ABSTRACT & COMMENTARY
Risk of Developing Atrial Fibrillation with Use of Bisphosphonates
By Harold L. Karpman, MD, FACC, FACP
Clinical Professor of Medicine, UCLA School of Medicine
Dr. Karpman reports no financial relationships relevant to this field of study.
The risk of developing atrial fibrillation is increased by the use of oral or intravenous bisphosphonates, but the risk is relatively greater when the drug is given intravenously.
Sharma A, et al. Risk of atrial fibrillation with use of oral and intravenous bisphosphonates. Am J Cardiol 2014;113:1815-1821.
Bisphosphonates are usually used as the first-line therapy for the treatment of osteoporosis and osteopenia because they effectively reduce the risk of osteoporotic fractures.1 However, recent studies using both the oral and intravenous forms have reported an increased risk of occurrence of atrial fibrillation.2-9 Because of uncertainty as to whether the intravenous form of bisphosphonate carried a greater risk, Sharma and colleagues performed a systematic review and meta-analysis of the literature from 1966-2013.10
The nine studies (135,347 participants) included in the final analysis revealed a statistically significant increased risk of new-onset atrial fibrillation occurring when administering bisphosphonates either intravenously or orally. Moreover, the data suggested that the risk was significantly greater when the drug was used intravenously although the absolute risk remains low (1.1% and 0.4% for intravenous and oral bisphosphonates, respectively).
COMMENTARY
The potential pathophysiological mechanisms underlying the apparent association between bisphosphonate administration and the development of atrial fibrillation are not well understood and remain speculative. Alteration of numerous biochemical factors and an increase in a pro-inflammatory state could all be contributing factors. Although the results clearly suggest an association between new-onset atrial fibrillation and bisphosphonate use, causality could not be definitely established because detailed data were lacking on associated cardiovascular risk factors such as dyslipidemia, smoking, alcohol consumption, obesity, and concomitant medication use. Obviously, prospective randomized data will be needed to further evaluate the risk of atrial fibrillation with bisphosphonate therapy and to determine whether the association is a "class" effect or is dependent on the specific drug utilized, route of administration of the drug, age of the patient, and/or the presence or absence of one or more of the multiple cardiovascular risk factors.
REFERENCES
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- Cummings SR, et al. Alendronate and atrial fibrillation. N Engl J Med 2007;356:1895-1896.
- Abrahamsen B, et al. Atrial fibrillation in fracture patients treated with oral bisphosphonates.
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- Sharma A, et al. Risk of serious atrial fibrillation and stroke with use of bisphosphonates: Evidence from a meta-analysis. Chest 2013;144:1311-1322.
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- Loke YK, et al. Bisphosphonates and atrial fibrillation: Systematic review and meta-analysis. Drug Saf 2009;32:219-228.
- Sharma A, et al. Risk of atrial fibrillation with use of oral and intravenous bisphosphonates. Am J Cardiol 2014;113:1815-1821.
