• Jenica N Upshaw, David van Klaveren, Marvin A Konstam, and David M Kent.
• The CardioVascular Center, Tufts Medical Center, Boston, Mass. Electronic address: jupshaw@tuftsmedicalcenter.org.
• Am. J. Med. 2018 Jun 1; 131 (6): 676-683.e2.

BackgroundDigoxin has been shown to reduce heart failure hospitalizations with a neutral effect on mortality. It is unknown whether there is heterogeneity of treatment effect for digitalis therapy according to predicted risk of heart failure hospitalization.Methods And ResultsWe conducted a post hoc analysis of the Digitalis Investigator Group (DIG) studies, randomized controlled trials of digoxin vs placebo in participants with heart failure and left ventricular ejection fraction ≤45% (main DIG study, n = 6800) or >45% (ancillary DIG study, n = 988). Using a previously derived multistate model to risk-stratify DIG study participants, we determined the differential treatment effect on hospitalization and mortality outcomes. There was a 13% absolute reduction in the risk of any heart failure hospitalizations (39% vs 52%; odds ratio 0.58; 95% confidence interval 0.47-0.71) in the digoxin vs placebo arms in the highest-risk quartile, compared with a 3% absolute risk reduction for any heart failure hospitalization (17% vs 20%; odds ratio 0.84; 95% confidence interval, 0.66-1.08) in the lowest-risk quartile. There were 12 fewer total all-cause hospitalizations per 100 person-years in the highest-risk quartile compared with an increase of 8 hospitalizations per 100 person-years in the lowest-risk quartile. There was neutral effect of digoxin on mortality in all risk quartiles and no interaction between baseline risk and the effect of digoxin on mortality (P = .94).ConclusionsParticipants in the DIG study at higher risk of hospitalization as identified by a multistate model were considerably more likely to benefit from digoxin therapy to reduce heart failure hospitalization.Copyright © 2018 Elsevier Inc. All rights reserved.

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