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JACC. Heart Failure Apr 2024Medical treatment for heart failure with preserved ejection (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF) has weaker evidence compared with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Medical treatment for heart failure with preserved ejection (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF) has weaker evidence compared with reduced ejection fraction, despite recent trials with an angiotensin receptor neprilysin inhibitor (ARNI) and sodium glucose co-transporter 2 inhibitors (SGLT2is).
OBJECTIVES
The authors aimed to estimate the aggregate therapeutic benefit of drugs for HFmrEF and HFpEF.
METHODS
The authors performed a systematic review of MEDLINE, CENTRAL, and Web of Science for randomized trials including patients with heart failure (HF) and left ventricular ejection fraction (LVEF) >40%, treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (analyzed together as renin-angiotensin system inhibitors [RASi]), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), digoxin, ARNI, and SGLT2i. An additive component network meta-analysis was performed. The primary outcome was a composite of cardiovascular (CV) death and first hospitalization for heart failure (HHF); secondary outcomes were CV death, total HHF, and all-cause mortality.
RESULTS
The authors identified 13 studies with a total of 29,875 patients and a mean LVEF of 56.3% ± 8.7%. ARNI, MRA, and SGLT2i separately, but not RASi, BB, or digoxin, reduced the primary composite outcome compared with placebo. The combination of ARNI, BB, MRA, and SGLT2i was the most effective (HR: 0.47 [95% CI: 0.31-0.70]); this was largely explained by the triple combination of ARNI, MRA, and SGLT2i (HR: 0.56 [95% CI 0.43-0.71]). Results were similar for CV death (HR: 0.63 [95% CI 0.43-0.91] for ARNI, MRA, and SGLT2i) or total HHF (HR: 0.49 [95% CI 0.33-0.71] for ARNI, MRA, and SGLT2i) alone. In a subgroup analysis, only SGLT2i had a consistent benefit among all LVEF subgroups, whereas the triple combination had the greatest benefit in HFmrEF, robust benefit in patients with LVEF 50% to 59%, and a statistically marginal benefit in patients with LVEF ≥60%.
CONCLUSIONS
In patients with HF and LVEF>40%, the quadruple combination of ARNI, BB, MRA, and SGLT2i provides the largest reduction in the risk of CV death and HHF; driven by the robust effect of the triple combination of ARNI, MRA, and SGLT2i. The benefit was more pronounced in HFmrEF patients.
Topics: Humans; Angiotensin Receptor Antagonists; Digoxin; Heart Failure; Network Meta-Analysis; Stroke Volume; Treatment Outcome; Ventricular Function, Left; Randomized Controlled Trials as Topic
PubMed: 37656079
DOI: 10.1016/j.jchf.2023.07.014 -
The Canadian Journal of Cardiology Nov 2023
Topics: Humans; Digoxin; Atrial Fibrillation; Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Heart Rate
PubMed: 37453646
DOI: 10.1016/j.cjca.2023.07.013 -
Cardiovascular Therapeutics Aug 2015Digoxin is the oldest known treatment for heart failure (HF) and has been demonstrated to reduce admissions for worsening heart failure in a large randomized trial... (Review)
Review
BACKGROUND
Digoxin is the oldest known treatment for heart failure (HF) and has been demonstrated to reduce admissions for worsening heart failure in a large randomized trial recruiting patients in sinus rhythm with heart failure and ejection fraction <45%. This study forms the basis for current international guidelines recommending that digoxin should be considered in patients with symptomatic HF despite optimal doses of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and mineralocorticoid receptor antagonists in addition to device therapy, if indicated. However, digoxin predates mortality reducing HF therapies, and this article reviews the historical and recent data.
METHODS
Multiple PubMed searches were performed including, but not limited to, the search terms "digoxin," "heart failure," "efficacy," "treatment," "side-effects," "morbidity," "mortality," and "arrythmia." Articles were excluded if not relevant, not in English or without abstract. Reference lists of relevant articles were manually searched for further references. Due to the large number of articles retrieved, a selection was reviewed based on the authors' best judgement.
RESULTS
Three randomized controlled trials and three large contemporary observational reports of digoxin therapy in heart failure and sinus rhythm were retrieved. Other studies were noted that included patients with heart failure and atrial fibrillation, which were also reviewed.
