Cargando…
Alendronate and atrial fibrillation: a meta-analysis of randomized placebo-controlled clinical trials
SUMMARY: In this meta-analysis of all Merck-conducted, placebo-controlled clinical trials of alendronate, the occurrence of AF was uncommon, with most studies reporting two or fewer events. Across all studies, no clear association between overall bisphosphonate exposure and the rate of serious or no...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer-Verlag
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249176/ https://www.ncbi.nlm.nih.gov/pubmed/21369791 http://dx.doi.org/10.1007/s00198-011-1546-9 |
_version_ | 1782220303956443136 |
---|---|
author | Barrett-Connor, E. Swern, A. S. Hustad, C. M. Bone, H. G. Liberman, U. A. Papapoulos, S. Wang, H. de Papp, A. Santora, A. C. |
author_facet | Barrett-Connor, E. Swern, A. S. Hustad, C. M. Bone, H. G. Liberman, U. A. Papapoulos, S. Wang, H. de Papp, A. Santora, A. C. |
author_sort | Barrett-Connor, E. |
collection | PubMed |
description | SUMMARY: In this meta-analysis of all Merck-conducted, placebo-controlled clinical trials of alendronate, the occurrence of AF was uncommon, with most studies reporting two or fewer events. Across all studies, no clear association between overall bisphosphonate exposure and the rate of serious or non-serious AF was observed. INTRODUCTION: To explore the incidence of atrial fibrillation (AF) and other cardiovascular endpoints in clinical trials of alendronate. METHODS: All double-blind, placebo-controlled studies of alendronate 5, 10, or 20 mg daily, 35 mg once-weekly, 35 mg twice-weekly, and 70 mg once-weekly of at least 3 months duration conducted by Merck were included in this meta-analysis. The primary method of analysis was exact Poisson regression. Estimated relative risk (RR) of alendronate versus placebo and the associated 95% confidence interval was derived from a model that included number of episodes with factors for treatment group and study and an offset parameter for number of person-years on study. RESULTS: Of 41 studies considered, 32 met all criteria for inclusion in the analysis (participants—9,518 alendronate, 7,773 placebo). Estimated RR for all AF events was 1.16 (95% CI = 0.87, 1.55; p = 0.33). Most trials had two or fewer AF events. The RR of AF classified as a serious adverse event was 1.25 (95% CI = 0.82, 1.93; p = 0.33), but became 0.97 (95% CI = 0.51, 1.85) when the clinical fracture cohort of the Fracture Intervention Trial was excluded, indicating that results were driven by events in that study. Estimated RRs for other cardiovascular endpoints were less than 1. CONCLUSIONS: The incidence of atrial fibrillation was low in Merck clinical trials of alendronate and was not significantly increased in any single trial nor in the meta-analysis. Based on this analysis, alendronate use does not appear to be associated with an increased risk of atrial fibrillation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00198-011-1546-9) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-3249176 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Springer-Verlag |
record_format | MEDLINE/PubMed |
spelling | pubmed-32491762012-01-11 Alendronate and atrial fibrillation: a meta-analysis of randomized placebo-controlled clinical trials Barrett-Connor, E. Swern, A. S. Hustad, C. M. Bone, H. G. Liberman, U. A. Papapoulos, S. Wang, H. de Papp, A. Santora, A. C. Osteoporos Int Original Article SUMMARY: In this meta-analysis of all Merck-conducted, placebo-controlled clinical trials of alendronate, the occurrence of AF was uncommon, with most studies reporting two or fewer events. Across all studies, no clear association between overall bisphosphonate exposure and the rate of serious or non-serious AF was observed. INTRODUCTION: To explore the incidence of atrial fibrillation (AF) and other cardiovascular endpoints in clinical trials of alendronate. METHODS: All double-blind, placebo-controlled studies of alendronate 5, 10, or 20 mg daily, 35 mg once-weekly, 35 mg twice-weekly, and 70 mg once-weekly of at least 3 months duration conducted by Merck were included in this meta-analysis. The primary method of analysis was exact Poisson regression. Estimated relative risk (RR) of alendronate versus placebo and the associated 95% confidence interval was derived from a model that included number of episodes with factors for treatment group and study and an offset parameter for number of person-years on study. RESULTS: Of 41 studies considered, 32 met all criteria for inclusion in the analysis (participants—9,518 alendronate, 7,773 placebo). Estimated RR for all AF events was 1.16 (95% CI = 0.87, 1.55; p = 0.33). Most trials had two or fewer AF events. The RR of AF classified as a serious adverse event was 1.25 (95% CI = 0.82, 1.93; p = 0.33), but became 0.97 (95% CI = 0.51, 1.85) when the clinical fracture cohort of the Fracture Intervention Trial was excluded, indicating that results were driven by events in that study. Estimated RRs for other cardiovascular endpoints were less than 1. CONCLUSIONS: The incidence of atrial fibrillation was low in Merck clinical trials of alendronate and was not significantly increased in any single trial nor in the meta-analysis. Based on this analysis, alendronate use does not appear to be associated with an increased risk of atrial fibrillation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00198-011-1546-9) contains supplementary material, which is available to authorized users. Springer-Verlag 2011-03-03 2012 /pmc/articles/PMC3249176/ /pubmed/21369791 http://dx.doi.org/10.1007/s00198-011-1546-9 Text en © The Author(s) 2011 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. |
spellingShingle | Original Article Barrett-Connor, E. Swern, A. S. Hustad, C. M. Bone, H. G. Liberman, U. A. Papapoulos, S. Wang, H. de Papp, A. Santora, A. C. Alendronate and atrial fibrillation: a meta-analysis of randomized placebo-controlled clinical trials |
title | Alendronate and atrial fibrillation: a meta-analysis of randomized placebo-controlled clinical trials |
title_full | Alendronate and atrial fibrillation: a meta-analysis of randomized placebo-controlled clinical trials |
title_fullStr | Alendronate and atrial fibrillation: a meta-analysis of randomized placebo-controlled clinical trials |
title_full_unstemmed | Alendronate and atrial fibrillation: a meta-analysis of randomized placebo-controlled clinical trials |
title_short | Alendronate and atrial fibrillation: a meta-analysis of randomized placebo-controlled clinical trials |
title_sort | alendronate and atrial fibrillation: a meta-analysis of randomized placebo-controlled clinical trials |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249176/ https://www.ncbi.nlm.nih.gov/pubmed/21369791 http://dx.doi.org/10.1007/s00198-011-1546-9 |
work_keys_str_mv | AT barrettconnore alendronateandatrialfibrillationametaanalysisofrandomizedplacebocontrolledclinicaltrials AT swernas alendronateandatrialfibrillationametaanalysisofrandomizedplacebocontrolledclinicaltrials AT hustadcm alendronateandatrialfibrillationametaanalysisofrandomizedplacebocontrolledclinicaltrials AT bonehg alendronateandatrialfibrillationametaanalysisofrandomizedplacebocontrolledclinicaltrials AT libermanua alendronateandatrialfibrillationametaanalysisofrandomizedplacebocontrolledclinicaltrials AT papapouloss alendronateandatrialfibrillationametaanalysisofrandomizedplacebocontrolledclinicaltrials AT wangh alendronateandatrialfibrillationametaanalysisofrandomizedplacebocontrolledclinicaltrials AT depappa alendronateandatrialfibrillationametaanalysisofrandomizedplacebocontrolledclinicaltrials AT santoraac alendronateandatrialfibrillationametaanalysisofrandomizedplacebocontrolledclinicaltrials |