SynthesisOsteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA2012
Alendronate and atrial fibrillation: a meta-analysis of randomized placebo-controlled clinical trials.
Synthesis in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 51 citations in OpenAlex.
- Cardiovascular Safety and Effectiveness of Bisphosphonates: From Intervention Trials to Real-Life Data.Nutrients · 2022Pooled it
- Pooled it
- Fracture prediction after discontinuation of 4 to 5 years of alendronate therapy: the FLEX study.JAMA internal medicine · 2014Trial
- A disproportionality analysis of cardiac arrhythmia associated with bisphosphonates based on the FAERS database.Scientific reports · 2025Article
- Antiosteoporosis medications and cardiovascular disease: a population-based nationwide nested case-control study.Frontiers in pharmacology · 2023Article
- Cardiovascular Safety of Antifracture Medications in Patients With Osteoporosis: A Narrative Review of Evidence From Randomized Studies.JBMR plus · 2021Review
- Long-Term Bisphosphonate Therapy in Osteogenesis Imperfecta.Current osteoporosis reports · 2017Review
- Observational
- Acute effect of zoledronic acid infusion on atrial fibrillation development in patients with osteoporosis.Anatolian journal of cardiology · 2015Article
- Bisphosphonates for treatment of osteoporosis: expected benefits, potential harms, and drug holidays.Canadian family physician Medecin de famille canadien · 2014Review
- Bisphosphonate drug holiday: choosing appropriate candidates.Current osteoporosis reports · 2013Review
- Drug-induced atrial fibrillation.Drugs · 2012Review
- New understanding and treatments for osteoporosis.Endocrine · 2012Review
- Cardiovascular benefits and risks associated with calcium, vitamin D, and antiresorptive therapy in the management of skeletal fragility.Women's health (London, England)Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledIn 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.
introductionTo explore the incidence of atrial fibrillation (AF) and other cardiovascular endpoints in clinical trials of alendronate.
methodsAll 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.
resultsOf 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.
conclusionsThe 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.