Skip to content

A new study has been released that reminds us that all drugs (whether prescription or non-prescription) have side-effects.  This time a nation wide study from Denmark found that short-term use of the non-steroidal anti-inflammatory drugs (NSAIDs) ibuprofen (e.g. Advil and Motrin) and diclofenac is linked to a higher risk of cardiac arrest (the heart suddenly stops beating). It was an observational study so can't definitely say that ibuprofen and diclofenac caused the cardiac arrests, but the findings match a growing body of evidence.

Since Ibuprofen and other NSAIDs are popular non-prescription medicines used worldwide, people assume they are safe to use. In Denmark, ibuprofen is the only NSAID sold as an over-the-counter drug, and only in small amounts. In the U.S., both ibuprofen and diclofenac are sold in both non-prescription and prescription forms.

In the study, they found an increased risk of cardiac arrest in ibuprofen and diclofenac users. However, they did not find a risk of cardiac arrest with the use of COX-2 selective inhibitors, rofecoxib and celecoxib, nor with the NSAID naproxen. One of the researchers (Dr. Gislason) therefore advises consumers to try to avoid diclofenac, to limit the use of ibuprofen to no more than 1200 mg per day, and that perhaps the safest is naproxen (up to 500 mg per day). From Medical Xpress:

'Harmless' painkillers associated with increased risk of cardiac arrest

Painkillers considered harmless by the general public are associated with increased risk of cardiac arrest, according to research published today in the March issue of European Heart Journal - Cardiovascular Pharmacotherapy.....The current study investigated the link between NSAID use and cardiac arrest. All patients who had an out-of-hospital cardiac arrest in Denmark between 2001 and 2010 were identified from the nationwide Danish Cardiac Arrest Registry. Data was collected on all redeemed prescriptions for NSAIDs from Danish pharmacies since 1995. These included the non-selective NSAIDs (diclofenac, naproxen, ibuprofen), and COX-2 selective inhibitors (rofecoxib, celecoxib).

A total of 28 947 patients had an out-of-hospital cardiac arrest in Denmark during the ten year period. Of these, 3 376 were treated with an NSAID up to 30 days before the event. Ibuprofen and diclofenac were the most commonly used NSAIDs, making up 51% and 22% of total NSAID use, respectively. Use of any NSAID was associated with a 31% increased risk of cardiac arrest. Diclofenac and ibuprofen were associated with a 50% and 31% increased risk, respectively. Naproxen, celecoxib and rofecoxib were not associated with the occurrence of cardiac arrest, probably due to a low number of events.

"The findings are a stark reminder that NSAIDs are not harmless," said Professor Gislason. "Diclofenac and ibuprofen, both commonly used drugs, were associated with significantly increased risk of cardiac arrest. NSAIDs should be used with caution and for a valid indication. They should probably be avoided in patients with cardiovascular disease or many cardiovascular risk factors." NSAIDs exert numerous effects on the cardiovascular system which could explain the link with cardiac arrest. These include influencing platelet aggregation and causing blood clots, causing the arteries to constrict, increasing fluid retention, and raising blood pressure. [Original study.]

 Some recent studies looked at aspirin use and cancer and found that consistent use for a number of years (5 to 10 years) lowers the rate of a number of cancers, including colon cancer. However, the longer one takes daily aspirin - then harms start adding up, with a major one being gastrointestinal bleeding. NSAIDs (non-steroidal anti-inflammatory drugs) are also linked to lower rates of various cancers, but harms with long-term use are cardiovascular risks (stroke and heart attack). The first article discusses that many doctors think this lower cancer rate occurs because aspirin and NSAIDs lower inflammation, and as we know, inflammation is linked to cancer.

From Science News: Aspirin reverses obesity cancer risk

Research has shown that a regular dose of aspirin reduces the long-term risk of cancer in those who are overweight in an international study of people with a family history of the disease....They found that being overweight more than doubles the risk of bowel cancer in people with Lynch Syndrome, an inherited genetic disorder which affects genes responsible for detecting and repairing damage in the DNA. Around half of these people develop cancer, mainly in the bowel and womb. However, over the course of a ten year study they found this risk could be counteracted by taking a regular dose of aspirin.

 Lots of people struggle with their weight and this suggests the extra cancer risk can be cancelled by taking an aspirin.This research adds to the growing body of evidence which links an increased inflammatory process to an increased risk of cancer. Obesity increases the inflammatory response. One explanation for our findings is that the aspirin may be suppressing that inflammation which opens up new avenues of research into the cause of cancer."

When they were followed up ten years later, 55 had developed bowel cancers and those who were obese were more than twice as likely to develop this cancer -- in fact 2.75 times as likely. Following up on patients who were taking two aspirins a day revealed that their risk was the same whether they were obese or not....What is surprising is that even in people with a genetic predisposition for cancer, obesity is also a driver of the disease. 

The researchers believe the study shows that aspirin is affecting an underlying mechanism which pre-disposes someone to cancer and further study is needed in this area. Since the benefits are occurring before the very early stages of developing a tumour -- known as the adenoma carcinoma sequence -- the effect must be changing the cells which are predisposed to become cancerous in later years.

From Medical Xpress:  Low-dose aspirin, other painkillers may lower colon cancer risk

Regularly taking low-dose aspirin or other common pain relievers may lower long-term risk of colon cancer, new research suggests. Men and women who took low-dose (75 to 150 milligrams) aspirin for five years or more saw their risk of colon cancer drop by 27 percent. And taking non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen for that long was linked to a 30 percent to 45 percent drop in colon cancer risk, the study found.

The study did not assess the potential impact of high-dose aspirin, and no protective benefit was seen for irregular or short-term users of either low-dose aspirin or other NSAIDs.And the study did not prove that the use of painkillers reduced the risk of colon cancer, just that there was an association between the two. In the United States, NSAIDs include over-the-counter Aleve (naproxen), Advil and Motrin (both ibuprofen), and prescription drugs such as Celebrex and high-strength Motrin.

Baron emphasized that the drugs were taken continuously for years before any cancer-preventive benefits were realized. "For aspirin, you would have to take it fairly consistently, meaning at least every other day, for at least five to 10 years for the protective effect to even begin to appear," he said."That's a significant amount of time for side effects to accumulate, all without getting any benefit," he said. Potential side effects include gastrointestinal bleeding with aspirin, and heightened risk for heart attack and stroke with long-term use, or high-dose use, of NSAIDs, according to the U.S. Food and Drug Administration.

A comparison of cancer patients with more than 100,000 cancer-free Danes revealed that regular, long-term use of low-dose aspirin and NSAIDs seemed to confer long-term protection against colon cancer. The biggest benefit was linked to NSAIDs with the highest degree of so-called COX-2 selectivity. Celebrex is one such drug. That said, the U.S. Food and Drug Administration requires a "black box" warning—its strongest drug-related warning—on Celebrex packaging to alert users to the heightened risk for heart attack or stroke.

More from Medscape:  Nonaspirin NSAIDs Match Aspirin on Cancer Protection

A 2014 study mentioned in the Medscape article. They also discuss in-depth about who should not take long-term aspirin. From Annals of Oncology: Estimates of benefits and harms of prophylactic use of aspirin in the general population

Accumulating evidence supports an effect of aspirin in reducing overall cancer incidence and mortality in the general population. We reviewed current data and assessed the benefits and harms of prophylactic use of aspirin in the general population.

The effects of aspirin on cancer are not apparent until at least 3 years after the start of use, and some benefits are sustained for several years after cessation in long-term users. No differences between low and standard doses of aspirin are observed, but there were no direct comparisons. Higher doses do not appear to confer additional benefit but increase toxicities. Excess bleeding is the most important harm associated with aspirin use, and its risk and fatality rate increases with age. For average-risk individuals aged 50–65 years taking aspirin for 10 years, there would be a relative reduction of between 7% (women) and 9% (men) in the number of cancer, myocardial infarction or stroke events over a 15-year period and an overall 4% relative reduction in all deaths over a 20-year period.

Prophylactic aspirin use for a minimum of 5 years at doses between 75 and 325 mg/day appears to have favourable benefit–harm profile; longer use is likely to have greater benefits...It should also be recognised that our best estimates may be conservative, as bigger effects have been seen in several studies, and the overview of trials with long-term follow-up found a 20% relative mortality reduction in all cancers.

Although often not as serious as MI, stroke or cancer for the age groups considered here, major bleeding is the most important serious side-effect of aspirin.... Clear contraindications are those with peptic ulcer, recent bleeding episodes or bleeding tendencies. Other risk factors for bleeding in aspirin or non-steroidal anti-inflammatory drug (NSAID) users are: increasing age, male sex, diabetes, hypertension, being overweight or obese, smoking, alcohol consumption and H. pylori infection .