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)?

Background

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.

Conclusions

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