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Contraception: X 2020Clinicians have used feticidal agents prior to second trimester abortion for many years. Despite the widespread use of various agents to induce fetal demise, a...
UNLABELLED
Clinicians have used feticidal agents prior to second trimester abortion for many years. Despite the widespread use of various agents to induce fetal demise, a comprehensive or systematic review of the evidence is lacking on the safety, effectiveness, and most effective routes of administration.
OBJECTIVES
To evaluate the existing drugs and routes of administration used in inducing fetal demise prior to abortion, and to determine the safety, effectiveness, and acceptability of these feticidal agents.
METHODS
We searched PubMed, EMBASE, CINAHL, POPLINE, and Global Index Medicus to identify studies describing pharmacologic agents used to induce fetal demise prior to termination of pregnancy. We included randomized controlled trials and observational studies comparing digoxin, potassium chloride (KCL), and lidocaine to induce fetal demise. We included studies that evaluated the primary outcomes of safety and effectiveness, including success in achieving fetal demise, induction to expulsion time for medical abortion, dilation and evacuation time, as well as maternal side effects and complications. Two authors independently screened abstracts and full texts. One reviewer extracted data from the included studies, which was counterchecked by a second reviewer.
RESULTS
We identified eight studies that met inclusion criteria: three randomized controlled trials, and five observational studies. A total of 4505 women received drugs to induce fetal demise at 17 to 38 weeks' gestation, including digoxin ( = 4174), KCL ( = 324), and lidocaine ( = 7). Intra-fetal digoxin was superior to intra-amniotic digoxin in achieving fetal demise (OR 3.51, 95% CI 1.60, 7.78). Intracardiac KCL 15% 2-3 mL reduced induction to expulsion time by 320 min (p <.006).Similarly, intracardiac KCL 15% 1-3 ml reduced dilation and evacuation time from 16.1 ± 7.9 min to 12.7 ± 5 min (p < 0.001). Intracardiac lidocaine 2% 10 mL was more effective at achieving fetal demise than intracardiac KCL 6 mmol (85.7% vs. 57.9%). Intra-amniotic and intra-fetal digoxin 1 mg, as compared to no feticidal agent, led to greater pre-procedure expulsion, hospital readmission, and the presence of one or more signs of infection.
CONCLUSIONS
Evidence from included cohort studies demonstrates that digoxin, KCL, and lidocaine are all effective in inducing fetal demise. Intra-fetal administration of digoxin is superior to intra-amniotic digoxin administration. Administration of feticide using intracardiac KCL may shorten the abortion experience. Limited data from observational studies also supports an increase in maternal side effects and/or complications related to the administration of digoxin.
IMPLICATIONS
Intra-fetal administration of digoxin is more effective in achieving fetal demise when compared to intra-amniotic administration. There is a knowledge gap in determining the single best drug for inducing fetal demise prior to abortion. Additional research is needed to compare different feticidal agents in terms of safety and effectiveness.
PubMed: 33294839
DOI: 10.1016/j.conx.2020.100046 -
American Journal of Obstetrics and... Feb 2022There has been increasing research momentum to identify new therapeutic agents for the prevention or treatment of preeclampsia, drugs that can affect the underlying...
There has been increasing research momentum to identify new therapeutic agents for the prevention or treatment of preeclampsia, drugs that can affect the underlying disease pathophysiology. Molecular targets of candidate treatments include oxidative stress, antiangiogenic factors, and the angiotensin, nitric oxide, and proinflammatory pathways. The proposed treatments undergoing preclinical and clinical trial evaluation are thought to act on placental or endothelial disease or both. Most have adopted the pragmatic strategy of repurposing drugs. Of all the therapeutic agents proposed, pravastatin has received the most interest. There are preclinical studies showing that it has pleiotropic actions that favorably impact on multiple molecular targets and can resolve a preeclampsia phenotype in many animal models. An early phase clinical trial suggests that it may have therapeutic activity. Several large prevention trials are planned or ongoing and, when completed, could definitively address whether pravastatin can prevent preeclampsia. Proton-pump inhibitors, metformin, and sulfasalazine are other drugs with preclinical evidence of multiple molecular actions that could resolve the pathophysiology of preeclampsia. These agents are also currently being evaluated in clinical trials. There have been many recent preclinical studies identifying the potential of numerous natural compounds to treat preeclampsia, such as plant extracts and micronutrients that have potent anti-inflammatory or antioxidant activity. Recent preclinical studies have also proposed novel molecular-targeted strategies, such as monoclonal antibodies targeting tumor necrosis factor alpha, placental growth factor, and short interfering RNA technology, to silence the gene expression of soluble fms-like tyrosine kinase-1 or angiotensinogen. Other treatment approaches that have transitioned to human trials (ranging from single-arm to phase III trials that have been completed or are ongoing) include folic acid, nitric oxide donors (such as L-arginine), recombinant antithrombin III, digoxin immune antigen-binding fragment, and melatonin. There have been case series showing the removal of circulating soluble fms-like tyrosine kinase-1 may help stabilize the disease and prolong pregnancy. Interestingly, there are case reports suggesting that monoclonal antibody eculizumab (complement inhibitor) may have therapeutic potential. If new agents are discovered that are proven to be effective in preventing or treating preeclampsia, the potential to improve global maternal and perinatal health will be significant.
