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NSAIDS, except naproxen, increase major coronary events; all NSAIDs increase heart failure and upper gastrointestinal complications

Bhala N, Emberson J, Merhi A, et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013;382:769-79.

Review question

What are the vascular and gastrointestinal effects of non-steroidal anti-inflammatory drugs (NSAIDs)?


NSAIDs reduce pain, fever, and inflammation. Traditional NSAIDs include aspirin, ibuprofen, and naproxen.

Selective COX-2 inhibitors (coxibs) are a newer type of NSAID that target the COX-2 inflammatory protein.

The long-term use of NSAIDs is limited by serious gastrointestinal (GI) side effects.

How the review was done

This summary is based on a meta-analysis of 754 randomized controlled trials that included 353,809 people. 280 trials (124,513 people) compared NSAIDs with placebo, and 474 trials (229,296 people) compared 2 different NSAIDs. The publication period was 1990 to 2011.

In studies providing individual participant data, the average age at start of treatment was 61 years.

NSAIDs included were coxibs, diclofenac, ibuprofen, and naproxen.

Outcomes included major vascular events (non-fatal heart attack, non-fatal stroke, or vascular death); major coronary events (non-fatal heart attack or heart problems); heart failure; and gastrointestinal complications (perforation, obstruction, or bleed).

What the researchers found

As shown in the Table below, compared with placebo,

  • coxibs and diclofenac increased major vascular events, major coronary events, and vascular death. For 1,000 people prescribed a coxib or diclofenac for 1 year, 3 more had major vascular events, 1 of which was fatal.
  • ibuprofen increased coronary events.
  • all NSAIDS roughly doubled the risk of heart failure. For 1000 people taking coxibs for 1 year, 4 more had heart failure.
  • all NSAIDS increased GI complications. For 1000 people taking coxibs for 1 year, 3 more had GI complications.


Non-steroidal anti-inflammatory drugs (NSAIDs), except for naproxen, increase major coronary events.

All NSAIDs increase heart failure and upper gastrointestinal complications more than placebo. The absolute increase in risk is small, but the complications can be serious.

Relative increase with NSAIDs compared with placebo or no treatment


Vascular events

Coronary events

Heart failure

Vascular death

GI complications


37% increase

76% increase

128% increase

58% increase

81% increase


41% increase

70% increase

85% increase

65% increase

89% increase


No increase

122% increase

149% increase

No increase

97% increase


No increase

No increase

87% increase

No increase

322% increase



Coronary events
Adverse events caused by conditions affecting the coronary arteries that supply oxygen and blood to the heart.
Related to the stomach and the intestines (bowels).
Major coronary events
Adverse events from conditions affecting the coronary arteries that supply oxygen and blood to the heart.
Advanced statistical methods contrasting and combining results from different studies.
A harmless, inactive, and simulated treatment.
Randomized controlled trials
Studies where people are assigned to one of the treatments purely by chance.
The body's network of blood vessels. It includes the arteries, veins, and capillaries that carry blood to and from the heart.
Vascular death
Death from circulatory problems.

Related Web Resources

  • Coronary artery disease risk screening

    Health Link B.C.
    Men over 40 and women past menopause or over 50 should get screened for coronary artery disease (CAD) every 1 to 3 years. Your risk is higher if you have diabetes, high blood pressure, abdominal obesity, kidney disease, family history of CAD or if you smoke.
  • High cholesterol: Does reducing the amount of fat in your diet help?

    Informed Health Online
    Eat less saturated fats in your diet to help prevent heart disease. Eat less meat, butter, cheese and cream to improve your health long-term.
  • Statins: Should I Take Them to Prevent a Heart Attack or Stroke?

    This patient decision aid helps people considering taking medicines called statins to lower their risk of heart attack and stroke by comparing the benefits, risks, and side effects of both options. It also includes alternative treatment options to taking statins such as trying to lower risk with lifestyle changes.
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