Digoxin and reduction in mortality and hospitalization in heart failure: a comprehensive post hoc analysis of the DIG trial

Ahmed, Ali; Rich, Michael W.; Love, Thomas E.; Lloyd‐Jones, Donald M.; Aban, Inmaculada; Colucci, Wilson S.; Adams, Kirkwood F.; Gheorghiade, Mihai

doi:10.1093/eurheartj/ehi687

Cited by 333 publications

(211 citation statements)

References 42 publications

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“…As frequent hospitalisations are among the hallmarks of ACHF, digoxin is indicated in most patients with ACHF. Further analyses have indicated different effects of digoxin on mortality, with a reduction versus placebo at low serum digoxin levels, and no effect at higher plasma levels [55]. However, since renal impairment is frequent in ACHF, daily dosage should be adapted accordingly.…”

Section: Digoxinmentioning

confidence: 99%

Advanced chronic heart failure: A position statement from the Study Group on Advanced Heart Failure of the Heart Failure Association of the European Society of Cardiology

Metra

Ponikowski²,

Dickstein

et al. 2007

European J of Heart Fail

346

240

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Therapy has improved the survival of heart failure (HF) patients. However, many patients progress to advanced chronic HF (ACHF). We propose a practical clinical definition and describe the characteristics of this condition.Patients that are generally recognised as ACHF often exhibit the following characteristics: 1) severe symptoms (NYHA class III to IV); 2) episodes with clinical signs of fluid retention and/or peripheral hypoperfusion; 3) objective evidence of severe cardiac dysfunction, shown by at least one of the following: left ventricular ejection fraction b 30%, pseudonormal or restrictive mitral inflow pattern at Dopplerechocardiography; high left and/or right ventricular filling pressures; elevated B-type natriuretic peptides; 4) severe impairment of functional capacity demonstrated by either inability to exercise, a 6-minute walk test distance b 300 m or a peak oxygen uptake b 12-14 ml/kg/min; 5) history of N1 HF hospitalisation in the past 6 months; 6) presence of all the previous features despite optimal therapy. This definition identifies a group of patients with compromised quality of life, poor prognosis, and a high risk of clinical events. These patients deserve effective therapeutic options and should be potential targets for future clinical research initiatives.

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Section: Digoxinmentioning

confidence: 99%

Advanced chronic heart failure: A position statement from the Study Group on Advanced Heart Failure of the Heart Failure Association of the European Society of Cardiology

Metra

Ponikowski²,

Dickstein

et al. 2007

European J of Heart Fail

346

240

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“…Serum digoxin concentration (SDC) is an important predictor of therapeutic and adverse effects of digoxin, and was measured in a random subset of DIG participants. [5][6][7]9 Of the 1666 patients continued on digoxin, 457 had low (0.5-0.9 ng/ml) and 340 had high (≥1.0 ng/ml) SDC after 1 month of therapy, and of the 1699 patients in the placebo group, whose digoxin was discontinued, 1674 were alive at 1 month. Two patients randomized to placebo were censored during the first month after randomization and none had any hospitalizations during that period.…”

Section: Methodsmentioning

confidence: 99%

Effects of Discontinuation of Digoxin Versus Continuation at Low Serum Digoxin Concentrations in Chronic Heart Failure

