digoxin and Heart-Failure--Systolic

Digoxin remains one of the oldest therapies for heart failure; however, its safety and efficacy have been controversial since its initial use. Questions that remain include the clinical efficacy of digoxin when added to contemporary medical therapy, when and if it should be added, and how to minimize adverse effects. In this review, we will summarize recent data on the use of digoxin in systolic heart failure and address some of the controversies regarding the role of digoxin in the modern era of heart failure treatment.

Topics: Cardiotonic Agents; Digoxin; Heart Failure, Systolic; Humans; Treatment Outcome

The use of digoxin in the therapy of systolic heart failure and certain supraventricular tachycardias is controversial. This review of the art and science of digoxin presents information needed by physicians considering digoxin therapy for these common cardiovascular disorders.

Topics: Aged; Cardiotonic Agents; Digoxin; Heart Failure, Systolic; Humans; Tachycardia, Supraventricular

Digoxin improves exercise tolerance and reduces hospitalizations in patients with systolic heart failure, but its use has declined progressively for the past two decades. The Digitalis Investigation Group trial showed that digoxin reduced hospitalizations but had a neutral effect on total mortality. There was evidence that mortality caused by worsening heart failure was less, but there was also a signal suggesting an increase in other cardiac (presumed arrhythmic) death. Use of digoxin has declined substantially and recent guideline recommendations have significantly de-emphasized the importance of this drug in the management of heart failure. Two developments suggest that re-evaluation of the contemporary role of digoxin in the management of heart failure with reduced ejection fraction is warranted. First, heart failure remains progressive, characterized by chronic debility, exercise intolerance, and frequent and costly hospitalizations, despite evidence-based drug and device therapies that prolong survival. Health economics have made reducing hospitalizations in patients with heart failure a major priority. Second, a strong association has emerged between serum concentration and the safety and efficacy of digoxin, which indicates a change in our approach to dosing this agent is needed. Experimental and clinical results suggest that optimizing therapeutic benefit and avoiding harm means dosing to achieve low serum digoxin concentrations (0.5-0.9 ng/mL). Digoxin is an inexpensive agent and the totality of evidence indicates that it reduces hospitalizations and improves symptoms safely when dosed to achieve low serum concentrations. These findings suggest digoxin should have a more prominent therapeutic role in patients with heart failure and reduced ejection fraction.

Topics: Cardiotonic Agents; Cause of Death; Chronic Disease; Digoxin; Disease Management; Dose-Response Relationship, Drug; Drug Monitoring; Exercise Tolerance; Heart Failure, Systolic; Hospitalization; Humans; Mortality; Outcome Assessment, Health Care; Practice Guidelines as Topic; Stroke Volume

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Cardiovascular Agents; Chronic Disease; Digoxin; Drug Combinations; Heart Failure; Heart Failure, Systolic; Humans; Hydralazine; Isosorbide Dinitrate; Ivabradine; Mineralocorticoid Receptor Antagonists

To review relevant literature supporting the use of β-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), diuretics, digoxin, aldosterone antagonists, and vasodilators in the management of heart failure in an elderly patient population aged ≥65 years.. PubMed, EMBASE, and MEDLINE searches (January 1960-April 2010) were utilized to identify primary literature using the key terms heart failure, treatment, and elderly. Additionally, reference citations from publications identified were utilized, as well as the American College of Cardiology/American Heart Association (ACC/AHA) Guidelines for the Diagnosis and Management of Chronic Heart Failure in the Adult.. Primary and tertiary literature, including subgroup analyses, published in English and relating to the use of pharmacotherapy in the treatment of systolic heart failure in the elderly was reviewed.. The aging of the US population is creating a higher prevalence of systolic heart failure in the elderly. Most clinical trials have established the mortality and morbidity benefit of pharmacotherapy in heart failure in nonelderly patients; however, the current ACC/AHA guidelines do not clearly delineate this benefit in persons ≥65 years of age.. Clinical trial data, based on limited numbers of individuals aged ≥65 years, suggest that use of β-blockers, ACE inhibitors, ARBs, aldosterone antagonists, and vasodilators (hydralazine/nitrates) have similar mortality benefit to that observed in younger patients. As supported in the ACC/AHA guidelines, these agents should be prescribed with clinical judgment to all elderly patients, with close monitoring for adverse events. Future clinical trials with greater inclusion of patients ≥65 years will help to elucidate the magnitude of benefits of optimal pharmacotherapy on mortality and morbidity rates in this population.

