Safety of Anti-inflammatory Drugs

If you asked most doctors whether they preferred their patients take fewer anti-inflammatory drugs, most would say "yes." If you asked most people with joint pain, they would probably answer the same way--they would like to take less of the drugs. One of the key reasons that doctors support self-care programs is that these efforts not only improve quality of life, but they may also limit the long term use of anti-inflammatory drugs.

This is with good reason. It has been estimated that 5 to 7 percent of hospital admissions are related to adverse drug effects. Some 30 percent of these hospitalizations are due to gastrointestinal, kidney, or allergic effects of aspirin or non-aspirin anti-inflammatory drugs—drugs commonly used to treat joint pain (indomethacin, ibuprofen, naproxen, etc..)

In the United States alone, the cost of treating complications from NSAIDs is more than $2 billion per year. Looked at another way, for every dollar spent on NSAIDs, one more dollar is spent treating NSAID-induced complications. When it comes to adverse effects, some NSAIDs are more problematic than others. The table below lists some commonly used NSAIDs and the relative risk (RR) they pose to GI bleeding. No treatment is given a relative risk of 1.0. [http://www.ncchc.org/pubs/CC/nsaids.html]

Table 1. Relative Risk
NSAID	RR
None	1.0
Ibuprofen	2.1
Diclofenac	2.7
Ketoprofen	3.2
Naproxen	4.3
Indomethacin	5.5
Piroxicam	9.3
Ketorolac	24.7

Who Should be Cautious of NSAIDs?

According to the American College of Rheumatology, the following people should be especially cautious about taking NSAIDs. Those who:

have decreased kidney or liver function, or an uncontrolled or undiagnosed liver problem (e.g., hepatitis)
have had a recent ulcer, gastritis, or bleeding from the intestinal tract or if you have had these problems in the past
take blood thinners like Coumadin, heparin, aspirin, or Plavix
take steroids like prednisone
have a low platelet count
have Crohn's disease or ulcerative colitis
have a history of stroke, heart attack, hypertension, or congestive heart failure
have asthma or chronic lung disease
are allergic to aspirin or other NSAIDs, or have nasal polyps
have "reflux disease", indigestion or hiatal hernia
are pregnant, may become pregnant, or breast feeding
drink more than seven alcoholic drinks per week or more than two in a day
are over the age of 65

http://www.rheumatology.org/public/factsheets_original/nsaids.asp

Doctors in Norway have recently analysed 23 human clinical trials to estimate the pain relieving effects of non-steroidal anti-inflammatory drugs (like aspirin, ibuprofen, indomethacin, and others) in patients who had osteoarthritis of the knee. The final sample included 7,767 people receiving NSAIDs and 3,078 who received a placebo.

The analysis revealed that NSAIDs can reduce short term pain slightly better than placebo, but it does not support long term use of NSAIDs for this condition. The advantage of anti-inflammatory drugs over placebo for short term pain relief is "small and probably clinically insignificant" according to the study authors.

The doctors directing this study concluded that "As use of oral NSAIDs may incur serious adverse effects, they can only be recommended for limited use in osteoarthritis of the knee." [emphasis added]

[Pirmohamed, M, James, S, Meakin, S, et al. Adverse drug reactions as cause of admission to hospital: Prospective analysis of 18,820 patients. BMJ. 2004;329:15-9.]

In using these anti-inflammatory drugs, it is important to understand that they principally address pain and inflammation. They do not alter the disease process of osteoarthritis. This statement is not meant to minimize the impact of pain on your daily quality of life. Pain is a significant influence and should be considered as such.

However, many doctors now believe that the side effects of these drugs should be carefully considered in light of their limited impact on the disease process itself.

[Simon, LS. The COX 2 selective inhibitors: What the newspapers have not told you. Bulletin of the NYU Hospital for Joint Diseases 2007;65(3):229-41.]

Dr. T. Pinkus and colleagues conducted two recent controlled studies comparing NSAIDs (such as diclofenac or celecoxib, etc.) to analgesics (such as acetaminophen or Tylenol). The people were asked which of the therapies they preferred. The studies were designed as “crossover” studies, so the patients tried one treatment, then switched to the other. This way they were able to compare how they felt on both.

People generally got more pain relief from NSAIDs, but they also had more gastrointestinal distress. Ironically, people in both studies said they preferred NSAIDs over acetaminophen, even though the gastrointestinal side effects were greater.

[Pincus T, Koch GG, Sokka T, et al. A randomized, double-blind, crossover clinical trial of diclofenac plus misoprostol versus acetaminophen in patients with osteoarthritis of the
hip or knee. Arthritis Rheum 2001;44:1587-98.]

[Pincus T, Koch G, Lei H, et al. Patient preference for placebo, acetaminophen or celecoxib efficacy studies (PACES): Two randomized placebo-controlled cross-over clinical trials in patients with osteoarthritis of the knee or hip. Ann Rheum Dis 2004;63:931-9.]

Risk of Adverse Cardiovascular Events

Although the AHA statement suggested that the COX-2 selective inhibitors should be the court of final therapeutic resort, there seem to be little data supporting that contention from the presented evidence, particularly when considering the chronic doses typically used in arthritis. As previously stated, there appears to be an increased risk for CV events with all of the available NSAIDs. Furthermore, Pincus and colleagues demonstrated that the use of an antiinflammatory drug is both more efficacious and preferable to the patients than the use of an analgesic alone in the treatment of patients with OA.8,9