They reviewed 82 studies to identify patients pooled from national universal healthcare datasets and did a meta-analysis of individual patient data for 446,763 patients aged 40 to 79 years. Of those patients, 61,460 had an MI. 

Increased risk for MI was associated with the use of all NSAIDs and began immediately after exposure — often within 1 to 7 days.

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Further, they found that higher doses of NSAIDs, regardless of the NSAID used, was associated with an overall greater risk for MI. In fact, they noted a 50% increase in risk over the 8 to 30 days following its use among patients taking the higher doses of NSAIDs. 

High-dose was defined as 1200 mg per day of ibuprofen, 750 mg per day of naproxen, and >25 mg per day of rofecoxib.2 The study authors also found that while exposure to an NSAID was sufficient to increase MI risk, the risk did not increase further for longer durations of therapy.2

This is alarming, given that both ibuprofen and naproxen are the workhorse pain relievers for musculoskeletal injuries and inflammatory conditions. Even more alarming is that both drugs are available over-the-counter (OTC) at daily doses that meet or exceed high-dose as defined by the study — and many patients incorrectly believe that OTC means “safe to use.”

In my practice, I warn my patients, with atherosclerotic heart disease or heart failure, to stay away from NSAIDs. However, Dr Bally’s study suggests that even those without prior heart disease should be cautious. In a world where opioid use is rampant, avoiding non-habit–forming alternatives such as NSAIDs becomes particularly challenging.

For pharmaceutical companies, this may be an opportunity for research and development into newer anti-inflammatory agents that pose less cardiovascular risk. 

As physicians, it may be more prudent to recommend physical therapy for pain relief whenever possible and to suggest exploring alternative therapeutic modalities, such as massage therapy and acupuncture. In either case, patients should be advised of the risks associated with NSAID use and weigh their discomfort against the potential risk of having a heart attack or stroke.


  1. Non-Aspirin Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): Drug Safety Communication — FDA Strengthens Warning of Increased Chance of Heart Attack or Stroke. US Food & Drug Administration. Updated July 09, 2015. Available at: ucm454141.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery. Accessed May 30, 2017.
  2. Bally, Michèle, et al. “Risk of Acute Myocardial Infarction with NSAIDs in Real World Use: Bayesian Meta-Analysis of Individual Patient Data.”  BMJ. 2017;357: j1909. doi: 10.1136/bmj.j1909

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