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NSAIDs (Advil, Aleve, Vioxx...) increases risk of first heart attack

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Nonsteroidal anti-inflammatory drugs, or NSAIDS, are assumed to be well tolerated and are widely used as a therapy for common pain and conditions such as arthritis. These pharmaceuticals constitute one of the most widely used class of drugs, with more than 70 million prescriptions and more than 30 billion over-the-counter tablets sold annually in the United States alone. NSAIDs are called nonsteroidal because they are not steroids. Steroids affect inflammation by suppressing part of the immune system, which is the body's natural healing response to trauma. Instead NSAIDs mainly inhibit the body's ability to synthesize prostaglandins. Prostaglandins are a family of hormone-like chemicals, some of which are made in response to cell injury.

Unfortunately, prostaglandins are also involved in the healing mechanism of the digestive system and because NSAIDs affect prostaglandins they have the unwanted side effect of increasing the possibility of gastrointestinal bleeding. According to the American Journal of Medicine, "Conservative calculations estimate that approximately 107,000 patients are hospitalized annually for nonsteroidal anti-inflammatory drug (NSAID)-related gastrointestinal (GI) complications and at least 16,500 NSAID-related deaths occur each year among arthritis patients alone. The figures of all NSAID users would be overwhelming, yet the scope of this problem is generally under-appreciated." These conservative figures are equivalent to 293 hospitalizations and 45 deaths each day from NSAID GI complications in U.S. arthritis patients alone.

The New England Journal of Medicine also stated "If deaths from gastrointestinal toxic effects from NSAIDs were tabulated separately in the National Vital Statistics reports, these effects would constitute the 15th most common cause of death in the United States. Yet these toxic effects remain mainly a 'silent epidemic,' with many physicians and most patients unaware of the magnitude of the problem. Furthermore the mortality statistics do not include deaths ascribed to the use of over-the-counter NSAIDS."

Still more shocking is that according to the Canadian Medical Association Journal, "All NSAIDs, both COX-2 selective and nonselective, provide only a modest symptomatic benefit over placebo, and this benefit has been proven only in short-term trials. With long-term therapy, it is not known whether the benefits of this class of drugs exceed the harms." And although COX-2 selective NSAIDs were developed on the theory of reduced patient problems the same study in the Canadian Medical Association Journal, states, "COX-2 selective NSAIDs do not necessarily reduce the incidence of complicated ulcers. Second, the meta-analysis demonstrates that, rather than proving safer, COX-2 selective NSAIDs cause more morbidity (total SAEs or Serious Adverse Events) than nonselective NSAIDs."

In addition to now being found increasingly just how dangerous these medications are and that they have been only slightly more beneficial than sugar pill, a recent study in British Medical Journal (BMJ) notes that, "as NSAIDs were originally developed for the relief of pain, long term placebo controlled trials have not been done."

On top of the horrifying gastrointestinal problems it has become increasingly clear that these medications also have serious cardiovascular risks. In the recent documentary Prescription for Disaster, we hear former Associate Director for Science and Medicine at the Office of Drug Safety at the U.S. Food and Drug Administration (FDA) turned whistle blower David J. Graham, MD, MPH testify before Congress in November 2004 on the Vioxx disaster. "Vioxx is a profound tragedy and a regulator failure. We're faced with maybe the single greatest drug safety catastrophe in the history of this country. I strongly believe this should have been and largely could have been avoided, but it wasn't and over 100,000 Americans have paid dearly for this failure. In my opinion the FDA has let the American people down."

A May 2006 study in the European Heart Journal examines the relationship between NSAID use and the risk of a heart attack. They performed a large population based study on over 33,000 people who had a first heart attack also termed Myocardial Infarction or MI for short.

The authors found "a clear but moderate association (less than two-fold) between first MI and current use of NSAIDs." The association between first heart attack and NSAID existed in conventional, semi-selective, and COX-2 NSAIDs. The risk of first heart attack varied widely with celecoxib (Celebrex ) having the lowest at an increased risk of 6% and etoricoxib (Arcoxia ) having a huge increased risk of 121%. The risks for first heart attack were as follows:

Conventional NSAIDs:

Indomethacin (Indocin ) - 56%
Ibuprofen (Advil ) - 41%
Diclofenac (Voltaren ) - 35%
Naproxen (Aleve ) - 19%
Piroxicam (Feldene ) - 35%
Ketoprofen (Orudis , Oruvail ) - 11%
Tolfenamic Acid - 39%
Other conventional NSAIDs - 23%

Semi-selective NSAIDs:

Nimesulide - 69%
Etodolac (Lodine ) - 35%
Nabumetone (Relafen ) - 26%
Meloxicam (Mobic ) - 24%


Etoricoxib (Arcoxia ) - 121%
Rofecoxib (Vioxx ) - 44%
Celecoxib (Celebrex ) - 6%
Multiple NSAIDs - 56%

The study also shows that even after stopping taking NSAIDs users still have increased risk of heart attack for a month after stopping. However, after a month the risk of first heart attack was decreased to normal. "Our findings clearly indicate that the risk is reversible and associated with the presence of the drug in the body; the closer the proximity of the prescription, the larger the effect."

The authors conclude, "The present large population-based case-control study demonstrated a modest association of MI with current use of all NSAIDs."

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