FANS: high dose consumption increases the risk of acute heart attack by up to 50%

NSAIDs: excessive use increases heart attack risk by up to 50%!

Excessive use of common non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen, dose-dependently increases the likelihood of acute myocardial infarction (heart attack). According to a recent international study, just one week of treatment with these drugs could increase the risk of heart attack by 20-50%, with the highest danger observed after 30 days.

The findings come from a meta-analysis conducted by researchers from the Universities of Montréal (Canada), Helsinki (Finland), and Bremen (Germany), and published in the prestigious British Medical Journal.

NSAIDs and heart attacks: an unclear link

NSAIDs are among the most widely used drugs worldwide due to their analgesic, antipyretic, and anti-inflammatory effects. Inflammation is a complex defense reaction of the body that helps the immune system intervene where damage occurs. However, inflammation can cause tissue damage, redness, swelling, pain, and fever.

The therapeutic effects of NSAIDs largely depend on their ability to inhibit prostaglandin synthesis, key chemical mediators of inflammation. Besides therapeutic actions, NSAIDs have numerous side effects, especially affecting the gastrointestinal tract, kidneys, and cardiovascular system.

For several years, it has been hypothesized that oral NSAIDs may increase the risk of acute myocardial infarction. Studies conducted so far to clarify this link have been insufficient, non-generalizable, and have provided imprecise and uncertain results. An exception is a study involving over 24,000 people, which found that the anti-inflammatory celecoxib, at moderate doses compared to ibuprofen and naproxen, may cause cardiac death, non-fatal myocardial infarction, or stroke in patients with arthritis and moderate cardiovascular risk.

Dosages and treatment duration in this and other studies may not reflect the clinical reality for many patients who use these drugs at lower, variable, or intermittent doses and often alternate one NSAID with another.

Continued use of high-dose NSAIDs can double the risk of heart attack

To clarify this controversial link, the researchers performed a meta-analysis to estimate the probability of acute myocardial infarction relative to various aspects of NSAID exposure, such as dose and duration of pharmacological treatment. Results revealed that the use of the most common NSAIDs is associated with a 20% to 50% increased risk of heart attack, with possible increases up to 75% for ibuprofen and naproxen.

Celecoxib was found to be the least dangerous. The research data also showed that the heart attack risk is dose-dependent, being higher in patients taking high doses, and increases already in the first week of therapy, peaking within the first month of treatment. Prolonged use beyond one month did not increase risks further compared to shorter periods.

According to the researchers, these findings suggest that doctors should carefully weigh risks and benefits before prescribing NSAIDs, especially in patients with heart problems or when high doses are required.

Key details of the research

For this meta-analysis, which compiles results from multiple studies, the researchers selected numerous scientific papers through Canadian and European databases, covering a total of 446,763 individuals, including 61,460 with acute myocardial infarction and 385,303 healthy controls.

All participants had taken varying doses of NSAIDs for one week, one month, or more than thirty days. Statistical data showed that daily treatments, regardless of duration, increased the probability of myocardial infarction.

Using NSAIDs for 1 to 7 days, the increased risk was 92% for celecoxib, 97% for ibuprofen, and 99% for diclofenac, naproxen, and rofecoxib. Specifically, the heart attack risk increased by 24% for celecoxib, 48% for ibuprofen, 50% for diclofenac, 53% for naproxen, and 58% for rofecoxib (no longer marketed in Italy). The danger was mainly related to high doses rather than treatment duration, peaking after the first month of administration.

Use for 8-30 days was particularly harmful at high daily doses of ibuprofen (over 1200 mg), naproxen (over 750 mg), and rofecoxib (over 25 mg). Celecoxib’s danger was comparable to that of traditional NSAIDs.

Conclusions still not definitive

Although this study considered several indicators of NSAID exposure, results are insufficient to precisely describe the impact on myocardial infarction risk, according to the authors. In particular, it was not possible to study the effect of NSAID doses taken before the treatment period considered, nor to determine the exact onset or duration of increased risk after stopping the drug.

According to Kevin McConway, professor of statistics at the Open University (UK), the findings shed light on possible relationships between common painkillers and heart attacks, but some aspects remain unclear. It could be hypothesized that NSAIDs do not cause heart attacks but that the attacks are caused by the conditions for which the drugs were prescribed. Also, the research only examined patients prescribed NSAIDs, not those who purchased them over the counter.

This meta-analysis is the largest of its kind, providing generalizable results thanks to the choice of populations studied and sample size. Thus, while the relationship between NSAID use and myocardial infarction needs further study, it allows conclusions on the dangers of dose and treatment duration, suggesting caution to doctors and, especially, patients who should take the minimum necessary NSAID doses for the shortest possible time without exceeding recommended amounts.

Source: Michèle Bally et al. Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data. British Medical Journal, 2017; 357