Topics: Adrenergic beta-Antagonists; Age Factors; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Cardiovascular Agents; Digoxin; Diuretics; Evidence-Based Medicine; Heart Failure, Systolic; Humans; Mineralocorticoid Receptor Antagonists; Vasodilator Agents

Although women account for a significant proportion of the growing heart failure epidemic, they have been poorly represented in clinical trials. As emerging epidemiologic data reveal a growing prevalence and burden of disease among women, it is increasingly important that treating physicians and researchers recognize sex-based differences. Despite the overall incidence of heart failure being lower in women compared with men, the magnitude of improvement in survival over the last several decades has been less apparent in women. Women with heart failure are more likely to be older, have preserved systolic function and nonischemic cardiomyopathy. While clinical trials have demonstrated improved outcomes among heart failure patients, they have predominantly included men, yielding results that are sometimes inadequately powered to detect a benefit for women. Without adequate representation of women in clinical trials, one cannot assume that the same level of therapeutic evidence also applies to women. Nonetheless, it appears that beta-blockers and angiotensin-converting enzyme inhibitors provide the same survival benefits in women with systolic dysfunction as in men. In addition, some studies suggest that angiotensin-receptor blockers may lead to a better survival in women when compared with angiotensin-converting enzyme inhibitors. Focused research is needed to understand and guide the management of women with heart failure.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Comorbidity; Digoxin; Female; Heart Failure, Diastolic; Heart Failure, Systolic; Hormone Replacement Therapy; Humans; Male; Risk Factors; Sex Factors; United States

Heart failure is a leading cause of hospital admission and readmission in older adults. The new United States healthcare reform law has created provisions for financial penalties for hospitals with higher than expected 30-day all-cause readmission rates for hospitalized Medicare beneficiaries aged ≥65 years with heart failure. We examined the effect of digoxin on 30-day all-cause hospital admission in older patients with heart failure and reduced ejection fraction.. In the main Digitalis Investigation Group trial, 6800 ambulatory patients with chronic heart failure (ejection fraction ≤45%) were randomly assigned to digoxin or placebo. Of these, 3405 were aged ≥65 years (mean age, 72 years; 25% were women; 11% were nonwhite). The main outcome in the current analysis was 30-day all-cause hospital admission.. In the first 30 days after randomization, all-cause hospitalization occurred in 5.4% (92/1693) and 8.1% (139/1712) of patients in the digoxin and placebo groups, respectively, (hazard ratio {HR} when digoxin was compared with placebo, 0.66; 95% confidence interval {CI}, 0.51-0.86; P=.002). Digoxin also reduced both 30-day cardiovascular (3.5% vs 6.5%; HR, 0.53; 95% CI, 0.38-0.72; P<.001) and heart failure (1.7 vs 4.2%; HR, 0.40; 95% CI, 0.26-0.62; P<.001) hospitalizations, with similar trends for 30-day all-cause mortality (0.7% vs 1.3%; HR, 0.55; 95% CI, 0.27-1.11; P=.096). Younger patients were at lower risk of events but obtained similar benefits from digoxin.. Digoxin reduces 30-day all-cause hospital admission in ambulatory older patients with chronic systolic heart failure. Future studies need to examine its effect on 30-day all-cause hospital readmission in hospitalized patients with acute heart failure.

Topics: Aged; Cardiotonic Agents; Digoxin; Female; Heart Failure, Systolic; Hospitalization; Humans; Male; Patient Protection and Affordable Care Act; Treatment Outcome; United States

In the setting of low-flow/low-gradient aortic stenosis (LF/LGAS), outcomes of pseudo-severe aortic stenosis (AS) remain poorly described. This study was aimed to assess the outcome of patients with pseudo-severe AS under conservative treatment.. Among 305 patients from the European Registry of LF/LGAS, the outcomes of the 107 patients followed under conservative treatment were analysed. Based on the results of dobutamine echocardiography, patients were divided into group IA [left ventricular (LV) contractile reserve present with true-severe AS, n = 43], group IB [pseudo-severe AS (n = 29) defined as LV contractile reserve with a final aortic valve area ≥1.2 cm(2) and a mean transaortic pressure gradient <40 mmHg at peak dobutamine infusion], or group II (exhausted LV contractile reserve, n = 35). The rate of death within 5 years was significantly lower in the group IB (43 ± 11%, n = 10), when compared with the group IA (91 ± 6%, n = 33; P = 0.001) and the group II (100%, n = 23; P < 0.001). The Cox proportional hazard model analysis demonstrated that the hazard ratio for death in the group IB remained significantly lower than in the other groups, even after adjustment for currently established risk factors. Furthermore, the 5-year survival of pseudo-severe AS patients was comparable with that of propensity-matched patients with systolic heart failure and no evidence of valve disease.. In patients with pseudo-severe AS, the 5-year survival under conservative treatment is better than in true-severe AS and comparable with that of propensity-matched patients with LV systolic dysfunction and no evidence of valve disease. Further studies are needed to define optimal therapeutic management in these patients.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Aortic Valve Stenosis; Digoxin; Echocardiography, Stress; Female; Heart Failure, Systolic; Humans; Kaplan-Meier Estimate; Male; Prospective Studies; Treatment Outcome

Heart failure (HF) treatment guided by amino-terminal pro-B type natriuretic peptide (NT-proBNP) may reduce cardiovascular event rates compared to standard-of-care (SOC) management. Comprehensive understanding regarding effect of NT-proBNP guided care on patient-reported quality of life (QOL) remains unknown.. One hundred fifty-one subjects with HF due to left ventricular systolic dysfunction were randomized to either SOC HF management or care with a goal to reduce NT-proBNP values ≤1000 pg/mL. Effects of HF on QOL were assessed using the Minnesota Living with HF Questionnaire (MLHFQ) quarterly, with change (Δ) in score assessed across study procedures and as a function of outcome.. Overall, baseline MLHFQ score was 30. Across study visits, QOL improved in both arms, but was more improved and sustained in the NT-proBNP arm (repeated measures P = .01); NT-proBNP patients showing greater reduction in MLHFQ score (-10.0 vs -5.0; P = .05), particularly in the physical scale of the questionnaire. Baseline MLHFQ scores did not correlate with NT-proBNP; in contrast, ∆MLHFQ scores modestly correlated with ∆NT-proBNP values (ρ = .234; P = .006) as did relative ∆ in MLHFQ score and NT-proBNP (ρ = .253; P = .003). Considered in tertiles, less improvement in MLHFQ scores was associated with a higher rate of HF hospitalization, worsening HF, and cardiovascular death (P = .001).. We describe novel associations between NT-proBNP concentrations and QOL scores among patients treated with biomarker guided care. Compared to SOC HF management, NT-proBNP guided care was associated with greater and more sustained improvement in QOL (Clinical Trial Registration: www.clinicaltrials.govNCT00351390).

Topics: Adrenergic beta-Antagonists; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Cardiovascular Agents; Chronic Disease; Digoxin; Diuretics; Female; Follow-Up Studies; Health Status; Heart Failure, Systolic; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Peptide Fragments; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

Prior Studies showed mixed results in association of digoxin use with all-cause mortality (ACM). The aim of this analysis is to identify the impact of digoxin use on ACM in a contemporary heart failure (HF) cohort treated with guideline based therapy.. We included 2298 consecutive patients seen in an HF clinic between 2000 and 2015. Patients were considered to be a digoxin user if he/she received digoxin at any point during the enrollment period in the HF clinic. Patients were matched based on digoxin utility using propensity matching in 2-3:1 fashion. The primary outcome was ACM.. Of 2298 patients, 325 digoxin users were matched with 750 non-digoxin users. The Matched cohort did not have differences among demographics and clinical variables except for worse HF symptomatology and increased prevalence of atrial fibrillation. Overall, the prevalence of the use of guideline suggested therapies was 96%. After a median follow-up duration of 4years (IQR 2-6years), digoxin use was associated with increased ACM (21.8% versus 12.9%, unadjusted HR=1.81; 95% CI=1.33 to 2.45; p=0.001). This association remained significant after adjusting for the propensity score, atrial fibrillation, ejection fraction, and New York HF Class (HR=1.74; 95% CI=1.20 to 2.38; p<0.0001).. In this analysis of well-treated HF patients, digoxin was associated with increased ACM. Further randomized controlled trials are needed to determine whether digoxin therapy should be used in well-treated HF patients. Until then, routine use of digoxin in clinical practice should be discouraged.

