Painkillers: How common are severe side effects of NSAIDs?

In order to better assess the risk of complications affecting the heart and blood vessels, an international group of researchers analyzed several hundred studies on treatment with commonly used NSAIDs. 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 over a period of one year. Their analysis showed that those kinds of complications occurred in 2 to 9 out of every 1,000 people who took diclofenac or ibuprofen.

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

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 up to 1,200 mg per day. This risk was still higher (but not as high) in people who took diclofenac in doses of less than 100 mg per day.

It is not known exactly after how long 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 some evidence that the risk may increase after shorter use of up to two weeks, at least in people who already have some kind of heart disease.

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

All of the NSAIDs may cause these complications. The researchers analyzed the studies to find out more about the frequency of complications affecting the gastrointestinal tract. They found 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) and
• 6 to 16 out of 1,000 people who take ibuprofen (2,400 mg per day) or naproxen (1,000 mg per day).

Acetylsalicylic acid (the drug in medicines like Aspirin) can also cause stomach ulcers, bleeding or other complications. But there's currently a lack of good-quality research on how common these side effects are when it is taken at higher doses. In one study, 8 out of 1,000 participants who took 1,200 mg of acetylsalicylic acid per day developed medication-related bleeding in the stomach 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 (PPIs) such as omeprazole or pantoprazole are typically used for this purpose. Medication to protect the stomach is recommended for people who have a greater risk of gastritis, ulcers or bleeding in the gastrointestinal tract, or those who use NSAIDs for a long period of time (over several weeks or the long term). Most of the participants in the above-mentioned studies didn’t take any medication to protect their stomach.