Oral bisphosphonates and risk of atrial fibrillation and flutter in women: a self-controlled case-series safety analysis.

<h4>Background</h4>A recent trial unexpectedly reported that atrial fibrillation, when defined as serious, occurred more often in participants randomized to an annual infusion of the relatively new parenteral bisphosphonate, zoledronic acid, than among those given placebo, but had limite...

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Main Authors: Anthony Grosso, Ian Douglas, Aroon Hingorani, Raymond MacAllister, Liam Smeeth
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0004720&type=printable
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author Anthony Grosso
Ian Douglas
Aroon Hingorani
Raymond MacAllister
Liam Smeeth
author_facet Anthony Grosso
Ian Douglas
Aroon Hingorani
Raymond MacAllister
Liam Smeeth
author_sort Anthony Grosso
collection DOAJ
description <h4>Background</h4>A recent trial unexpectedly reported that atrial fibrillation, when defined as serious, occurred more often in participants randomized to an annual infusion of the relatively new parenteral bisphosphonate, zoledronic acid, than among those given placebo, but had limited power. Two subsequent population-based case-control studies of patients receiving a more established oral bisphosphonate, alendronic acid, reported conflicting results, possibly due to uncontrolled confounding factors.<h4>Methodology/principal findings</h4>We used the United Kingdom General Practice Research Database to assess the risk of atrial fibrillation and flutter in women exposed to the oral bisphosphonates, alendronic acid and risedronate sodium. The self-controlled case-series method was used to minimise the potential for confounding. The age-adjusted incidence rate ratio for atrial fibrillation or flutter in individuals during their exposure to these oral bisphosphonates (n = 2195) was 1.07 (95% CI 0.94-1.21). The age-adjusted incidence rate ratio for alendronic acid (n = 1489) and risedronate sodium (n = 649) exposed individuals were 1.09 (95% CI 0.93-1.26) and 0.99 (95% CI 0.78-1.26) respectively. In post-hoc analyses, an increased risk of incident atrial fibrillation or flutter was detected for patients during their first few months of alendronic acid therapy.<h4>Conclusions/significance</h4>We found no robust evidence of an overall long-term increased risk of atrial fibrillation or flutter associated with continued exposure to the oral bisphosphonates, alendronic acid and risedronate sodium. A possible signal for an increase in risk during the first few months of therapy with alendronic acid needs to be re-assessed in additional studies.
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spelling doaj-art-8f3531bb9f44445b868ff7f7d0511d202025-08-20T03:22:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0143e472010.1371/journal.pone.0004720Oral bisphosphonates and risk of atrial fibrillation and flutter in women: a self-controlled case-series safety analysis.Anthony GrossoIan DouglasAroon HingoraniRaymond MacAllisterLiam Smeeth<h4>Background</h4>A recent trial unexpectedly reported that atrial fibrillation, when defined as serious, occurred more often in participants randomized to an annual infusion of the relatively new parenteral bisphosphonate, zoledronic acid, than among those given placebo, but had limited power. Two subsequent population-based case-control studies of patients receiving a more established oral bisphosphonate, alendronic acid, reported conflicting results, possibly due to uncontrolled confounding factors.<h4>Methodology/principal findings</h4>We used the United Kingdom General Practice Research Database to assess the risk of atrial fibrillation and flutter in women exposed to the oral bisphosphonates, alendronic acid and risedronate sodium. The self-controlled case-series method was used to minimise the potential for confounding. The age-adjusted incidence rate ratio for atrial fibrillation or flutter in individuals during their exposure to these oral bisphosphonates (n = 2195) was 1.07 (95% CI 0.94-1.21). The age-adjusted incidence rate ratio for alendronic acid (n = 1489) and risedronate sodium (n = 649) exposed individuals were 1.09 (95% CI 0.93-1.26) and 0.99 (95% CI 0.78-1.26) respectively. In post-hoc analyses, an increased risk of incident atrial fibrillation or flutter was detected for patients during their first few months of alendronic acid therapy.<h4>Conclusions/significance</h4>We found no robust evidence of an overall long-term increased risk of atrial fibrillation or flutter associated with continued exposure to the oral bisphosphonates, alendronic acid and risedronate sodium. A possible signal for an increase in risk during the first few months of therapy with alendronic acid needs to be re-assessed in additional studies.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0004720&type=printable
spellingShingle Anthony Grosso
Ian Douglas
Aroon Hingorani
Raymond MacAllister
Liam Smeeth
Oral bisphosphonates and risk of atrial fibrillation and flutter in women: a self-controlled case-series safety analysis.
PLoS ONE
title Oral bisphosphonates and risk of atrial fibrillation and flutter in women: a self-controlled case-series safety analysis.
title_full Oral bisphosphonates and risk of atrial fibrillation and flutter in women: a self-controlled case-series safety analysis.
title_fullStr Oral bisphosphonates and risk of atrial fibrillation and flutter in women: a self-controlled case-series safety analysis.
title_full_unstemmed Oral bisphosphonates and risk of atrial fibrillation and flutter in women: a self-controlled case-series safety analysis.
title_short Oral bisphosphonates and risk of atrial fibrillation and flutter in women: a self-controlled case-series safety analysis.
title_sort oral bisphosphonates and risk of atrial fibrillation and flutter in women a self controlled case series safety analysis
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0004720&type=printable
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