Studies have shown that people who take anti-inflammatory painkillers have a small but significant increase in the risk of developing a heart attack or stroke . Although it can occur in anybody, the risk is mainly in people already known to have cardiovascular problems such as angina or peripheral arterial disease , and in the elderly. Perhaps the highest risk is in people who have previously had a heart attack. For example, one research study looked at people who had previously had a heart attack. The results showed a marked increase in the rate of a second heart attack in people who were taking an anti-inflammatory compared to those who were not.
NSAIDs have anti-inflammatory (reduce inflammation), analgesic (relieve pain) and antipyretic (lower temperature) effects. Although different NSAIDs have different structures, they all work by blocking cyclooxygenase (COX) enzymes. There are two main types of COX enzymes: COX-1 and COX-2. Both types produce prostaglandins; however, the main function of COX-1 enzymes is to produce baseline levels of prostaglandins that activate platelets and protect the lining of the gastrointestinal tract, whereas COX-2 enzymes are responsible for releasing prostaglandins after infection or injury. Prostaglandins have a number of different effects, one of which is to regulate inflammation. Most NSAIDs inhibit both enzymes, although a few are available that mainly inhibit COX-2. The pain-relieving and anti-inflammatory effects of NSAIDs are mainly due to inhibition of COX-2, and their unwanted side effects are largely due to inhibition of COX-1.
In studies lasting 6 to 12 weeks, topical diclofenac and topical ketoprofen were significantly more effective than carrier for reducing pain; about 60% of participants had much reduced pain. With topical diclofenac, the NNT for clinical success in six trials (2343 participants) was (95% confidence interval ( CI ) to 16) (moderate quality evidence). With topical ketoprofen, the NNT for clinical success in four trials (2573 participants) was ( to ) (moderate quality evidence). There was too little information for analysis of other individual topical NSAIDs compared with carrier. Few trials compared a topical NSAID to an oral NSAID , but overall they showed similar efficacy (low quality evidence). These efficacy results were almost completely derived from people with knee osteoarthritis.