Bisphosphonates increase risk of serious atrial fibrillation by a small amount

Sharma A, Chatterjee S, Arbab-Zadeh A, et al. Risk of serious atrial fibrillation and stroke with use of bisphosphonates: evidence from a meta-analysis. Chest. 2013;144:1311-22.

Review question

Are bisphosphonates associated with serious atrial fibrillation, stroke, or cardiovascular death?

Background

Osteoporosis is a condition that causes the bones to become weak or brittle and more likely to break if a person falls. Older people and women who have reached menopause are at greater risk of osteoporosis. Bisphosphonates are a type of drug used to increase bone strength and prevent bone fractures (or breaks) in people with osteoporosis. There is some concern that bisphosphonates may increase the risk of atrial fibrillation, stroke, or death due to cardiovascular causes.

How the review was done

The researchers did a systematic review, searching for studies published up to April 2012. They found 12 studies, including 6 randomized controlled trials with 41,375 people (average age 67 to 75 years).

Key features of the 6 randomized controlled trials were:

• people were men or postmenopausal women with osteoporosis, or men and women 50 years or older who had surgery for hip fracture;
• bisphosphonates included zoledronic acid (Reclast®, Zometa®), alendronate (Fosamax®), risedronate (Actonel®, Atelvia®), and ibandronate (Boniva®), and were taken by mouth (pills) or intravenously (by needle into a vein); and
• bisphosphonates were compared with placebo in 5 trials and with a low-dose bisphosphonate (ibandronate) in 1 trial.

What the researchers found

All 6 randomized trials were rated as good quality.

Compared with placebo or low-dose ibandronate, bisphosphonates:

• increased serious atrial fibrillation by about 0.13% (from 0.66% to 0.79%)
• did not increase risk of stroke; and
• did not increase risk of death due to cardiovascular causes.

Conclusions

Bisphosphonates increase risk of serious atrial fibrillation by a small amount. They do not increase risks of stroke or death due to cardiovascular causes.

Bisphosphonates vs placebo or low-dose ibandronate*

*Based on results from randomized controlled trials only.

†Although the rates for the 2 groups look a little different, the differences were not statistically significant. This means that the differences could simply be due to chance rather than due to the different treatments.