Digoxin and reduction in mortality and hospitalization in geriatric heart failure: importance of low doses and low serum concentrations

Abstract

Background: Digoxin reduces hospitalizations due to heart failure (HF) and may also reduce mortality at low serum digoxin concentrations (SDC). Most HF patients are > or = 65 years, yet the effects of digoxin on outcomes in these patients have not been well studied.

Methods: Of the 7788 ambulatory chronic HF patients in normal sinus rhythm in the Digitalis Investigation Group trial (1991-1995), 5548 (2890 were > or = 65 years) were alive at 1 month and were either receiving placebo or had data on SDC. Of these patients, 982 had low (0.5-0.9 ng/mL) and 705 had high (> or = 1 ng/mL) SDC.

Results: Among patients > or = 65 years, compared with 38% placebo patients, 34% low SDC patients died during 39 months of median follow-up (adjusted hazard ratio [AHR] = 0.81; 95% confidence interval [CI] = 0.68-0.96; p =.017). All-cause hospitalizations occurred in 70% of placebo and 68% of low-SDC patients (AHR = 0.86; 95% CI = 0.76-0.98; p =.019). Reduction in hospitalizations for HF occurred in both low and high SDC groups. High SDC was not independently associated with all-cause hospitalization or all-cause mortality. Age, impaired renal function, and pulmonary congestion reduced the odds of low SDC. Low-dose digoxin (< or = 0.125 mg/d) was the strongest independent predictor of low SDC (adjusted odd ratio = 2.37; 95% CI = 1.65-3.39); p <.0001).

Conclusions: Digoxin at low SDC was associated with a reduction in mortality and hospitalization in chronic geriatric HF, and low-dose digoxin was the strongest predictor of low SDC.

Figure 1

Kaplan Meier plots for all-cause mortality in heart failure patients (a) < 65 years and (b) ≥ 65 years

Figure 2

Kaplan Meier plots for hospitalization due to worsening heart failure in patients (a) <65 years and (b) ≥ 65 years

Figure 3

Independent predictors of low (0.5 – 0.9 ng/ml) serum digoxin concentrations among patients < 65 years (left panel: n=806; median age, 58 years) and ≥ 65 years (right panel: n=881; median age, 72 years) [Chronic kidney disease=estimated glomerular filtration rate <60 ml/m/1.73 square meters; OR=odds ratio, CI=confidence interval