Ahmed¹,

Gambassi²,

Weaver³

et al. 2007

The American Journal of Cardiology

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Discontinuation of digoxin is associated with worsening heart failure (HF) symptoms. However, the long-term effects of discontinuation of chronic digoxin therapy on mortality and morbidity in HF have not been well studied. Of the 7788 Digoxin Investigation Group trial participants, 3365 were receiving digoxin before randomization. During the trial, digoxin was continued in 1666 patients and discontinued in 1699 patients. Using multivariable Cox regression analyses, we at first determined the effect of discontinuation of digoxin on mortality and hospitalization during 39.7 months of median follow up. Of the 1666 patients continued on digoxin, 457 had low (0.5-0.9 ng/ml) and 340 had high (≥1.0 ng/ml) serum digoxin concentrations (SDC) after 1 month of therapy and of the 1699 patients whose digoxin was discontinued, 1674 were alive at 1 month. We examined the effects of continuation of digoxin at low or high SDC. Compared with continuation of chronic digoxin therapy, discontinuation of digoxin was associated with significant increase in all-cause hospitalization (adjusted hazard ratio {AHR}=1.18; 95% confidence interval {CI}=1.09-1.28; P<0.0001) and HF hospitalization (AHR=1.35; 95% CI=1.20-1.51; P<0.0001), but had no effect on all cause mortality (AHR=1.06; 95% CI=0.95-1.19; P=0.272). Continuation of digoxin at low SDC, on the other hand, was associated with reduction in all-cause mortality (AHR=0.75; 95% CI=0.63-0.90; P=0.002), allcause hospitalization (AHR=0.80; 95% CI=0.71-0.91; P=0.001) and HF hospitalization (AHR=0.60; 95% CI=0.50-0.73; P<0.0001). In conclusion, continuation of chronic digoxin therapy at low SDC was associated with reduction in mortality and hospitalization in ambulatory chronic HF patients receiving background therapy with ACE inhibitors and diuretics. KeywordsHeart failure; digoxin; discontinuation; mortality; hospitalization The American College of Cardiology / American Heart Association (ACC/AHA) guideline for chronic heart failure (HF) recommends continuation of long-term digoxin therapy in HF patients who are already receiving this drug. 1 Discontinuation of digoxin is associated with worsening heart failure (HF) symptoms. 2-4 However, little is known about the long-term effect of discontinuation of chronic digoxin therapy on mortality and morbidity in patients with ambulatory chronic heart failure (HF). Even less is known about the effect of continuation of long-term digoxin therapy at low serum digoxin concentration (SDC). In the Digitalis Investigation Group (DIG) trial, 3365 (43%) of the 7788 patients were receiving digoxin at the time of enrollment. 5 These patients were randomized to discontinue (placebo arm) or continue (digoxin arm) their chronic digoxin therapy. Data on SDC were collected in a random subset of DIG participants and post hoc analysis using SDC data suggest that the effect of digoxin on outcomes in HF may be dependent on SDC. 6,7 These provide a unique opportunity to rapidly and efficiently determine the long-term effect of discontinuation of digoxin as we...

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“…However, Rathore et al 7 have shown that all-cause mortality is higher in patients with serum digoxin concentration > 1.2ng/ ml in comparison to patients with serum digoxin concentrations ≤ 1.2ng/ml. More recently, studies have suggested that survival may be improved in patients in whom digoxin serum concentrations are lower (0.5 to 1.0ng/ml) than those previously recommended (0.8 to 2.0ng/ml) [8][9][10] .…”

Section: Palavrasmentioning

confidence: 97%

“…Digoxin was administered as previously described, in the morning, by oral route, according to age (0.125mg/day per patients aged > 65 years, and 0.25mg/day per patient aged < 65 years) 8 .…”

Section: Patientsmentioning

confidence: 99%

Digoxin serum levels in patients with Chagas' cardiomyopathy and heart failure

Ferrari

Bestetti

Cardinalli-Neto

et al. 2010

Rev. Soc. Bras. Med. Trop.

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Introduction: The purpose of this study was to determine digoxin serum concentrations in patients with Chagas' cardiomyopathy with chronic heart failure, because little is known concerning this laboratory test in patients with this condition. Methods: This study focuses on 29 (29%) out of 101 patients with chronic heart failure secondary to Chagas' cardiomyopathy receiving digoxin therapy. Digoxin was measured by the immune-enzymatic method. Results: New York Heart Association Functional Class III/IV was noted in 13 (45%) patients. The mean potassium serum level was 4.3± 0.5mEq/L, mean creatinine serum levels 1.4± 0.3dg/100ml, and left ventricular ejection fraction 34.7± 13.8%. The median digoxin serum level was 1.27 (0.55; 1.79)ng/ml. Sixteen (55%) patients had digoxin serum levels higher than 1.0ng/ml. Abnormal digoxin serum levels were verified in 13 (45%) patients. Digoxin serum levels correlated moderately with creatinine serum levels (r = 0.39; p≤ 0.03) and negatively with sodium serum levels (r= -0.38; p= 0.03). Conclusions: Digoxin serum concentration should be measured in patients with Chagas' cardiomyopathy with chronic heart failure receiving digoxin therapy due to the potential for digoxin toxicity.

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Digoxin and reduction in mortality and hospitalization in heart failure: a comprehensive post hoc analysis of the DIG trial

Abstract: Digoxin at SDC 0.5-0.9 ng/mL reduces mortality and hospitalizations in all HF patients, including those with preserved systolic function. At higher SDC, digoxin reduces HF hospitalization but has no effect on mortality or all-cause hospitalizations.

Cited by 333 publications

References 42 publications

Advanced chronic heart failure: A position statement from the Study Group on Advanced Heart Failure of the Heart Failure Association of the European Society of Cardiology

Advanced chronic heart failure: A position statement from the Study Group on Advanced Heart Failure of the Heart Failure Association of the European Society of Cardiology

Effects of Discontinuation of Digoxin Versus Continuation at Low Serum Digoxin Concentrations in Chronic Heart Failure

Digoxin serum levels in patients with Chagas' cardiomyopathy and heart failure

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