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

NSAIDs: immoderate consumption increases heart attack risk by up to 50%!

Overconsumption of common nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen, dose-dependently increases the likelihood of acute myocardial infarction. According to the reports of a recent international study, a single week of treatment with these drugs would be enough to increase the risk of heart attack by 20-50%, with a maximum of dangerousness after 30 days.

The findings are those of a meta-analysis conducted by researchers at the Universities of Montréal (Canada), Helsinki (Finland) and Bremen (Germany), and published in the prestigious journal BritishMedicalJournal.

NSAIDs and heart attack: still an unclear link

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs in the world because of their analgesic, antipyretic, and anti-inflammatory effects. Inflammation is a complex defense reaction of the body that encourages the immune system to intervene at sites where damage occurs. However, the inflammatory process can cause tissue damage, redness, swelling, pain, and fever. 

The therapeutic effects of NSAIDs depend largely on their ability to inhibit the synthesis of prostaglandins, among the main chemical mediators of inflammation. In addition to their curative actions, nonsteroidal anti-inflammatory drugs also have numerous side effects, especially gastrointestinal, renal, and cardiovascular. 

For some years, the hypothesis has emerged that oral NSAIDs may increase the risk of acute myocardial infarction. Studies conducted to clarify this link have so far been insufficient, nongeneralizable, and have provided imprecise and uncertain results. An exception is a study that involved more than 24,000 people and filled in some of these gaps, finding that the anti-inflammatory celecoxib, in moderate doses compared with ibuprofen and naproxen, can cause cardiac death, nonfatal myocardial infarction, or stroke, in subjects with arthritis and moderate cardiovascular risk.

 The dosages and duration of treatment in this and other studies, however, may not represent the clinical reality of many patients who use these drugs in lower doses than studied, variable or intermittent, and often substitute one anti-inflammatory for another.

Continued use of high doses of NSAIDs can double the risk of heart attack

Aiming to clarify this controversial link, the team of researchers performed a meta-analysis to estimate the probability of acute myocardial infarction in relation to different aspects of NSAID exposure, such as dose and duration of drug treatment. The results revealed that the use of the most common anti-inflammatory drugs is associated with a 20% to 50% increased risk of heart attack, with possible increases of 75% in the case of ibuprofen and naproxen. 

The one that was found to be less dangerous was celecoxib. The research data also revealed that the risk of heart attack was dose-dependent, in that it was greater in patients who took high dosages, and increased as early as the first week of therapy, peaking in the first month of treatment. In the case of prolonged use for more than one month, the risks were no greater than those associated with shorter periods. 

This evidence, according to the researchers who conducted the study, suggests how physicians should, before prescribing NSAID therapies, carefully consider the risks and benefits, especially in the case of patients with heart problems, or in circumstances that require high-dose drugs.

Some main details of the research

To carry out the meta-analysis, which takes into account the set of results from other studies, the researchers selected numerous scientific papers through appropriate Canadian and European databases, with a total of 446,763 individuals, including 61,460 suffering from acute myocardial infarction and 385,303 healthy subjects as controls. 

All people included in the research had taken varying dosage of nonsteroidal anti-inflammatory drugs for one week, one month or more than thirty days. According to the statistical data obtained, daily treatments regardless of duration caused the increased likelihood of myocardial infarction. 

With NSAID use from 1 to 7 days, the probability of increasing this risk was found to be 92% for celecoxib, 97% for ibuprofen, and 99% for diclofenac, naproxen, and rofecoxib. In detail, the increased risk of heart attack was 24% for celecoxib, 48% for ibuprofen, 50% for diclofenac, 53% for naproxen, and 58% for rofecoxib, the latter not on the market in Italy. In addition, it was found that the hazard is mainly related to high dosages, and less to the duration of treatment, peaking after the first month of administration.

Use for 8-30 days is particularly harmful for high daily doses of ibuprofen (greater than 1200 milligrams), naproxen (greater than 750 milligrams) and rofecoxib (greater than 25 milligrams). The hazard of celecoxib was found to be comparable to that of traditional NSAIDs.

Conclusions still not final

Although this study considered a number of indicators on NSAID exposure, the results are insufficient to accurately describe the impact on the risk of myocardial infarction, the authors themselves commented. In particular, it was not possible to study the effect of the doses of anti-inflammatory drugs consumed prior to the treatment considered in the study, nor was it possible to know the precise onset of the increased risk or the duration of the increased risk after the drug was discontinued. 

According to Kevin McConway, professor of statistics at the U.K.'s Open University, the finding has shed light on possible relationships between the most common painkillers and heart attacks, but some aspects remain unclear. For example, one could speculate that NSAIDs do not cause heart attacks, but that this is caused by the disorder for which the drugs were prescribed. It should be kept in mind that the research examined only patients who consumed anti-inflammatory drugs under prescription and did not take into account all those subjects who purchased them independently. 

This meta-analysis is the largest investigation of its kind, and it provides generalizable results due to the choice of study populations and sample size. Thus, although the relationship between the use of NSAIDs and myocardial infarction needs to be further investigated, it does allow conclusions to be drawn about the dangerousness of doses and timing of treatment, suggesting caution to physicians but, more importantly to patients that they should take minimal amounts of NSAIDs for the shortest possible time and without exceeding what is indicated.  

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