NPC Archive Item: Alendronate and etidronate do not appear to increase the risk of atrial fibrillation in women.

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Sørensen HT, Christensen S, Mehnert F, et al. Use of bisphosphonates among women and risk of atrial fibrillation and flutter: population based case-control study. BMJ, 2008;336:813-6

May 14th 2008

This cohort study of a large Danish population found no evidence that the oral bisphosphonates alendronate and etidronate increase the risk of atrial fibrillation (AF) in women.

What is the background to this?
NICE recommends oral bisphosphonates (alendronate, etidronate and risedronate) as treatment options for the secondary prevention of osteoporotic fragility fractures (see Technology Appraisal Guidance 87 for more details). Zoledronic acid▼, by yearly intravenous infusion, may be considered where oral bisphosphonates can not be tolerated (see NPC Stop Press blog 18 and Rapid Review blog 12).

There is some inconclusive evidence that bisphosphonates, and in particular zoledronic acid, are associated with an increased risk of AF (see Editorial). This study provides further information with which to assess the significance of any association between oral bisphosphonates and the development of AF.

What does this study claim?
There was no evidence that alendronate and etidronate increase the risk of AF and flutter in women.

So what?
Although the conclusions of this study are limited by its observational and retrospective nature, it provides some reassurance that the use of alendronate and etidronate is unlikely to increase the risk of AF in women. However, the study provides no additional information regarding the risk of AF with risedronate (only used by 5 control patients in the study) and zoledronic acid (not used).

Prescribers are advised to continue to follow NICE guidance with regard to the use of oral bisphosphonates for secondary prevention of fractures in postmenopausal women with osteoporosis. This guideline is currently being reviewed by NICE and we will inform readers once it is updated

Study details
This was a retrospective case-control study using medical databases from Denmark. Patients admitted to hospital with a first diagnosis of AF or flutter between 1999 and 2005 were identified from the database. Based on the results of a previous study, which found that 5% of patients had atrial flutter, the majority of patients in  this cohort were likely to have AF. Each case was matched with five population controls, based on age, sex, and county. There was no significant difference in the risk of AF or flutter between patients who were using bisphosphonates (alendronate and etidronate) (435 of 13,586; 3.2%) compared with population controls (non-users) (1,958 of 68,054; 2.9%).  Both drugs were used at about the same frequency in cases and controls. The adjusted relative risk (RR) of current users compared with non-users was 0.95 (95%CI 0.84 to 1.07). There were also no significant differences in the RRs in both new and continuing user subgroups, or in patients who had received 1–3, 4–9, or >10 prescriptions for bisphosphonates from 1997 up to the date of diagnosis.

This review was funded by the Western Danish Research Forum for Health Sciences.

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