TY - JOUR
T1 - Prevalent digoxin use and subsequent risk of death or hospitalization in ambulatory heart failure patients with a reduced ejection fraction—Findings from the Heart Failure
T2 - A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) randomized controlled trial
AU - Ambrosy, Andrew P.
AU - Bhatt, Ankeet S.
AU - Stebbins, Amanda L.
AU - Wruck, Lisa M.
AU - Fudim, Marat
AU - Greene, Stephen J.
AU - Kraus, William E.
AU - O'Connor, Christopher M.
AU - Piña, Ileana L.
AU - Whellan, David J.
AU - Mentz, Robert J.
N1 - Funding Information:
The HF-ACTION trial was funded via grant support provided by the National Heart, Lung, and Blood Institute ( ClinicalTrials.gov Number: NCT00047437 ). Database management and statistical analysis was performed by the Duke Clinical Research Institute. The authors take responsibility for the manuscript's integrity and had complete control and authority over its preparation and the decision to publish.
Funding Information:
Conflict of Interest: CMO reports consulting fees from Novella and Amgen; ownership/partnership/principal in Biscardia, LLC; and research support from Otsuka, Roche Diagnostics, BG Medicine, Critical Diagnostics, Astellas, Gilead, GE Healthcare, and ResMed. RJM receives research support from Amgen, AstraZeneca, BMS, GSK, Gilead, Novartis, Otsuka, and ResMed; and honoraria from Thoratec. All other authors declare no relevant financial disclosures.
Publisher Copyright:
© 2018
PY - 2018/5
Y1 - 2018/5
N2 - Background: Despite more than 200 years of clinical experience and a pivotal trial, recently published research has called into question the safety and efficacy of digoxin therapy in heart failure (HF). Methods: HF-ACTION (ClinicalTrials.gov Number: NCT00047437) enrolled 2331 outpatients with HF and an EF ≤35% between April 2003 and February 2007 and randomized them to aerobic exercise training versus usual care. Patients were grouped according to prevalent digoxin status at baseline. The association between digoxin therapy and outcomes was assessed using Cox proportional hazard and inverse-probability weighted (IPW) regression models adjusted for demographics, medical history, medications, laboratory values, quality of life, and exercise parameters. Results: The prevalence of digoxin therapy decreased from 52% during the first 6 months of enrollment to 35% at the end of the HF-ACTION trial (P <0.0001). Study participants were 59± 13 years of age, 72% were male, and approximately half had an ischemic etiology of HF. Patients receiving digoxin at baseline tended to be younger and were more likely to report New York Heart Association functional class III/IV symptoms (rather than class II) compared to those not receiving digoxin. Patients taking digoxin had worse baseline exercise capacity as measured by peak VO 2 and 6-min walk test and greater impairments in health status as reflected by the Kansas City Cardiomyopathy Questionnaire. The association between digoxin and the risk of death or hospitalization differed depending on whether Cox proportional hazard (Hazard Ratio 1.03, 95% Confidence Interval 0.92–1.16; P =.62) or IPW regression models (HR 1.08, 95% CI 1.00–1.17; P =.057) were used to adjust for potential confounders. Conclusion: Although digoxin use was associated with high-risk clinical features, the association between digoxin therapy and outcomes was dependent on the statistical methods used for multivariable adjustment. Clinical equipoise exists and additional prospective research is required to clarify the role of digoxin in contemporary clinical practice including its effects on functional capacity, quality of life, and long-term outcomes.
AB - Background: Despite more than 200 years of clinical experience and a pivotal trial, recently published research has called into question the safety and efficacy of digoxin therapy in heart failure (HF). Methods: HF-ACTION (ClinicalTrials.gov Number: NCT00047437) enrolled 2331 outpatients with HF and an EF ≤35% between April 2003 and February 2007 and randomized them to aerobic exercise training versus usual care. Patients were grouped according to prevalent digoxin status at baseline. The association between digoxin therapy and outcomes was assessed using Cox proportional hazard and inverse-probability weighted (IPW) regression models adjusted for demographics, medical history, medications, laboratory values, quality of life, and exercise parameters. Results: The prevalence of digoxin therapy decreased from 52% during the first 6 months of enrollment to 35% at the end of the HF-ACTION trial (P <0.0001). Study participants were 59± 13 years of age, 72% were male, and approximately half had an ischemic etiology of HF. Patients receiving digoxin at baseline tended to be younger and were more likely to report New York Heart Association functional class III/IV symptoms (rather than class II) compared to those not receiving digoxin. Patients taking digoxin had worse baseline exercise capacity as measured by peak VO 2 and 6-min walk test and greater impairments in health status as reflected by the Kansas City Cardiomyopathy Questionnaire. The association between digoxin and the risk of death or hospitalization differed depending on whether Cox proportional hazard (Hazard Ratio 1.03, 95% Confidence Interval 0.92–1.16; P =.62) or IPW regression models (HR 1.08, 95% CI 1.00–1.17; P =.057) were used to adjust for potential confounders. Conclusion: Although digoxin use was associated with high-risk clinical features, the association between digoxin therapy and outcomes was dependent on the statistical methods used for multivariable adjustment. Clinical equipoise exists and additional prospective research is required to clarify the role of digoxin in contemporary clinical practice including its effects on functional capacity, quality of life, and long-term outcomes.
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U2 - 10.1016/j.ahj.2018.02.004
DO - 10.1016/j.ahj.2018.02.004
M3 - Article
C2 - 29754673
AN - SCOPUS:85042851068
VL - 199
SP - 97
EP - 104
JO - American Heart Journal
JF - American Heart Journal
SN - 0002-8703
ER -