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.
Formulations of topical diclofenac, ibuprofen, ketoprofen, piroxicam, and indomethacin demonstrated significantly higher rates of clinical success (more participants with at least 50% pain relief) than matching topical placebo (moderate or high quality data ). Benzydamine did not. Three drug and formulation combinations had NNTs for clinical success below 4. For diclofenac, the Emulgel® formulation had the lowest NNT of (95% CI to ) in two studies using at least 50% pain intensity reduction as the outcome . Diclofenac plasters other than Flector® also had a low NNT of ( to ) based on good or excellent responses in some studies. Ketoprofen gel had an NNT of ( to ), from five studies in the 1980s, some with less well defined outcomes. Ibuprofen gel had an NNT of ( to ) from two studies with outcomes of marked improvement or complete remission. All other drug and formulation combinations had NNT values above 4, indicating lesser efficacy .