DSI Newsletter: NSAIDs

DSI Newsletters, Issue 50:
NSAIDs

NSAIDs or Non-Steroidal Anti-Inflammatory Drugs are a group of drugs commonly used to treat arthritis because of their analgesic (pain-killing), anti-inflammatory, and antipyretic (fever-reducing) properties.
The mechanism of action of NSAIDs is the inhibition of the enzyme Cyclooxygenase (or COX, for short), which catalyzes arachidonic acid to prostaglandins and leukotrienes. Arachidonic acid is released from membrane phospholipids as a response to inflammatory stimuli. Prostaglandins establish the inflammatory response.
There are two forms (isoforms) of COX: COX-1 and COX-2. COX-1 helps maintain good health; ie: provide mucus coat to the stomach lining. When COX-1 is blocked, side effects like stomach ulcers occur. COX-2 is formed in response to an injury or inflammation. When COX-2 is blocked, pain is diminished.
There are many NSAIDs available. High dose Aspirin (two 325 mgm pills 4x daily) acts like an NSAID by blocking one COX-1 for every COX-2. The first generation NSAIDs block two COX-2s for every COX-1 and include: Ibuprofen, Motrin, Advil, Aleve, Naprosyn, Anaprox, Voltaren, Arthrotec, Dolobid, Lodine, Ansaid, Indocin, Orudis, Toradol, Relafen, Daypro, Feldene, Clinoril, Tolectin, Mobic, and others. The second generation (COX-2 inhibitors) block many (about 100) COX-2s for every COX-1, and are theoretically safer for the stomach and include: Celebrex, Vioxx, and Bextra.
There has been negative public opinion recently about NSAIDs in general that begun with Merck withdrawing Vioxx from the market over concerns that there were more Cardiac and Cerebral events than placebo. The APPROVe trial of Vioxx showed 20 per thousand more events than placebo. This was not a trial designed to look at safety, however. It was to prove that Vioxx prevented colon cancer. That is, they didn’t stratify its subjects to heart attach or stroke risk. Merck thought since there was a suspicion that it might be implicated in higher risk; they voluntarily pulled it from the market. An earlier trial, VIGOR, alluded to some Vioxx problems also. Subsequently similar concerns have arisen with Celebrex and naproxen.
This is not surprising since all the NSAIDs have the same basic mechanism of action; that is, blocking COX-2 to alleviate pain.
With the current negative media attention to NSAIDs, along with lawyers advertising to sue everyone, it can be disconcerting for a patient who is in pain and is contemplating taking an NSAID.
The Vioxx literature implies that there might be as high as 2% chance that it causes stroke or heart attack. It is still possible that it does not do this. There are going to be many more lawsuits than 2%, unfortunately. I think that everyone should try to minimize their exposure to NSAIDs while the dust is settling. People that should avoid them should include:

Patients at risk for heart attack or stroke (events).
Patients overly concerned about these events.
Patients who have relatives or close friends that are lawyers.
Anybody who is exposed to the negative media hype of NSAIDs.

Patients that are in pain and can understand the relative risks, benefits and alternative procedures well enough that they would not dream of calling an attorney should they get an event on an NSAID will be well served by them. But keep in mind the following risks taken from Pfizer’s product insert of Celebrex:

Cardiovascular Risk: Celebrex may cause an increased risk of serious cardiovascular thrombotic (blood clot) events, myocardial infarction (heart attack), and CVA (stroke), which can be fatal. All NSAIDs (including Ibuprofen, Advil, Aleve, Motrin, Vioxx, and Bextra) may have a similar risk. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk.
Celebrex is contraindicated for the treatment of perioperative pain in the setting of CABG (Coronary Artery Bypass Graft) Surgery.
GI (Gastrointestinal) Risk: NSAIDs, including Celebrex, cause increased risk of serious gastrointestinal adverse events including: bleeding; ulceration; and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events.
Serious Skin Reactions such as exfoliative dermatitis, Stevens Johnson Syndrome (SJS), and TEN (Toxic Epidermal Necrolysis) have been reported in patients receiving Celebrex. These reactions can be fatal. These events can occur without warning and in patients without prior known sulfa allergy. Celebrex should be discontinued at the first appearance of skin rash, mucosal lesions, or any sign of hypersensitivity.
Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.

Click here for the FDA Statement on the Halting of a Clinical Trial of the Cox-2 Inhibitor Celebrex

Click here for the American Pain Society’s table of Examples of Nonopioid Analgesics

Sincerely:

Joseph Saponaro, MD, DABIM, FACP, CPI, CCI, CCTI, CCRC, CCRP
Board Certified Internist, JPMC
Principal Investigator, DSI
Diplomat American Board of Internal Medicine
Fellow American College of Physicians
Certified Physician Investigator by the AAPP
Certified Clinical Investigator by the DIA
Certified Clinical Research Investigator by the ACRP
Certified Clinical Research Coordinator by the ACRP
Certified Clinical Research Professional by SoCRA
Member: The American College of Preventive Medicine

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