CONCLUSION
Definitive randomized evidence of digoxin efficacy as add-on therapy in HF is lacking because most landmark trials of modern HF disease modifying agents postdate the randomized studies of digoxin. Furthermore, questions remain regarding the optimum dose of digoxin and there are signals that digoxin may be harmful in some patients with HF. All contemporary data for digoxin in HF are derived from observational studies and the findings are conflicting. Despite two centuries of experience using cardiac glycosides to treat HF, fundamental questions regarding the efficacy and safety of digoxin in HF remain unanswered.
Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiotonic Agents; Digitalis; Digoxin; Heart Failure; Humans; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 25925484
DOI: 10.1111/1755-5922.12130 -
Cardiology Journal 2016There is growing controversy regarding the association between digoxin and mortality in atrial fibrillation (AF). The aim of this analysis was to systematically review... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is growing controversy regarding the association between digoxin and mortality in atrial fibrillation (AF). The aim of this analysis was to systematically review digoxin use and risk of mortality in patients with AF.
METHODS
MEDLINE, EMBASE, GoogleScholar, CINAHL, meeting abstracts, presentations, and Cochrane central databases were searched from inception through December 2014, without language restrictions. For a study to be selected, it had to report the risk of mortality associated with digoxin use in AF patients as an outcome measure. Data were extracted by 2 independent authors. Evidence tables were created.
RESULTS
A total of 16 studies (6 post hoc analyses of randomized controlled trials) with 111,978 digoxin users and 389,643 non-digoxin users were included. In a random effects model, patients treated with digoxin had a 27% increased risk of all-cause mortality (pooled HR 1.27; 95% CI 1.19-1.36) and 21% increased risk of cardiovascular mortality (pooled HR 1.21; 95% CI 1.12-1.30) compared with those who did not use digoxin. In a random effects model, the association of digoxin with all-cause mortality was stronger for AF patients without heart failure (pooled HR 1.47; 95% CI 1.25-1.73) than AF patients with heart failure (pooled HR 1.21; 95% CI 1.07-1.36, interaction p = 0.06).
CONCLUSIONS
Digoxin use in AF is associated with increased risk of all-cause and cardiovascular mortalities. The effect size was larger for AF patients without heart failure than AF patients with heart failure. The study suggests further directed analyses to study the effect that is suggested by this meta-analysis, especially in AF without heart failure.
Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Global Health; Humans; Survival Rate
PubMed: 27064796
DOI: 10.5603/CJ.a2016.0016 -
European Journal of Emergency Medicine... Dec 2023There are currently no universally accepted guidelines for the management of digoxin toxicity. In the absence of clinical practice guidelines, a set of consensus... (Review)
Review
There are currently no universally accepted guidelines for the management of digoxin toxicity. In the absence of clinical practice guidelines, a set of consensus recommendations for management of digoxin toxicity in the clinical setting were developed through a modified Delphi approach. The recommendations highlight the importance of early recognition of signs of potentially life-threatening toxicity that requires immediate treatment with digoxin-specific antibodies. The consensus identifies a straightforward approach to dosing immune antibody fragments according to the presence or absence of signs of life-threatening toxicity. Supportive measures and management of specific signs of toxicity are also covered.
Topics: Humans; Digoxin; Consensus; Drug-Related Side Effects and Adverse Reactions
PubMed: 37650725
DOI: 10.1097/MEJ.0000000000001065 -
Current Pharmaceutical Design 2015The pharmacological treatment of dilated cardiomyopathy overlaps with the treatment of heart failure. The primary objective of this treatment is to slow the progression... (Review)
Review
The pharmacological treatment of dilated cardiomyopathy overlaps with the treatment of heart failure. The primary objective of this treatment is to slow the progression of disease and improve quality and length of life. All patients, including those with asymptomatic dysfunction of the left ventricle, ought to receive angiotensin converting enzyme inhibitors, (in the case of intolerance, angiotensin receptor blockers), and beta blockers. The results of studies involving aliskiren have been, so far, disappointing. In symptomatic heart failure NYHA II-IV diuretics and mineralcorticoid receptor antagonists should be added to treatment. Digoxin is recommended in the event of atrial fibrillation, and otherwise only in the event of NYHA III and IV. Ivabradine is recommended for patients with sinus rhythm and pulse rate of > 70/min. In decompensation of heart failure, dobutamine, phosphodiesterase inhibitors or levosimendan are administered over the short-term. Of the recent treatment options, the vasopressin blocker and adenosine A1 receptor antagonist (rolofylline) were disappointing. One treatment with potential for the future is omecamtiv mecarbil, a heart myosin activator.
Topics: Cardiomyopathy, Dilated; Digoxin; Humans
PubMed: 25483945
DOI: 10.2174/138161282104141204141851 -
Enfermeria Intensiva 2022To identify commonly used intravenous drugs that may produce endothelial damage.
