Study into anti-inflammatory drugs shows celecoxib and ibuprofen do not increase cardiovascular risk at normal doses, but warns about diclofenac

Non-Steroidal Anti-inflammatory Drugs (NSAIDs) are very common drugs, used in the treatment of painful conditions such as arthritis. In October of 2004 it was revealed that one type of these drugs, rofecoxib (also known as Vioxx) was linked with a higher rate of cardiac problems such as heart attack. When this was revealed, it was removed from the market and other anti-inflammatory agents have been used. Since then, there has been some intensive research done to try and determine if other anti-inflammatory agents also increase the risk of heart attack or if it was just this one drug. This study took lots of other studies and combined all of their data to get a comprehensive look at all the information available and came to the conclusion that at commonly used doses, similar drugs such as celecoxib (also known as Celebrex) do not have a negative effect on the heart. Unfortunately one of the older agents, diclofenac, does appear to be associated with increased risk, which has prompted the authors to urge caution and further review of the regulations surrounding its use.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are incredibly useful drugs in many conditions as they reduce pain, fever and inflammation. The way NSAIDs work is by inhibiting an enzyme (a chemical that causes other chemical reactions to occur) called cyclooxygenase (sometimes referred to as COX). This enzyme is crucial for the inflammatory process to occur, and so by stopping the enzyme from working they stop inflammation. One of the unfortunate side effects of the early types of NSAID was that not only did they stop pain and inflammation but they also had effects on other parts of the body, most notably the lining of the stomach. On the stomach, cyclooxygenase creates protective chemicals called prostaglandins. When the NSAIDs stops the inflammation, it also lowers the amount of these protective prostaglandins. This can cause the lining to become irritated causing nausea, difficulty swallowing and, most severely, gastric ulcers that can occasionally bleed.However, the type of cyclooxygenase that protects the stomach lining (called COX-1) is very slightly different to the one that causes inflammation (called COX-2) and so drugs were developed to target only this COX-2 enzyme. Drugs that targeted only COX-2 are called ‘selective’ NSAIDs, while the older style ones are called ‘non-selective’. These selective drugs caused much less irritation to the stomach but still reduced pain and inflammation and so were used widely to treat long-term conditions like arthritis.In 2004 however, studies showed that one type selective NSAID, rofecoxib (or Vioxx) caused an increase in heart attacks and it was quickly removed from the market. Since then, people have been doing a lot of research into whether it was just Vioxx that increased cardiovascular risk or if it was all selective agents, or even all NSAIDS, that were the problem.A recent study was published in the Journal of the American Medical Association that provided new insight into this question. The article is what is known as a systematic review, and it looked into whether or not these drugs had any effect on the heart. In a systematic review, the authors take all the currently available evidence, judge each of the studies for their merits and combine their results to form new results. These are very useful types of studies because they have a lot more data than individual studies and can help to reduce any of the flaws that are found in individual studies. The authors read 233 articles on this issue of cardiac effects of NSAIDS and narrowed it down to 23 that they thought looked at exactly the features they wanted, and were of a high enough quality to be used. In total, this gave them 86,193 cases of cardiovascular events (usually a heart attack) and more than 528,000 ‘controls’ (people without heart problems or who did not take NSAIDs) to give a high quality of data.From all this data the found the following things:

• Rofecoxib (Vioxx) does definitely cause an increase in cardiovascular events, and the higher the dosage the higher the likelihood of an event
• Celecoxib (Celebrex – another selective COX-2 inhibitor) at the normal dose of 200mg/day did not increase risk, but this does not mean that at higher levels there is no increase
• An older agent, diclofenac (a non-selective NSAID), increased the rate of cardiac events, even at normal dosages
• Indomethacin (a non-selective NSAID) also increased the rate of cardiac events
• Naproxen, ibuprofen and piroxicam (all non-selective agents) did not appear to increase risk at normal doses
• Naproxen however, did not protect the heart as people had previously suggested

What this means is that while caution should still be used with celecoxib (Celebrex), at normal doses there does not appear to be a negative effect on the heart unlike the other selective agent rofecoxib (Vioxx). However, the large increase in events with the use of diclofenac has prompted the authors to state that they believe it should have its regulatory status reviewed. In the meantime, caution should be used with its prescription.If you have any questions or concerns regarding any part of this news item, ask your doctor for more information about the study and what it may mean for your medication regimen.References: