Painkillers: How common are severe side effects of NSAIDs?

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Painkillers from the NSAID class such as ibuprofen and diclofenac can cause serious side effects like gastric ulcers and bleeding. This risk can be reduced considerably by taking medicine to protect the lining of the stomach. Certain painkillers also increase the risk of cardiovascular disease, especially when taken for a longer time and at a higher doses.

Anti-inflammatory painkillers from the NSAID group are some of the most commonly used medications. Their most frequent complications are gastritis, ulcers and bleeding in the stomach or bowel (gastrointestinal tract). At the start of this century multiple signs were found that certain NSAIDs could increase the risk of cardiovascular disease such as heart attacks. But that isn’t true of acetylsalicylic acid (the drug in Aspirin, also called ASA). ASA actually lowers the risk of platelets clumping together and blocking blood vessels. For this reason ASA is used at low doses to prevent heart attacks.

The risk of complications from NSAIDs depends on various factors, such as the dose of the medication, how long it is taken for, and other, pre-existing risks and diseases. To reduce the risk of complications, it’s a good idea to take the painkillers at the lowest possible dose and only to use them for as long as necessary.

Risk of cardiovascular disease

High dose

An international group of researchers analyzed several hundred treatment studies on commonly used NSAIDs in order to better assess the risk of complications affecting the heart and circulatory system. They looked at how often the medications caused these kinds of complications.

Most of the people who participated in the studies had osteoarthritis or rheumatoid arthritis and were about 60 years old. They took the medications at very high doses:

  • Diclofenac: 150 mg per day
  • Ibuprofen: 2,400 mg per day
  • Naproxen: 1,000 mg per day

The research group calculated how often fatal and non-fatal heart attacks, strokes and other cardiovascular-related deaths can be expected when 1,000 people take NSAIDs for a period of one year. Their analysis shows that those kinds of complications affected 2 to 9 of the 1,000 people who took diclofenac or ibuprofen.

Naproxen didn’t increase the risk of cardiovascular disease in the studies, though.

Low dose

Many people take painkillers at lower doses. Do NSAIDs also increase the risk of cardiovascular disease then? Another group of researchers looked into this question, and analyzed over 50 studies.

The results show that ibuprofen isn’t associated with a higher risk of cardiovascular disease when taken at a dose of less than 1,200 mg per day. This risk was still higher in people who took diclofenac in doses of less than 100 mg per day, but to a lesser extent.

Duration of use

It’s not known at exactly what point in time the use of NSAIDs starts to increase the risk of cardiovascular disease. Most of the studies that were analyzed involved people who took NSAIDs for at least four weeks. There is that the risk may increase after shorter use of less than two weeks, at least in people who already have some kind of heart disease.

Risk of gastrointestinal complications

The first group of researchers also looked into how often NSAIDs cause rare but serious complications affecting the gastrointestinal tract. These complications particularly include bleeding, but also perforations of the wall of the stomach or bowel and obstruction of the bowel.

All of the NSAIDs may cause these complications. The analysis of the studies on the frequency of complications affecting the gastrointestinal tract shows that within one year

  • this type of complication occurs in 2 to 4 out of 1,000 people who take diclofenac (150 mg per day).
  • this type of complication occurs in 6 to 16 out of 1,000 people who take ibuprofen (2,400 mg per day) or naproxen (1,000 mg per day).

ASA can also cause stomach ulcers, bleeding or other complications. There has not yet been any good-quality research on how common these side effects are when ASA is taken at higher doses. In one study, 8 out of 1,000 participants who took 1,200 mg of ASA per day developed medication-related gastric bleeding within one year.

The risk of painkiller-related stomach ulcers can be significantly reduced by taking other medication to protect the stomach. Proton pump inhibitors such as omeprazole or pantoprazole are typically used for this purpose. Medication to protect the stomach is recommended for people who are at a greater risk of gastritis, ulcers or bleeding in the gastrointestinal tract or who use NSAIDs for a longer period of time (for several weeks or long term). Most of the participants in the studies reported on here didn’t take any medication to protect their stomach.

Agency for Healthcare Research and Quality (AHRQ). Aspirin Use in Adults: Cancer, All-Cause Mortality, and Harms: A Systematic Evidence Review for the U.S. Preventive Services Task Force. September 2015 (Evidence Syntheses; Volume 132).

Coxib and traditional NSAID Trialists' (CNT) Collaboration, Bhala N, Emberson J, Merhi A, Abramson S, Arber N, Baron JA et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 2013; 382(9894): 769-779.

McGettigan P, Henry D. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies. PLoS Med 2011; 8(9): e1001098.

IQWiG health information is written with the aim of helping people understand the advantages and disadvantages of the main treatment options and health care services.

Because IQWiG is a German institute, some of the information provided here is specific to the German health care system. The suitability of any of the described options in an individual case can be determined by talking to a doctor. can provide support for talks with doctors and other medical professionals, but cannot replace them. We do not offer individual consultations.

Our information is based on the results of good-quality studies. It is written by a team of health care professionals, scientists and editors, and reviewed by external experts. You can find a detailed description of how our health information is produced and updated in our methods.

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Updated on August 10, 2017
Next planned update: 2020


Institute for Quality and Efficiency in Health Care (IQWiG, Germany)

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