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Correspondence |

Bisphosphonates and Atrial Fibrillation in Elderly Men: Casual or Causal Association? FREE TO VIEW

Yashasvi Chugh, MD; Robert T. Faillace, MD
Author and Funding Information

FINANCIAL/NONFINANCIAL DISCLOSURES: None declared.

aJacobi Medical Center/Albert Einstein College of Medicine, Bronx, NY

bNorth Bronx Healthcare Network (Jacobi Medical Center and North Central Bronx Hospital), Bronx, NY

CORRESPONDENCE TO: Yashasvi Chugh, MD, 1400 Pelham Pkwy S, Jacobi Medical Center/Albert Einstein College of Medicine, Bronx, NY 10461


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;150(3):755-756. doi:10.1016/j.chest.2016.06.044
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We would like to congratulate Thadani et al for their recent report in CHEST (May 2016) that attempted to expand on an unstudied cause and effect model for the occurrence of atrial fibrillation (AF) in men undergoing bisphosphonate therapy. This subanalysis found that bisphosphonate use in elderly men was associated with a greater OR of prevalent nocturnal AF when examined by using a multivariable adjusted model but not clinically relevant incident AF. However, there are a few concerning methodologic deficiencies that may have misguided the conclusion.

The data of self-reported AF/atrial flutter that were obtained by investigators were not stratified as paroxysmal, persistent, or permanent. The interpretation of prevalent nocturnal AF (nocturnal polysomnography) may have been much higher if either of the two arms of the study had a greater number of patients with persistent or permanent AF. In addition, information was not provided on how many patients with prevalent nocturnal AF had been diagnosed with or self-reported AF/atrial flutter prior to starting bisphosphonate therapy.

After a multivariable analysis, prevalent nocturnal AF was noted to be significantly greater in “current bisphosphonate users” (Table 2). There were 127 cases of prevalent nocturnal AF in 2756 nonusers (vs 10 of 121 cases in users); however, it is unclear how many patients actually had a history of self-reported AF. Also lacking was a multivariable adjusted analysis conducted after removing patients with a history of self-reported AF from the group who had nocturnal AF.

The data regarding clinically relevant incident AF did not reach statistical significance when patients with a history of self-reported AF were removed from the adjusted analysis. This outcome further points toward a possible confounder in the conclusion gathered regarding prevalent nocturnal AF. One can only speculate, based on the available data, whether the prevalent nocturnal AF in bisphosphonate users was truly a result of medication use or a confounder.

A recent meta-analysis reported the absence of a correlation between bisphosphonate use and AF but found a modestly elevated risk in trials involving the use of zoledronic acid (pooled OR, 1.24 [95% CI, 0.96-1.61]). Furthermore, in a trial of zoledronic acid (Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly-Pivotal Fracture Trial [HORIZON-PFT]), users had an increased incidence of AF that led to hospitalizations, but overall AF incidence was similar to nonusers. Thus, it may be interesting to know what type of bisphosphonate was used by patients in the current subanalysis by Thadani et al.

The mechanism and clinical relevance of AF in elderly male bisphosphonate users remain unclear and may form the basis of well-powered trials in the future.

References

Thadani S.R. .Ristow B. .Blackwell T. .et al Relationship of bisphosphonate therapy and atrial fibrillation/flutter: Outcomes of Sleep Disorders in Older Men (MrOS Sleep) study. Chest. 2016;149:1173-1180 [PubMed]journal. [CrossRef] [PubMed]
 
Kim D.H. .Rogers J.R. .Fulchino L.A. .Kim C.A. .Solomon D.H. .Kim S.C. . Bisphosphonates and risk of cardiovascular events: a meta-analysis. PLoS One. 2015;10:1-13 [PubMed]journal
 
Black D.M. .Delmas P.D. .Eastell R. .et al Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356:1809-1822 [PubMed]journal. [CrossRef] [PubMed]
 

Figures

Tables

References

Thadani S.R. .Ristow B. .Blackwell T. .et al Relationship of bisphosphonate therapy and atrial fibrillation/flutter: Outcomes of Sleep Disorders in Older Men (MrOS Sleep) study. Chest. 2016;149:1173-1180 [PubMed]journal. [CrossRef] [PubMed]
 
Kim D.H. .Rogers J.R. .Fulchino L.A. .Kim C.A. .Solomon D.H. .Kim S.C. . Bisphosphonates and risk of cardiovascular events: a meta-analysis. PLoS One. 2015;10:1-13 [PubMed]journal
 
Black D.M. .Delmas P.D. .Eastell R. .et al Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356:1809-1822 [PubMed]journal. [CrossRef] [PubMed]
 
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