Celebrex Shown to be Safe for the Heart and Good for the Joints at Normal Doses

Non-Steroidal Anti-inflammatory Drugs (NSAIDs) are very common drugs, used in the treatment of all sorts of painful conditions, from a simple headache through to chronic 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 to lessen people’s pain. 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. Recently, a study was released that took the information obtained from lots of other studies, and combined all of their data to get a comprehensive look at the safety of these drugs. What the study found was that at the commonly used doses, Celebrex, a drug that has come to be used instead of Vioxx in many cases, is very safe and does not negatively impact the heart. The study also found that, 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 and pain.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. While older style NSAIDs stopped inflammation and pain, they also lowered the amount of these protective prostaglandins. The lowering of protective prostaglandins by old-style NSAIDS causes the lining to become irritated causing nausea, difficulty swallowing and, most severely, gastric ulcers. These can occasionally burst causing large amounts of bleeding. The gastrointestinal symptoms could be very severe, with a 5 to 6 times higher risk of hospitalization than a non-NSAID user, leading to 4,500 hospital admissions per year and up to 400 deaths. 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. Celebrex falls into this category of medication, as it is a COX-2 inhibitor; it dramatically reduces inflammation and pain while having very little damaging effect on the lining of the stomach. In fact Celebrex was so good, that it brings the risk of having a stomach ulcer bleed down to a level where it is equal to taking nothing at all, down 87.5% from taking a traditional NSAID.In 2004 however, studies showed that one other type of 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 type of article is what is known as a systematic review, where 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
• 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 at the doses of Celebrex that doctors would normally prescribe, for example in the reduction of arthritic pain, there is no increased risk of a heart attack than if someone were to be taking a sugar pill each day. While this does not mean that Celebrex is completely safe, because the study did not look at doses that are much higher than normally prescribed, for most people this will not be an issue and they can feel confident that Celebrex is not causing damage to their heart.This is great news for patients, as Celebrex is a very useful agent for many conditions. One of the major uses is in the treatment of osteoarthritis, a chronic condition in which the cartilage that lies within the joints starts to get damaged and inflamed causing pain on movement. In 2004, osteoarthritis affected 3.4 million Australians and was the leading cause of pain in the elderly, as well as the third leading cause of life-years lost due to disability.Celebrex has been shown to significantly reduce the pain seen in Osteoarthritis, with the effects starting in only around 30 minutes. It also shows a great increase in how much a patient is able to get around and conduct their everyday activities. The fact that this can now be achieved with the peace of mind that it will not negatively impact a patient’s heart at normally prescribed doses is great for those people suffering from pain – as well as for their doctors!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

1. McGettigan P, Henry D. A Systematic Review of the Observational Studies of Selective and Nonselective Inhibitors of Cyclooxygenase 2. JAMA. 2006;296(13):1633-44.