Heart attack risks from common painkillers may start early, study finds

People taking commonly prescribed anti-inflammatory painkillers may face a very small increased risk of heart attack as early as a week after starting the medications, an international study led by a Quebec researcher suggests.

Non-steroidal anti-inflammatory drugs, or NSAIDs, are taken to reduce pain, stiffness and inflammation.

In Canada, Ibuprofen is sold in 200-milligram form off the shelf under brands including Advil and Motrin. Ibuprofen is available in higher doses with a prescription, as are the other NSAIDs studied:

• Diclofenac.
• Naproxen.
• Celecoxib (sold as Celebrex and other forms).
• Rofecoxib (Vioxx).

When Merck pulled Rofecoxib from the market worldwide in 2004 because it may cause an increased risk in cardiovascular events such as heart attacks and strokes with chronic use, doctors, patients and pharmacists were left with questions about the heart risks of all NSAIDs.

Now epidemiologist Michèle Bally of the University of Montreal Hospital Research Centre and her colleagues have analyzed individual, anonymous patient data on 446,763 people in Quebec, Saskatchewan, Finland and England, including 61,460 who had a heart attack (first myocardial infarction), to take a close look at the risks of NSAID use.

The heart attack findings reinforce why consumers should read the label on NSAIDs and talk to a health-care professional before using any, says Michèle Bally of the University of Montreal Hospital Research Centre. (University of Montreal)

In clinical trials, participants are usually assigned to take high doses of medications continuously.

Bally was interested in exploring the heart attack risks in real life associated with such factors as various doses, on-and-off use and switching medications.

“We thought it was important to look at the risk associated with very short-term use, one to seven days, because that risk was not documented previously.”

In Tuesday’s issue of The BMJ (formerly the British Medical Journal), Bally and her team from McGill University, Finland and Germany say the risk of heart attack appeared greatest in the first month of treatment with higher doses.

“Prescribers should consider weighing the risks and benefits of NSAIDs before instituting treatment, particularly for higher doses,” the authors wrote.

Since the meta-analysis was based on observational data from administrative databases and no one was assigned a treatment, no cause-and-effect conclusions can be drawn.

In 2015, the U.S. Food and Drug Administration and Health Canada warned of serious heart attack and stroke risks associated with NSAIDs.

Benign perception 

For Bally, the findings reinforce why consumers need to read NSAID drug labels and talk to their doctor.

“There’s a perception that they’re benign,” Bally said. “Please read the label. Be aware and ask your doctor about your cardiovascular baseline risk.”

Bally gives the example of a one per cent risk of heart attack per year due to NSAIDs in an elderly individual with Type 2 diabetes who smokes, has hypertension and a previous heart attack and takes NSAIDs continuously for aches and pains.

 “Our study suggests that one per cent increases to 1.2 per cent per year or 1.5 per cent per year. That’s very low from a single person’s viewpoint. It will be like 12 people out of 1,000 or 15 people out of 1,000.”

Dr. David Henry has studied the impacts of medication use at the University of Toronto. He was not involved in the study, which he called a “very sophisticated approach to analyzing individual patient data” that emulates a large clinical trial.

“The results confirm the overall risk with NSAIDs and show its very rapid onset,” Henry said in an email.

“The recommendation to avoid in the highest-risk patients and use the lowest dose still stands. For the general public without a history and without major risk factors the risk remains very low — that hasn’t changed.”

Heart risks ‘fairly similar’

The research was ambitious, said Muhammad Mamdani, a scientist at the Li Ka Shing Centre at St. Michael’s Hospital and a pharmacy professor at the University of Toronto.

“Where this study is useful is that if you’re thinking about one drug over another, I wouldn’t be too concerned about picking which one in terms of the ones that are available on the market because they seem be fairly similar,” Mamdani said.

For Mamdani, the jury is still out on whether NSAIDs actually cause an increase in heart attacks, in part because it’s so difficult to compare NSAID users and non-users. NSAIDs are also associated with gastro-intestinal and kidney risks.

“The key point is go to your physician and make sure you actually need one of these things,” Mamdani said. “If you’re having pain, is it because you have arthritis or is it because you have fibromylagia? Maybe you don’t even need to take an NSAID. Maybe there are other things that you should be treated with.”