All NSAIDS Raise Risk of Heart Attack, Even When Taken For Short Period of Time Interview with:
Michèle Bally, BPharm, MSc, PhD

Epidemiologist, Department of Pharmacy, CHUM
Researcher, Health Innovation and Evaluation Hub, CRCHUM What is the background for this study?

Response: The objective of this study was to better understand the risk of heart attack associated with using oral prescription non-steroidal anti-inflammatory drugs or NSAIDs (ibuprofen, diclofenac, celecoxib, and naproxen) the way people usually do to treat pain and inflammation in real life circumstances.

In clinical trials, NSAIDs were typically taken on a continuous basis in high standardized doses, as assigned by the trial protocol. However, the dosages and the treatment durations studied in trials may not represent the reality of many patients who use NSAIDs in low or varying doses, use these drugs on and off, or switch between NSAID medications.

We were particularly interested in determining the onset of the risk, that is how soon does the risk of heart attack start increasing? Also, we wanted to investigate the effect of dose and duration of treatment. To do this, we studied the use of a low or high dose level of NSAIDs over certain set periods of time, including taking these medications only for 1 to 7 days. What are the main findings?

Response: The study found that all commonly prescribed NSAIDs – ibuprofen, diclofenac, celecoxib, and naproxen – were associated with an increased risk of heart attack.

This heightened risk of heart attack occurred as early as in the first week of use.

Risk of heart attack was greater with higher doses of NSAID.

Use of NSAIDs in the first month at a high daily dose (celecoxib >200 mg, diclofenac >100 mg, ibuprofen >1200 mg, and naproxen >750 mg) was associated with the greatest risk of heart attack.

With use of NSAIDs for longer than one month, this heightened risk did not seem to continue to increase even further. However, we did not study repeat heart attacks. How would you put this study in perspective?

Response: In general, people with heart disease or cardiac risk factors have a greater likelihood of heart attack following NSAID use than patients without these risk factors because they have a higher risk at baseline. People should be aware of their own baseline risk of heart disease and discuss use of NSAIDs with their healthcare providers, keeping in mind that on average the risk of a heart attack due to NSAIDs is only about 1% per year.

Overall, the study found that a person’s baseline risk of a heart attack is increased by about 20 to 50% with the use of common available NSAIDs. For most people, this represents only a small risk increase over a person’s baseline risk. However, from the viewpoint of public health, even small increases in risk of heart attack are important because use of NSAIDs is so widespread. What is the take home message for this study?

Response: NSAIDs are widely used to treat pain and inflammation from many different long-term conditions such as arthritis and other joint diseases and also for short-term problems such as menstrual cramps, fever from a cold or flu or the occasional backache or headache. Certain NSAIDs, ibuprofen and naproxen, are available for over-the-counter (OTC) purchase.

When making a choice to treat occasional pain, fever, or inflammation people may want to consider all available treatment alternatives as the increased risk of heart attack associated with NSAIDs may begin in the first 7 days of treatment. People should read the label of NSAID medications and should use the lowest possible effective dose.

People taking these drugs for a chronic painful condition may want to consider whether the benefit of increasing the dose for better relief outweighs a possible increased risk of heart attack. What else does this study bring?

Response: This study reveals a new finding, which is that for all common NSAIDs the risk of heart attack starts as early as in the first 1 to 7 days of use.

This study also confirms what was previously known, which is that possible risk of a heart attack may be greater if using higher doses of NSAIDs. We found that a heightened risk of heart attack persists with use of NSAIDs for longer than one month. Therefore, the results of our study support the previous guideline recommendations to use the lowest effective NSAID dose for the shortest possible time.

We studied more than 60,000 cases and our results were precise enough to conclude that the use of all common NSAIDs is associated with a heightened risk of heart attack. In this study, naproxen showed the same risk of heart attack as that for other NSAIDs. With celecoxib, the risk was lower than for rofecoxib (Vioxx) and was comparable to that of the traditional NSAIDs, ibuprofen, diclofenac, and naproxen. This is interesting because there is a perception in the scientific community that celecoxib is more toxic to the heart than are traditional NSAIDs and that naproxen, a traditional NSAID, has the lowest cardiovascular risk of all NSAIDs. Our study examined only heart attacks therefore no conclusion can be made about other cardiovascular risks that are known to be possibly associated with NSAIDs.

Drawing on experts in our group from the Department of Epidemiology at McGill University, we analyzed individual patient data using Bayesian methods. This approach gives probabilities of findings in a study. The data in our study allowed us to conclude with greater than 90% probability that all NSAIDs studied are associated with a heightened risk of heart attack. While this probability expresses the confidence in our results, our study is based on NSAID prescribing or dispensing and not all potentially influential factors could be taken into account. What recommendations do you have for future research as a result of this study?

Response: This work suggests that pooling deidentified patient data sourced from large administrative health or medical databases from many countries is useful for better understanding the real-world effects of medications. Pooling large populations is particularly helpful when studying a rare adverse drug event. Is there anything else you would like to add?
Response: In this study, we used data collected under real-life circumstances in a large number of patients from the general population, including older patients. This required accessing deidentified data that are coded to prevent a person’s identity from being connected with personal health information.

These health data are held in repositories called administrative health databases. Permission to access data was difficult to obtain, taking years or being denied altogether. Because of the many hurdles in getting access to data, our study took considerable time, a total of 10 years from the original idea to completion. Had we obtained the patient data for four additional studies that qualified for our analysis, we would have had 25% more cases of heart attack, which might have provided further guidance to health professionals and patients. Thank you for your contribution to the community.


BMJ publication:

Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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