Topics: Adult; Aged; Cardiotonic Agents; Chronic Disease; Cohort Studies; Digoxin; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Propensity Score; Survival Rate; Treatment Outcome

Topics: Cardiotonic Agents; Digoxin; Female; Heart Failure, Systolic; Hospitalization; Humans; Male

Topics: Cardiotonic Agents; Digoxin; Female; Heart Failure, Systolic; Hospitalization; Humans; Male

Heart failure is the leading cause for hospital readmission, the reduction of which is a priority under the Affordable Care Act. Digoxin reduces 30-day all-cause hospital admission in chronic systolic heart failure. Whether digoxin is effective in reducing readmission after hospitalization for acute decompensation remains unknown.. Of the 5153 Medicare beneficiaries hospitalized for acute heart failure and not receiving digoxin, 1054 (20%) received new discharge prescriptions for digoxin. Propensity scores for digoxin use, estimated for each of the 5153 patients, were used to assemble a matched cohort of 1842 (921 pairs) patients (mean age, 76 years; 56% women; 25% African American) receiving and not receiving digoxin, who were balanced on 55 baseline characteristics.. Thirty-day all-cause readmission occurred in 17% and 22% of matched patients receiving and not receiving digoxin, respectively (hazard ratio [HR] for digoxin, 0.77; 95% confidence interval [CI], 0.63-0.95). This beneficial association was observed only in those with ejection fraction <45% (HR 0.63; 95% CI, 0.47-0.83), but not in those with ejection fraction ≥ 45% (HR 0.91; 95% CI, 0.60-1.37; P for interaction, .145), a difference that persisted throughout the first 12 months postdischarge (P for interaction, .019). HRs (95% CIs) for 12-month heart failure readmission and all-cause mortality were 0.72 (0.61-0.86) and 0.83 (0.70-0.98), respectively.. In Medicare beneficiaries with systolic heart failure, a discharge prescription of digoxin was associated with lower 30-day all-cause hospital readmission, which was maintained at 12 months, and was not at the expense of higher mortality. Future randomized controlled trials are needed to confirm these findings.

Topics: Aged; Aged, 80 and over; Cardiotonic Agents; Case-Control Studies; Chronic Disease; Digoxin; Drug Administration Schedule; Female; Heart Failure, Systolic; Humans; Male; Medicare; Patient Discharge; Patient Readmission; Treatment Outcome; United States

Topics: Cardiotonic Agents; Digoxin; Female; Heart Failure, Systolic; Hospitalization; Humans; Male

Topics: Cardiotonic Agents; Digoxin; Female; Heart Failure, Systolic; Hospitalization; Humans; Male

Topics: Cardiotonic Agents; Digoxin; Female; Heart Failure, Systolic; Humans; Male; Medicare; Patient Readmission

Topics: Cardiotonic Agents; Digoxin; Female; Heart Failure, Systolic; Humans; Male

Clinical guidelines recommend digoxin for patients with symptomatic systolic heart failure (HF) receiving optimal medical therapy, but this recommendation is based on limited, older trial data. We evaluated the effectiveness and safety of digoxin in a contemporary cohort of patients with incident systolic HF.. We identified adults with incident systolic HF between 2006 and 2008 within Kaiser Permanente Northern California who had no prior digoxin use. We used multivariable extended Cox regression to examine the association between new digoxin use and risks of death and HF hospitalization, controlling for medical history, laboratory results, medications, HF disease severity, and the propensity for digoxin use. We also conducted analyses stratified by sex and concurrent β-blocker use. Among 2891 newly diagnosed patients with systolic HF, 529 (18%) received digoxin. During a median 2.5 years of follow-up, incident digoxin use was associated with higher rates of death (14.2 versus 11.3 per 100 person-years) and HF hospitalization (28.2 versus 24.4 per 100 person-years). In multivariable analysis, incident digoxin use was associated with higher mortality (hazard ratio, 1.72; 95% confidence interval, 1.25-2.36) but no significant difference in the risk of HF hospitalization (hazard ratio, 1.05; 95% confidence interval, 0.82-1.34). Results were similar in analyses stratified by sex and β-blocker use.. Digoxin use in patients with incident systolic HF was independently associated with a higher risk of death but no difference in HF hospitalization.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; California; Cardiotonic Agents; Chi-Square Distribution; Digoxin; Disease Progression; Drug Therapy, Combination; Female; Guideline Adherence; Health Maintenance Organizations; Heart Failure, Systolic; Hospitalization; Humans; Incidence; Male; Middle Aged; Multivariate Analysis; Practice Guidelines as Topic; Proportional Hazards Models; Risk Factors; Sex Factors; Time Factors; Treatment Outcome

