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Heart failure in patients treated with bisphosphonates
Author(s) -
Grove E. L.,
Abrahamsen B.,
Vestergaard P.
Publication year - 2013
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/joim.12087
Subject(s) - medicine , heart failure , hazard ratio , raloxifene , confidence interval , proportional hazards model , etidronic acid , relative risk , bisphosphonate , population , osteoporosis , cohort study , cardiology , surgery , cancer , breast cancer , environmental health , estrogen receptor
Objectives The aim of this study was to investigate the occurrence of heart failure in patients treated with bisphosphonates. Design In this nationwide retrospective cohort study from D enmark, all users of bisphosphonates and raloxifene between 1996 and 2006 ( n = 102 342) were included in the ‘exposed’ group and three age‐ and gender‐matched subjects ( n = 307.026) from the general population comprised the control group. The risk of heart failure was estimated by C ox proportional hazard analyses. Results The mean follow‐up times were 2.8, 5.5 and 4.9 years for alendronate‐, etidronate‐ and raloxifene‐treated patients, respectively. The absolute risk of heart failure was 4.4% in the exposed group and 3.7% in the control group ( P < 0.01). The relative risk ( RR ) of heart failure was significantly increased in users of bisphophonates: crude RR 1.71 [95% confidence interval ( CI ) 1.63–1.79]; adjusted hazard ratio ( HR ) 1.41 (95% CI 1.34–1.48). By comparison, raloxifene, which is used for the same indication but has a different mechanism of action, was not associated with an increased risk of heart failure: adjusted HR 1.07 (95% CI 0.76–1.50). When the two most commonly used bisphosphonates, alendronate and etidronate, were analysed separately, significant trends in the risk of heart failure were observed across refill compliance strata. The risk of heart failure increased significantly with increasing refill compliance for etidronate ( P for trend <0.01), whereas it decreased for alendronate ( P for trend <0.01). Conclusions Bisphosphonate users were at increased risk of heart failure compared to age‐ and gender‐matched control subjects. However, users of alendronate showed a dose‐dependent reduction in this risk, suggesting that alendronate may reduce the risk of heart failure.