Risk of Serious Atrial Fibrillation and Stroke With Use of Bisphosphonates

Sharma, Abhishek; Chatterjee, Saurav; Arbab‐Zadeh, Armin; Goyal, Sandeep; Lichstein, Edgar; Ghosh, Joydeep; Aikat, Shamik

doi:10.1378/chest.13-0675

Cited by 50 publications

(19 citation statements)

References 39 publications

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“…[ 28 , 52 ] Since these early reports,[ 23 , 24 ] several meta-analyses of RCTs and observational studies have been conducted to assess the risk of atrial fibrillation associated with bisphosphonates. Despite similarities in the included source studies, the conclusions were inconsistent: some reviews found an increase risk of serious or any atrial fibrillation,[ 26 , 27 , 30 , 34 ] whereas others did not. [ 25 , 29 , 31 – 33 ] In our meta-analysis that included the same phase 3 trials as previous meta-analyses,[ 30 , 34 ] we found that the evidence was heterogeneous and the elevated risk was mainly driven by zoledronic acid.…”

Section: Discussionmentioning

confidence: 99%

Bisphosphonates and Risk of Cardiovascular Events: A Meta-Analysis

et al. 2015

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Background and ObjectivesSome evidence suggests that bisphosphonates may reduce atherosclerosis, while concerns have been raised about atrial fibrillation. We conducted a meta-analysis to determine the effects of bisphosphonates on total adverse cardiovascular (CV) events, atrial fibrillation, myocardial infarction (MI), stroke, and CV death in adults with or at risk for low bone mass.MethodsA systematic search of MEDLINE and EMBASE through July 2014 identified 58 randomized controlled trials with longer than 6 months in duration that reported CV events. Absolute risks and the Mantel-Haenszel fixed-effects odds ratios (ORs) and 95% confidence intervals (CIs) of total CV events, atrial fibrillation, MI, stroke, and CV death were estimated. Subgroup analyses by follow-up duration, population characteristics, bisphosphonate types, and route were performed.ResultsAbsolute risks over 25–36 months in bisphosphonate-treated versus control patients were 6.5% versus 6.2% for total CV events; 1.4% versus 1.5% for atrial fibrillation; 1.0% versus 1.2% for MI; 1.6% versus 1.9% for stroke; and 1.5% versus 1.4% for CV death. Bisphosphonate treatment up to 36 months did not have any significant effects on total CV events (14 trials; ORs [95% CI]: 0.98 [0.84–1.14]; I2 = 0.0%), atrial fibrillation (41 trials; 1.08 [0.92–1.25]; I2 = 0.0%), MI (10 trials; 0.96 [0.69–1.34]; I2 = 0.0%), stroke (10 trials; 0.99 [0.82–1.19]; I2 = 5.8%), and CV death (14 trials; 0.88 [0.72–1.07]; I2 = 0.0%) with little between-study heterogeneity. The risk of atrial fibrillation appears to be modestly elevated for zoledronic acid (6 trials; 1.24 [0.96–1.61]; I2 = 0.0%), not for oral bisphosphonates (26 trials; 1.02 [0.83–1.24]; I2 = 0.0%). The CV effects did not vary by subgroups or study quality.ConclusionsBisphosphonates do not have beneficial or harmful effects on atherosclerotic CV events, but zoledronic acid may modestly increase the risk of atrial fibrillation. Given the large reduction in fractures with bisphosphonates, changes in osteoporosis treatment decision due to CV risk are not justified.

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Section: Discussionmentioning

confidence: 99%

Bisphosphonates and Risk of Cardiovascular Events: A Meta-Analysis

et al. 2015

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“…Bisphosphonate-induced hypocalcemia may affect cardiac repolarization documented by a prolonged corrected QT interval [76]. Moreover, a recent meta-analysis showed an increased risk of atrial fibrillation but no increase in the risk of stroke or cardiovascular mortality [77]. This adverse effect has not been observed in pediatric patients.…”

Section: Adverse Effects Of Bisphosphonates In Pediatric Patientsmentioning

confidence: 99%

The Use of Bisphosphonates in Pediatrics

Baroncelli

Bertelloni

2014

Horm Res Paediatr

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Bisphosphonates are widely used for the prevention and treatment of osteoporosis in adulthood. In the last years, bisphosphonates have been increasingly used in pediatric patients for the treatment of a growing number of disorders associated with osteoporosis, resistant hypercalcemia or heterotopic calcifications. The use of bisphosphonates in pediatric patients has been proven safe; however, the risk of potential severe consequences into adulthood should be kept in mind. Well-defined criteria for bisphosphonates treatment in pediatric patients are not specified, therefore an accurate selection of patients who could benefit from bisphosphonates is mandatory. A strict follow-up of pediatric patients receiving long-term bisphosphonate therapy is strongly recommended. The purpose of this mini review is to provide a summary of current knowledge on some main general aspects of the structure, mechanisms of action, pharmacokinetics, and bioavailability of bisphosphonates, and to focus on the latest advances of bisphosphonate treatment in pediatric patients. Particular attention has been paid to the common and potential adverse effects of bisphosphonate treatment, and some suggestions concerning the clinical approach and general measures for bisphosphonate treatment in pediatric patients are reported.

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“…Initial suggestion of association between bisphosphonate therapy and AF was mainly derived from serious adverse event reports (SAE) of HORIZON-PFT [2]. Later retrospective studies and meta-analyses failed to reach a consistent conclusion regarding the proposed association between bisphosphonate therapy and AF [3][4][5][6]. However, data gathered from prospective studies which directly evaluate the effects of biphosphonates on cardiac arrhythmias are still lacking.…”

Section: Discussionmentioning

confidence: 99%

“…However, many other studies and metaanalyses published after the report of the FDA reported significant association between oral and intravenous biphosphonate use and risk for development of AF [5,6].…”

Section: Introductionmentioning

confidence: 99%

Effect of intravenous zoledronic acid infusion on electrocardiographic parameters in patients with osteoporosis

et al. 2016

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ZA infusion did not affect P wave dispersion both at the immediate post-infusion period and 1 month after infusion. QT values were significantly increased early after ZA infusion; however, there were no significant differences in parameters reflecting disparity of ventricular recovery times and transmural dispersion of ventricular repolarization. Based on these observations, it may be suggested that ZA infusion did not have any short- or long-term effect on any parameter that might be associated with the tendency for atrial fibrillation or ventricular arrhythmias.

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Risk of Serious Atrial Fibrillation and Stroke With Use of Bisphosphonates

Cited by 50 publications

References 39 publications

Bisphosphonates and Risk of Cardiovascular Events: A Meta-Analysis

Bisphosphonates and Risk of Cardiovascular Events: A Meta-Analysis

The Use of Bisphosphonates in Pediatrics

Effect of intravenous zoledronic acid infusion on electrocardiographic parameters in patients with osteoporosis

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