The Scottish Intercollegiate Guidelines Network (SIGN) guideline 95 on the management of chronic heart failure (CHF) was published in February 2007, superseding SIGN guideline 35 of February 1999. The guideline promotes evidence based management of CHE.. To describe an existing service model and to review our level of concordance with SIGN guidelines.. We describe a model of a CHF service based in a district general hospital (DGH) in Scotland. We conducted a retrospective review on consecutive new referrals between August and November 2002, and a prospective review of new attendances between September 2005 and January 2006.. In 2002 and 2005/6, 49 and 45 patients were reviewed respectively, with 26 and 28 patients showing left ventricular systolic dysfunction on echocardiography. Median ages of patients were 81 and 79 years respectively. Angiotensin Converting Enzyme Inhibitor (ACEI) or Angiotensin II Receptor Blocker (AIIRB) therapy was in use in 23 (88.5%) and 24 (85.7%) patients respectively. The use of beta-blockers, digoxin and spironolactone was shown to have improved between both reviews.. We have been able to demonstrate an improving level of concordance with SIGN guidelines in a district general hospital (DGH) heart failure service model run by care of the elderly physicians and supported by specialist nurses.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Disease Management; Diuretics; Heart Failure, Systolic; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Medical Audit; Outpatient Clinics, Hospital; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prospective Studies; Retrospective Studies; Scotland; Spironolactone

Previous trials have shown that digoxin was beneficial in patients with heart failure (HF). However, these studies were conducted before the incorporation of beta blockers as standard therapy for patients with HF. The purpose of this study was to determine the effect of digoxin in patients with HF on a contemporary regimen of renin-angiotensin inhibition and beta blockade. In 347 almost exclusively men, data pertaining to the index hospitalization and occurrence of all-cause mortality or readmission for HF were collected. Cox proportional hazard modeling was used. Patients on digoxin therapy had a lower left ventricular (LV) ejection fraction (EF), higher prevalence of previous hospitalizations for HF and atrial fibrillation, and lower prevalence of hypertension. After adjustment for age, LVEF, history of HF hospitalizations, New York Heart Association class, presence of chronic renal insufficiency, presence of atrial fibrillation, and prescriptions for beta blockers and angiotensin converting enzyme inhibitors or angiotensin receptor blockers, HF hospitalizations (hazard ratio 1.08, 95% confidence interval [CI] 0.77 to 1.50, p = 0.66), total mortality (hazard ratio 1.03, 95% CI 0.78 to 1.35, p = 0.85), or the combined end point of HF hospitalization and total mortality (hazard ratio 1.11, 95% CI 0.81 to 1.53, p = 0.52) were not different in patients using digoxin compared with those not using digoxin. Clinical outcomes were not different in subgroups of patients with EF < or =25%, New York Heart Association class III or IV, atrial fibrillation, heart rate < or =60 beats/min, or patients on beta-blocker therapy. In conclusion, digoxin use was not associated with a decrease in HF hospitalizations or overall mortality rates in a cohort of hospitalized patients with HF with LV systolic dysfunction on contemporary background HF treatment including angiotensin-converting enzyme inhibitors and beta blockers.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Female; Heart Failure, Systolic; Humans; Male; Treatment Outcome

We sought to identify predictors of all-cause mortality for Chagas' disease patients with chronic systolic heart failure because they are virtually lacking in the current era of heart failure therapy.. This study focus on 127 patients with the diagnosis of chronic systolic heart failure secondary to Chagas' cardiomyopathy. Mean follow up was 25+/-19 months. Sixty-three (50%) patients died during the study period. Cox regression analysis showed lack of B-blocking agent use (p=0.002, hazard ratio=0.30, 95% Confidence Interval 0.14 to 0.64), serum sodium levels (p=0.01, hazard ratio=0.93, 95% Confidence Interval 0.87 to 0.98), left ventricular ejection fraction (p=0.02, hazard ratio=0.96, 95% Confidence Interval 0.93 to 0.99), digoxin treatment (p=0.04, hazard ratio=8.47, 95% Confidence Interval 1.13 to 62.52) and New York Heart Association Class IV on admission (p=0.034, hazard ratio=1.92, 95% Confidence Interval 1.02 to 3.51) independent predictors of all-cause mortality.. Lack of B-blocking agent use, serum sodium levels, left ventricular ejection fraction, digoxin treatment and New York Heart Association Class IV are independent predictors of all-cause mortality for patients with chronic heart failure secondary to Chagas' cardiomyopathy in the current era of heart failure therapy.

Topics: Adrenergic beta-Antagonists; Aged; Cardiotonic Agents; Cause of Death; Chagas Cardiomyopathy; Chronic Disease; Digoxin; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Regression Analysis; Risk Factors; ROC Curve; Sodium; Stroke Volume; Survival Analysis