When taking an evidence-based approach to the use of any drug, we must consider three factors:
1. What beneficial effects do we want the drug to have on our patients?
2. What harm might the drug cause? How can we maximize benefit while minimizing risk?
3. How much does the drug cost? Can we get a better risk/benefit profile from a less expensive
    drug? 

A great place to start using these tools to evaluate drug use is with nonsteroidal anti-inflammatory drugs. NSAIDs are commonly prescribed, but we practitioners tend to use them in inappropriate ways. We overestimate the benefit they give. We underestimate the risks they carry. We completely ignore their costs, preferring, it seems, to prescribe expensive NSAIDs that offer no benefits over the cheap stuff.

NSAIDs are a very well-understood class of medications with a large body of research. Most of the information provided in this article is not controversial and can be found in most textbooks and review articles. This article will summarize the evidence about NSAIDs and suggest a protocol for their use based on that evidence. [See "For Further Reading" for citations of two excellent review articles.]

Potential Harm
Let’s start with the potential harm NSAIDs can cause. Most people know they can cause gastrointestinal complications such as ulcers and bleeding. The question is, how big of a problem is this? Very big, indeed.

Over 100,000 people are hospitalized each year with GI complications caused by NSAID use, and an estimated 16,500 patients die from NSAID-induced GI bleeding. This is far more people than die of AIDS (13,500). In fact, such GI bleeding is the 14th leading cause of death in this country, according to the CDC.

NSAIDs have other potential complications, too. Patients risk renal failure. The COX-2 inhibitors increase the risk of cardiovascular complications, as we learned when Vioxx was pulled from the market.

The iatrogenic cost factor of NSAID use is approximately 2. In other words, for every dollar spent on NSAIDs, one more dollar is spent treating NSAID-induced complications. Total U.S. spending to treat NSAID complications exceeds $2 billion per year.

Drug Benefits
The second way to reduce risk is to understand the relation between the risk of complications and the benefit NSAIDs give.

NSAIDs have two basic uses: to relieve pain and to reduce inflammation. Looking first at analgesic effects, these drugs are equivalent. No NSAID has ever been shown to be superior to another.

Also, the analgesic effects “max out” at a much lower dose than the anti-inflammatory effects. With ibuprofen, for example, the pain-relieving properties max out at a dose of 200 mg to 400 mg, depending on the patient’s size. Ibuprofen 800 will provide no increased analgesic effect compared to a 400 mg dose.

Now let’s discuss anti-inflammatory properties. Here, increasing dose and increasing length of NSAID exposure will also increase the anti-inflammatory effect—and the potential for complications.

We may tell ourselves we need to use a larger dose because we are treating “inflammation.” For the most part, we are deluding ourselves. Few acutely painful conditions that we treat with NSAIDs are truly inflammatory. Even chronic painful conditions will most likely not be amenable to treatment with anti-inflammatory doses of NSAIDs. To provide one example, osteoarthritis is not an inflammatory condition.

The bottom line: NSAIDs are no better than acetaminophen for musculoskeletal pain and osteoarthritis. NSAIDs are not effective for chronic musculoskeletal conditions.

The obvious message is that when we use NSAIDs, we should be using smaller doses for the shortest length of time possible.

COX-2 Inhibitors
Another issue to consider relates to  the COX-2 inhibitors. These have been some of the most heavily (and successfully) marketed drugs in history. The marketing message has been that COX-2 inhibitors cause fewer GI side effects than nonselective NSAIDs and therefore are safer.

It turns out that this message is both misleading and outright false. First, it is debatable whether the COX-2 inhibitors have any real benefit over other NSAIDs with regard to serious GI side effects such as serious bleeding. If they do, the effect is small and evident only after months of continuous usage—which is not the case for the majority of patients for whom these drugs are prescribed.

What has not been fully reported to doctors is that if you look at all serious complications, including death, MIs, heart failure, kidney failure, etc., the COX-2 inhibitors have consistently been shown to have an increased risk compared to other NSAIDs. So no matter how you spin it, COX-2 inhibitors are more dangerous, not less, than other NSAIDs.