Digoxin for heart failure, obsolete or still useful?

    Authors

    Keywords

    digoxin, heart failure, ejection fraction, hospitalization

    DOI

    https://doi.org/10.15836/ccar2018.364

    Full Text

    Digoxin is a positive inotropic agent, the only one suitable for chronic oral administration in patients with systolic heart failure (HFrEF < 45-50%) with or without atrial fibrillation. Significant neurohumoral properties are also significant by suppressing the excessive activity of the sympathetic and renin-aldosterone system. Numerous studies confirm that it gives exceptional hemodynamic effects by increasing the left ventricular ejection fraction (LVEF), the cardiac index by reducing pulmonary capillary pressure. It slows down the heart function and neutralizes blood pressure. Therefore, unlike beta-blockers and ACEs/ARBs, it can safely be used in patients with lower blood pressure values. Digoxin is also associated with the improvement of the renal function, estimated by 20% increase in glomerular filtration. Therefore, unlike the renin-angiotensin-aldosterone system inhibitor, it can be used in patients with limiting renal function without the risk of further renal impairment. Digoxin has been the first choice drug for many years until the 1997 DIG trial proved that the drug does not reduce mortality in patients in III/IV stage according to NYHA with the values of LVEF ≤40% or those in the II stage according to the NYHA classification with LVEF≤ 30% regardless of the presence of atrial fibrillation, although it contributes to the reduction of the symptoms and frequency of inpatient treatment. ( 1 ) DIG study may not be criticized for not using beta-blockers and aldosterone antagonists in the heart failure therapy at that time and relatively high digoxin doses were prescribed, which are not common today. Only in the last decade, the use of digoxin in the treatment of HFrEF has decreased by two-thirds. According to the US GWTH-HF register of 250,000 patients with HFrEF, the frequency of use of digoxin recommended at the time of release was reduced from 33.1% in 2005 to 10.7% patients in 2014. ( 2 , 3 ) Current European (IIb recommendation level) and US guidelines (IIa recommendation level) recommend digoxin in patients with HFrEF who have permanent symptoms despite optimal therapy in order to reduce the incidence of hospitalization. When using digoxin, small doses equivalent to serum concentrations <0.9 ng/ml are recommended. In studies with stable HFrEF, the discontinuation of the digoxin therapy was followed by worsening of symptoms, where the physical stress tolerance was reduced and LVEF fall was recorded. In extremely severe cases of HFrEF, the introduction of digoxin managed to remove the mechanical circulatory support and intravenous inotropic drugs. For the last twenty years, the heart failure treatment has changed considerably. Owing to modern therapy including the mechanical support and the heart transplantation, the industry shows no interest in digoxin and is very likely that some other DIG volume clinical trial will be sponsored. We should also emphasize the fact that digoxin is a very cheap drug. A clinician faces the dilemma of whether he should rely on the data quality resulting from clinical trials conducted more than two decades ago and before modern heart failure therapy was available or on the evidence from mostly observational studies. Digoxin is probably still justified in patients with severely advanced systolic dysfunction who are unable to tolerate high doses of drugs due to limit values ​​of blood pressure, renal function. The drug should also be used to reduce recurrent hospitalization, and the today’s patient with systolic heart failure is on the average 10 years older than the one in the DIG trial and a daily dose of 0.10 may be adequate for a larger number of patients.

    Cardiologia Croatica
    Back to search

    Digoxin for heart failure, obsolete or still useful?

    Extended Abstract
    Issue11-12
    Published
    Pages364-365
    PDF via DOIhttps://doi.org/10.15836/ccar2018.364
    digoxin
    heart failure
    ejection fraction
    hospitalization

    Authors

    Vjeran Nikolić Heitzler*ORCIDZagreb, Croatia

    Full Text

    Digoxin is a positive inotropic agent, the only one suitable for chronic oral administration in patients with systolic heart failure (HFrEF < 45-50%) with or without atrial fibrillation. Significant neurohumoral properties are also significant by suppressing the excessive activity of the sympathetic and renin-aldosterone system. Numerous studies confirm that it gives exceptional hemodynamic effects by increasing the left ventricular ejection fraction (LVEF), the cardiac index by reducing pulmonary capillary pressure. It slows down the heart function and neutralizes blood pressure. Therefore, unlike beta-blockers and ACEs/ARBs, it can safely be used in patients with lower blood pressure values. Digoxin is also associated with the improvement of the renal function, estimated by 20% increase in glomerular filtration. Therefore, unlike the renin-angiotensin-aldosterone system inhibitor, it can be used in patients with limiting renal function without the risk of further renal impairment. Digoxin has been the first choice drug for many years until the 1997 DIG trial proved that the drug does not reduce mortality in patients in III/IV stage according to NYHA with the values of LVEF ≤40% or those in the II stage according to the NYHA classification with LVEF≤ 30% regardless of the presence of atrial fibrillation, although it contributes to the reduction of the symptoms and frequency of inpatient treatment. ( 1 ) DIG study may not be criticized for not using beta-blockers and aldosterone antagonists in the heart failure therapy at that time and relatively high digoxin doses were prescribed, which are not common today. Only in the last decade, the use of digoxin in the treatment of HFrEF has decreased by two-thirds. According to the US GWTH-HF register of 250,000 patients with HFrEF, the frequency of use of digoxin recommended at the time of release was reduced from 33.1% in 2005 to 10.7% patients in 2014. ( 2 , 3 ) Current European (IIb recommendation level) and US guidelines (IIa recommendation level) recommend digoxin in patients with HFrEF who have permanent symptoms despite optimal therapy in order to reduce the incidence of hospitalization. When using digoxin, small doses equivalent to serum concentrations <0.9 ng/ml are recommended. In studies with stable HFrEF, the discontinuation of the digoxin therapy was followed by worsening of symptoms, where the physical stress tolerance was reduced and LVEF fall was recorded. In extremely severe cases of HFrEF, the introduction of digoxin managed to remove the mechanical circulatory support and intravenous inotropic drugs. For the last twenty years, the heart failure treatment has changed considerably. Owing to modern therapy including the mechanical support and the heart transplantation, the industry shows no interest in digoxin and is very likely that some other DIG volume clinical trial will be sponsored. We should also emphasize the fact that digoxin is a very cheap drug. A clinician faces the dilemma of whether he should rely on the data quality resulting from clinical trials conducted more than two decades ago and before modern heart failure therapy was available or on the evidence from mostly observational studies. Digoxin is probably still justified in patients with severely advanced systolic dysfunction who are unable to tolerate high doses of drugs due to limit values ​​of blood pressure, renal function. The drug should also be used to reduce recurrent hospitalization, and the today’s patient with systolic heart failure is on the average 10 years older than the one in the DIG trial and a daily dose of 0.10 may be adequate for a larger number of patients.