Risk of atrial fibrillation among bisphosphonate users: a multicenter, population-based, Italian study.
Bisphosphonate treatment is used to prevent bone fractures. A controversial association of bisphosphonate use and risk of atrial fibrillation has been reported. In our study, current alendronate users were associated with a higher risk of atrial fibrillation as compared with those who had stopped bisphosphonate (BP) therapy for more than 1 year.


BACKGROUND
Bisphosphonates are widely used to prevent bone fractures. Controversial findings regarding the association between bisphosphonate use and the risk of atrial fibrillation (AF) have been reported. The aim of this study was to evaluate the risk of AF in association with BP exposure.


METHODS
We performed a nested case-control study using the databases of drug-dispensing and hospital discharge diagnoses from five Italian regions. The data cover a period ranging from July 1, 2003 to December 31, 2006. The study population comprised new users of bisphosphonates aged 55 years and older. Patients were followed from the first BP prescription until an occurrence of an AF diagnosis (index date, i.e., ID), cancer, death, or the end of the study period, whichever came first. For the risk estimation, any AF case was matched by age and sex to up to 10 controls from the same source population. A conditional logistic regression was performed to obtain the odds ratio with 95% confidence intervals (CI). The BP exposure was classified into current (<90 days prior to ID), recent (91-180), past (181-364), and distant past (≥365) use, with the latter category being used as a reference point. A subgroup analysis by individual BP was then carried out.


RESULTS
In comparison with distant past users of BP, current users of BP showed an almost twofold increased risk of AF: odds ratio (OR) = 1.78 and 95% CI = 1.46-2.16. Specifically, alendronate users were mostly associated with AF as compared with distant past use of BP (OR, 1.97; 95% CI, 1.59-2.43).


CONCLUSIONS
In our nested case-control study, current users of BP are associated with a higher risk of atrial fibrillation as compared with those who had stopped BP treatment for more than 1 year.
Department of Internal Medicine, Erasmus Medical Center University, Rotterdam, Netherlands.
L
L
Herrera
I
I
Leal
F
F
Lapi
M
M
Schuemie
V
V
Arcoraci
F
F
Cipriani
E
E
Sessa
A
A
Vaccheri
C
C
Piccinni
T
T
Staniscia
A
A
Vestri
M
M
Di Bari
G
G
Corrao
A
A
Zambon
D
D
Gregori
F
F
Carle
M
M
Sturkenboom
G
G
Mazzaglia
G
G
Trifiro
D000284:Administration, Oral; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000139:chemically induced* / Q000453:epidemiology; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects*; D016022:Case-Control Studies; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment / Q000379:methods; D017678:Sex Distribution
D050071:Bone Density Conservation Agents; D004164:Diphosphonates