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Multicenter Study
. 2018 Aug;199:92-98.e10.
doi: 10.1016/j.jpeds.2018.03.077. Epub 2018 May 9.

Increased Fracture Risk With Furosemide Use in Children With Congenital Heart Disease

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Free PMC article
Multicenter Study

Increased Fracture Risk With Furosemide Use in Children With Congenital Heart Disease

Ji Haeng Heo et al. J Pediatr. .
Free PMC article

Abstract

Objectives: To determine the association of furosemide therapy with the incidence of bone fractures in children with congenital heart disease.

Study design: We conducted a retrospective cohort study with data extracted from the 2008-2014 Texas Medicaid databases. Pediatric patients aged <12 years diagnosed with congenital heart disease, cardiomyopathy, or heart failure were included. Patients taking furosemide were categorized into a furosemide-adherent group (medication possession ratio of ≥70%), and a furosemide-nonadherent group (medication possession ratio of <70%). A third group of patients was matched to the furosemide user groups by using propensity score matching. A multivariate logistic regression and Cox proportional hazard model with a Kaplan-Meier plot (time-to-fracture) were used to compare the 3 groups, controlling for baseline demographics and clinical characteristics.

Results: After matching, 3912 patients (furosemide adherent, n = 254; furosemide nonadherent, n = 724; no furosemide, n = 2934) were identified. The incidence of fractures was highest for the furosemide-adherent group (9.1%; 23 of 254), followed by the furosemide-nonadherent group (7.2%; 52 of 724), which were both higher than for patients who did not receive furosemide (5.0%; 148 of 2934) (P < .001). Using logistic regression, both furosemide groups were more likely to have fractures than the no furosemide group: furosemide-adherent OR of 1.9 (95% CI, 1.17-2.98; P = .009); furosemide nonadherent OR of 1.5 (95% CI, 1.10-2.14; P = .01). In the Cox proportional hazard model, the risk of fractures for the furosemide-adherent group was significantly higher compared with the no furosemide group (HR, 1.6; 95% CI, 1.00-2.42; P = .04).

Conclusions: Furosemide therapy, even with nonconsistent dosing, was associated with an increased risk of bone fractures in children with congenital heart disease.

Keywords: congenital heart disease; fractures; furosemide; loop diuretic.

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

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a Index date: the date of the first prescription claim for furosemide or a random index date within one year from the first prescription claim date b Fracture: the date of the first diagnosis claims for fractures after index date or a random index date within one year from the index date
None
a Index date: the day when patients had first claims of diuretics. b Propensity Score matching using greedy algorithm with nearest available pair matching
Figure 1.
Figure 1.
Kaplan–Meier Curve of Risk of Fractures by Furosemide Use after 3 Years Follow-up Note: Log-rank test (Furosemide-Adherent vs. Furosemide Non-adherent: Chi2=0.59, p=0.44; Furosemide-Adherent vs. No Furosemide: Chi2=5.47, p=0.02; Furosemide Non-adherent vs. No Furosemide: Chi2=4.2, p=0.04)

Comment in

  • Fractures and diuretics.
    Welch TR. Welch TR. J Pediatr. 2018 Aug;199:3. doi: 10.1016/j.jpeds.2018.06.028. J Pediatr. 2018. PMID: 30049398 No abstract available.

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