AIMS
To identify commonly used intravenous drugs that may produce endothelial damage.
METHODS
An experimental research study was performed using a sample of 62 intravenous drugs commonly used in emergency care, pH and osmolarity were measured. Subsequently, based on these values, the theoretical capacity to cause irritation or endovascular damage was determined and classified as high, moderate, and low.
RESULTS
Samples from 19 drugs for fluid therapy, 21 antibiotics and 22 drugs for intravenous use were studied. Glucose solutions, sodium bicarbonate 1M and mannitol 10% showed a high capacity to cause venous irritation. Vancomycin, ciprofloxacin, amiodarone, haloperidol, and labetalol solution presented a high capacity for irritation based on their acidic pH. The antibiotics, dexketoprofen, diazepam, digoxin, etomidate, phenytoin, levetiracetam and metamizole also showed high osmotic values in their reconstituted or undiluted presentations. Moreover, osmolarity of diazepam, digoxin and phenytoin remained high despite being diluted in 100 ml of saline.
CONCLUSIONS
Knowing the pH and osmolarity of intravenous drugs allows their capacity to cause endothelial damage to be assessed. The use of comprehensive tables based on the chemical properties of the drugs can be a useful tool to help prevent chemically-induced phlebitis.
Topics: Anti-Bacterial Agents; Diazepam; Digoxin; Humans; Phenytoin; Phlebitis
PubMed: 35941074
DOI: 10.1016/j.enfie.2021.05.003 -
Bulletin of Experimental Biology and... Mar 2023The effects of cardiotonic steroids (ouabain and digoxin) on the bone formation were studied using the organotypic tissue culture in combination with confocal...
The effects of cardiotonic steroids (ouabain and digoxin) on the bone formation were studied using the organotypic tissue culture in combination with confocal microscopy. The expression of α- and α-isoforms of Na,K-ATPase was detected in cells of the bone tissue of 12-day-old chicken embryos. Ouabain in a concentrations 10 M (comparable with its endogenous concentration) can modulate transducer function of Na,K-ATPase and control the growth and proliferation bone tissue cells. Unlike ouabain, digoxin is not involved in the regulation of bone tissue growth in a 12-day-old chicken embryo.
Topics: Animals; Chick Embryo; Ouabain; Sodium-Potassium-Exchanging ATPase; Digoxin; Protein Isoforms; Sodium; Bone Remodeling
PubMed: 37046115
DOI: 10.1007/s10517-023-05768-4 -
Cardiovascular Drugs and Therapy Aug 2023Publishe d decades after several randomized controlled trials (RCT) demonstrating decreased hospitalizations and no effect on all-cause mortality with digoxin use, a... (Review)
Review
PURPOSE
Publishe d decades after several randomized controlled trials (RCT) demonstrating decreased hospitalizations and no effect on all-cause mortality with digoxin use, a series of meta-analyses linking digoxin treatment and mortality have contributed to a narrower application of this medication for the management of heart failure (HF) and atrial fibrillation (AF). Given the conflicting data from the earlier RCTs and more recent meta-analyses, there is a growing polarization among providers for and against the use of digoxin in managing these conditions.
METHODS
To help close this divide, we provide a perspective on the literature with special attention to the quality of both older and more recent studies on this subject.
RESULTS
The data from the highest quality studies we have, RCTs, suggest that digoxin use in patients with HF and/or AF is associated with improvement in several areas of outcomes including functional capacity, symptom management, reduced hospitalizations, fewer deaths due to HF, and treatment of refractory chronic heart failure with rEF, and may even have overall mortality benefit when serum digoxin concentrations are within therapeutic range. These effects are more pronounced in patients with EF < 25% and NYHA Class II-IV and at highest risk for hospitalization.
CONCLUSION
As the risk of confounding factors was minimized by the study design, the likelihood that positive outcomes were identified with digoxin use increased. Clinicians and researchers need further adequately designed and powered RCTs exploring the connection between digoxin therapy and mortality, hospitalizations, and symptom management.
Topics: Humans; Digitalis; Randomized Controlled Trials as Topic; Digoxin; Heart Failure; Atrial Fibrillation
PubMed: 34748147
DOI: 10.1007/s10557-021-07287-8 -
European Heart Journal. Cardiovascular... Jul 2017
Topics: Digoxin; Heart Failure; Humans
PubMed: 28206589
DOI: 10.1093/ehjcvp/pvx004