Although over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, naproxen, diclofenac, and ibuprofen, as well as selective cyclooxygenase-2 inhibitors, such as celecoxib, are commonly used to treat pain, these drugs cause about 100,000 hospitalizations and 17,000 deaths annually.

In fact, the U.S. Food and Drug Administration recently strengthened its warning about the risks of cardiovascular disease (CVD) attributed to NSAIDs.The risk of heart attack and stroke achieved special notoriety with rofecoxib (Vioxx), which caused as many as 140,000 heart attacks in the U.S. during the five years it was on the market. (Vioxx was removed from the market in 2004.)

The regrettable experience with Vioxx raised awareness about the cardiovascular risk of NSAIDs and led to further studies showing that the risk is not limited to Vioxx but is associated with all NSAIDs.

Because choosing a pain reliever can be complicated for healthcare providers and their patients, researchers from Florida Atlantic University’s Schmidt College of Medicine have addressed cardiovascular risks as well as gastrointestinal and kidney side effects of pain relievers, including over-the-counter and prescription drugs for pain relief. These include aspirin, ibuprofen (Motrin or Advil), naproxen (Aleve); prescription drugs such as diclofenac (Voltaren), a non-aspirin NSAID; and selective cyclooxygenase-2 inhibitors, such as celecoxib (Celebrex) and acetaminophen (Tylenol).

All these drugs have benefits and risks. Aspirin decreases inflammation as well as coronary events and stroke but increases gastrointestinal symptoms and bleeding, yet without adverse hepatic or renal consequences. Non-aspirin NSAIDs decrease inflammation but have been associated with adverse major coronary events and stroke with long-term use, major upper gastrointestinal and kidney side effects, and electrolyte imbalances, such as high sodium or potassium and even heart failure.

Cyclooxygenase-2 (COX2) inhibitors have a more favorable gastrointestinal side effect profile relative to aspirin and traditional non-aspirin NSAIDs but may cause adverse cardiovascular and hepatic and renal effects. Acetaminophen has no clinically relevant anti-inflammatory properties and accounts for more than 50% of drug overdose related liver failure and about 20% of liver transplant cases and kidney disease.

According to Manas Rane, M.D., a third-year internal medicine resident at Schmidt College of Medicine, healthcare providers and their patients should make individual clinical judgements based on the entire patient risk factor profile.

The factors in the decision of whether to prescribe an NSAID and, if so, which one for relief of pain from inflammatory arthritis should not be limited to risks of CVD or gastrointestinal side effects but should also include potential benefits, including improvements in overall quality of life resulting from decreases in pain or impairment from musculoskeletal pain syndromes.