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Digoxin Benefit Varies by Risk of Heart Failure Hospitalization: Applying the Tufts MC HF Risk Model.
Pubmed ID: 29284111
Pubmed Central ID: PMC7643562
Journal: The American journal of medicine
Publication Date: June 1, 2018
MeSH Terms: Humans, Male, Female, Aged, Risk Factors, Middle Aged, Heart Failure, Hospitalization, Treatment Outcome, Cardiotonic Agents, Digoxin
Grants: U01 NS086294, 1IP2PI000722-01
Authors: Kent DM, Konstam MA, Upshaw JN, van Klaveren D
Cite As: Upshaw JN, van Klaveren D, Konstam MA, Kent DM. Digoxin Benefit Varies by Risk of Heart Failure Hospitalization: Applying the Tufts MC HF Risk Model. Am J Med 2018 Jun;131(6):676-683.e2. Epub 2017 Dec 25.
Studies:
- Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes (AIM-HIGH)
- Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D)
- Coronary Artery Surgery Study (CASS)
- Digitalis Investigation Group (DIG)
- Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION)
- Post Coronary Artery Bypass Graft Study (CABG)
- Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)
- Systolic Blood Pressure Intervention Trial (SPRINT)
- Systolic Blood Pressure Intervention Trial Primary Outcome Paper (SPRINT-POP) Data
- Thrombolysis in Myocardial Ischemia Trial III (TIMI III)
- Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT)
Abstract
BACKGROUND: Digoxin 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 RESULTS: We 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). CONCLUSIONS: Participants 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.