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Bisphosphonates and risk of cardiovascular events: a meta-analysis.

Kim DH, Rogers JR, Fulchino LA, Kim CA, Solomon DH, Kim SC - PLoS ONE (2015)

Bottom Line: Subgroup analyses by follow-up duration, population characteristics, bisphosphonate types, and route were performed.The CV effects did not vary by subgroups or study quality.Given the large reduction in fractures with bisphosphonates, changes in osteoporosis treatment decision due to CV risk are not justified.

View Article: PubMed Central - PubMed

Affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America; Division of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.

ABSTRACT

Background and objectives: Some 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.

Methods: A 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.

Results: Absolute 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.

Conclusions: Bisphosphonates 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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Related in: MedlinePlus

Meta-Analysis of Myocardial Infarction and Stroke with Use of Bisphosphonates.* Abbreviations: CI, confidence interval; HORIZON-PFT, the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial; HORIZON-RFT, the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Recurrent Fracture Trial; M-H, Mantel Haenszel; OR, odds ratio. * Karam (2007) et al. included data from 6 trials of risedronate. Individual study data were not available.
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pone.0122646.g004: Meta-Analysis of Myocardial Infarction and Stroke with Use of Bisphosphonates.* Abbreviations: CI, confidence interval; HORIZON-PFT, the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial; HORIZON-RFT, the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Recurrent Fracture Trial; M-H, Mantel Haenszel; OR, odds ratio. * Karam (2007) et al. included data from 6 trials of risedronate. Individual study data were not available.

Mentions: The risks of MI, stroke, and CV death over 25–36 months in bisphosphonate-treated patients and control patients were low (MI: 1.0% versus 1.2%; stroke: 1.6% versus 1.9%; and CV death: 1.5% versus 1.4%) and similar between the treated and placebo patients (Figs 4 and 5). There was no statistically significant difference in the pooled ORs across the pre-defined subgroups (Figs 4, 5, and 6 in S1 File).


Bisphosphonates and risk of cardiovascular events: a meta-analysis.

Kim DH, Rogers JR, Fulchino LA, Kim CA, Solomon DH, Kim SC - PLoS ONE (2015)

Meta-Analysis of Myocardial Infarction and Stroke with Use of Bisphosphonates.* Abbreviations: CI, confidence interval; HORIZON-PFT, the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial; HORIZON-RFT, the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Recurrent Fracture Trial; M-H, Mantel Haenszel; OR, odds ratio. * Karam (2007) et al. included data from 6 trials of risedronate. Individual study data were not available.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4401508&req=5

pone.0122646.g004: Meta-Analysis of Myocardial Infarction and Stroke with Use of Bisphosphonates.* Abbreviations: CI, confidence interval; HORIZON-PFT, the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial; HORIZON-RFT, the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Recurrent Fracture Trial; M-H, Mantel Haenszel; OR, odds ratio. * Karam (2007) et al. included data from 6 trials of risedronate. Individual study data were not available.
Mentions: The risks of MI, stroke, and CV death over 25–36 months in bisphosphonate-treated patients and control patients were low (MI: 1.0% versus 1.2%; stroke: 1.6% versus 1.9%; and CV death: 1.5% versus 1.4%) and similar between the treated and placebo patients (Figs 4 and 5). There was no statistically significant difference in the pooled ORs across the pre-defined subgroups (Figs 4, 5, and 6 in S1 File).

Bottom Line: Subgroup analyses by follow-up duration, population characteristics, bisphosphonate types, and route were performed.The CV effects did not vary by subgroups or study quality.Given the large reduction in fractures with bisphosphonates, changes in osteoporosis treatment decision due to CV risk are not justified.

View Article: PubMed Central - PubMed

Affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America; Division of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.

ABSTRACT

Background and objectives: Some 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.

Methods: A 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.

Results: Absolute 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.

Conclusions: Bisphosphonates 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.

Show MeSH
Related in: MedlinePlus