.

Steven D. Stovitz, MD // Use Caution With Pain Relievers // FDA Consumer magazine January-February 2003

Acetaminophen use in children: more is not better

Acetaminophen is the active ingredient in Tylenol and other fever and pain relievers..At least 24 children in the US have died and three have required liver transplants after receiving accidental overdoses of acetaminophen. All the children involved were aged 10 years or younger, and 21 were aged 2 years or younger. Parents may have given acetaminophen longer than is recommended "because fever persisted."

Heubi JE, Bien JP // Acetaminophen use in children: more is not better // J Pediatr 1997 (Feb); 130 (2): 175-177

NSAIDS Associated with Kidney Disease

Nephrotic syndrome due to membranous nephropathy should be recognized as an idiosyncratic drug reaction to many NSAIDS. In addition to diclofenac and fenoprofen, which have previously been implicated, ibuprofen, nabumetone, naproxen, and tolmetin were found to be associated. Because withdrawal of the drug may result in prompt and complete recovery of normal renal function, a history of NSAID intake should be sought in patients with membranous nephropathy.

Radford MG Jr, Holley KE, Grande JP, Larson TS, Wagoner RD, Donadio JV, McCarthy JT //  Reversible membranous nephropathy associated with the use of nonsteroidal anti-inflammatory drugs // JAMA 1996 (Aug 14); 276 (6): 466-469

NSAIDS Side-Effects Epidemic

"There is an epidemic of adverse drug reactions to NSAID's. The Food and Drug Administration believes anywhere from 10,000 to 20,000 deaths each year are the result of severe bleeding caused by NSAID's. It is a big problem."

Dr. James F. Fries. Professor of Medicine at Stanford University School of Medicine // in Marsa L. "America's Other Drug Problem," // Los Angeles Times Magazine, September 29, 1996

Gastro-intestinal Peforation and NSAIDS

Current studies lack appropriate data on aspirin and other risk factors for gastrointestinal perforation. The aim of this study was to obtain the best estimate on aspirin and nonaspirin nonsteroidal anti-inflammatory drug (NSAID) use in these patients. NSAID use is strongly associated with an increased risk of both upper and lower gastrointestinal perforation. The high prevalence of aspirin (over-the-counter) use suggests that future introduction of new NSAIDs may not have a major impact on decreasing gastrointestinal complications if other measures are not taken.

Lanas A, Serrano P, Bajador E, Esteva F, Benito R, Sainz R // Evidence of aspirin use in both upper and lower gastrointestinal perforation // Gastroenterology 1997 (Mar);   112 (3):   683-689

Which is Safer: Cervical Manipulation or Anti-Inflammatory drugs?

A review of the literature to evaluate the risk of serious injury or death resulting from cervical manipulation and to assess the evidence that cervical manipulation is an effective treatment for mechanical neck pain was performed. Another review of the literature to assess the risks and effectiveness of nonsteroidal anti-inflammatory drugs (NSAIDs), which are often used as the "conventional" first-line treatment for similar musculoskeletal conditions

As for comparative safety, the best available evidence indicates that NSAID use poses a significantly greater risk of serious complications and death than the use of cervical manipulation for comparable conditions. In conclusion, the best evidence indicates that cervical manipulation for neck pain is much safer than the use of NSAIDs, by as much as a factor of several hundred times. There is no evidence tha indicates NSAID use is any more effective than cervical manipulation for neck pain.

Dabbs V, Lauretti WJ // A risk assessment of cervical manipulation vs. NSAIDs for the treatment of neck pain // J Manipulative Physiol Ther 1995 (Oct);   18 (8):   530-536