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Effects of digoxin at low serum concentrations on mortality and hospitalization in heart failure: a
Ali Ahmed1, Bertram Pitt, Shahbudin H Rahimtoola
1University of Alabama at Birmingham, 1530 3rd Ave South, CH-19, Ste-219 and VA Medical Center, Birmingham, AL 35294-2041, USA. aahmed@uab.edu
Insights
Low-dose digoxin significantly reduces mortality and hospitalizations in heart failure (HF) patients. This study confirms digoxin
Area of Science:
- Cardiology
- Pharmacology
- Clinical Research
Background:
- Heart failure (HF) management often involves digoxin.
- Low serum digoxin concentrations (SDC) are associated with reduced mortality and hospitalizations in HF.
- Previous studies lacked propensity-matched analysis for cause-specific outcomes.
Purpose of the Study:
- To evaluate the effect of digoxin at low SDC on cause-specific outcomes in HF patients using a propensity-matched cohort.
- To analyze mortality and hospitalization rates in relation to digoxin treatment.
Main Methods:
- Analysis of 4843 ambulatory chronic HF patients from the Digitalis Investigation Group trial.
- Propensity score matching was used to compare 982 patients with low SDC digoxin to 982 placebo patients.
- Matched Cox regression analyses determined the impact of low SDC digoxin on various outcomes.
Main Results:
- Low SDC digoxin significantly reduced all-cause mortality (HR 0.81, P=0.028) and cardiovascular hospitalizations (HR 0.82, P=0.010).
- Specific reductions were observed for HF mortality (HR 0.65, P=0.015) and HF hospitalizations (HR 0.63, P<0.0001).
- Low-dose digoxin (≤0.125 mg/day) was the strongest predictor of achieving low SDC.
Conclusions:
- Digoxin, when administered at low SDC, offers significant benefits in reducing mortality and hospitalizations for ambulatory chronic HF patients.
- The findings support the continued use of digoxin at carefully monitored low concentrations in HF management.
- Low-dose digoxin is a key factor in achieving therapeutic low SDC levels.
Background:
In heart failure (HF), digoxin at low serum digoxin concentrations (SDC) reduces all-cause mortality and HF hospitalizations. However, the effects of digoxin on other cause-specific outcomes have not been studied in a propensity-matched cohort.
Methods:
The Digitalis Investigation Group trial, conducted during 1991-1993, enrolled 7788 ambulatory chronic HF patients. This analysis focuses on 4843 patients: 982 receiving digoxin with low (0.5-0.9 ng/ml) SDC at one month, and 3861 receiving placebo and alive at one month. Propensity scores for low SDC, calculated using a non-parsimonious multivariable logistic regression model, were used to match 982 low-SDC patients with 982 placebo patients. Matched Cox regression analyses were used to determine the effect of digoxin at low SDC on outcomes.
Results:
All-cause mortality occurred in 315 placebo (rate, 1071/10,000 person-years) and 288 low-SDC digoxin (rate, 871/10,000 person-years) patients, respectively, during 2940 and 3305 years of follow up (hazard ratio {HR}, 0.81, 95% confidence interval {CI}, 0.68-0.98; p=0.028). Cardiovascular hospitalizations occurred in 493 placebo (2359/10,000 person-year) and 471 low-SDC digoxin (1963/10,000 person-year) patients, respectively during 2090 and 2399 years of follow up (HR, 0.82, 95% CI, 0.70-0.95; P=0.010). Low-SDC digoxin to placebo HR (95%CI) for HF mortality and HF hospitalizations were respectively, 0.65 (0.45-0.92; P=0.015) and 0.63 (0.52-0.77; P<0.0001). Low-dose digoxin (< or = 0.125 mg/day) was the strongest independent predictor of low SDC (adjusted odd ratio, 2.07, 95% CI 1.54-2.80).
Conclusions:
Digoxin at low SDC significantly reduced mortality and hospitalizations in ambulatory chronic systolic and diastolic HF patients.
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