Topics: Antibodies, Monoclonal; Antioxidants; Antithrombin III; Biological Products; Blood Component Removal; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Metformin; Micronutrients; Placenta Growth Factor; Plant Extracts; Pravastatin; Pre-Eclampsia; Pregnancy; Proton Pump Inhibitors; RNA, Small Interfering; Recombinant Proteins; Sulfasalazine; Vascular Endothelial Growth Factor Receptor-1
PubMed: 32946849
DOI: 10.1016/j.ajog.2020.09.014 -
British Journal of Clinical Pharmacology Jul 2020This is a PROSPERO registered systematic review (CRD42018105207), conducted to summarize the available knowledge regarding the population pharmacokinetics of digoxin in... (Review)
Review
This is a PROSPERO registered systematic review (CRD42018105207), conducted to summarize the available knowledge regarding the population pharmacokinetics of digoxin in paediatrics and to identify the sources of variability in its disposition. PubMed, ISI Web of Science, SCOPUS and Science Direct databases were searched from inception to January 2019. All paediatric population pharmacokinetic studies of digoxin that utilized the nonlinear mixed-effect modelling approach were incorporated in this review, and data were synthesized descriptively. After application of the inclusion-exclusion criteria 8 studies were included. Most studies described digoxin pharmacokinetics as a 1-compartment model with only 1 study describing its pharmacokinetics as 2-compartments. Age was an important predictor of clearance in studies involving neonates or infants, other predictors of clearance were weight, height, serum creatinine, coadministration of spironolactone and presence of congestive heart failure. Congestive heart failure was also associated with an increased volume of distribution in 1 study. The estimated value of apparent clearance in a typical individual standardized by mean weight ranged between 0.24 and 0.56 L/h/kg, the interindividual variability in clearance ranged between 7.0 and 35.1%. Half of the studies evaluated the performance of their developed models via external evaluation. In conclusion, substantial predictors of digoxin pharmacokinetics in the paediatric population in addition to model characteristics and evaluation techniques are presented. For clinicians, clearance could be predicted using age especially in neonates or infants, weight, height, serum creatinine, coadministration of medications and disease status. For future researchers, designing pharmacokinetic studies that allow 2-compartment modelling and linking pharmacokinetics with pharmacodynamics is recommended.
Topics: Child; Digoxin; Heart Failure; Humans; Infant; Infant, Newborn; Models, Biological; Nonlinear Dynamics; Pediatrics; Spironolactone
PubMed: 32153059
DOI: 10.1111/bcp.14272 -
The Cochrane Database of Systematic... Feb 2020Approximately half of people with heart failure have chronic kidney disease (CKD). Pharmacological interventions for heart failure in people with CKD have the potential... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Approximately half of people with heart failure have chronic kidney disease (CKD). Pharmacological interventions for heart failure in people with CKD have the potential to reduce death (any cause) or hospitalisations for decompensated heart failure. However, these interventions are of uncertain benefit and may increase the risk of harm, such as hypotension and electrolyte abnormalities, in those with CKD.
OBJECTIVES
This review aims to look at the benefits and harms of pharmacological interventions for HF (i.e., antihypertensive agents, inotropes, and agents that may improve the heart performance indirectly) in people with HF and CKD.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies through 12 September 2019 in consultation with an Information Specialist and using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
We included randomised controlled trials of any pharmacological intervention for acute or chronic heart failure, among people of any age with chronic kidney disease of at least three months duration.
DATA COLLECTION AND ANALYSIS
Two authors independently screened the records to identify eligible studies and extracted data on the following dichotomous outcomes: death, hospitalisations, worsening heart failure, worsening kidney function, hyperkalaemia, and hypotension. We used random effects meta-analysis to estimate treatment effects, which we expressed as a risk ratio (RR) with 95% confidence intervals (CI). We assessed the risk of bias using the Cochrane tool. We applied the GRADE methodology to rate the certainty of evidence.
MAIN RESULTS
One hundred and twelve studies met our selection criteria: 15 were studies of adults with CKD; 16 studies were conducted in the general population but provided subgroup data for people with CKD; and 81 studies included individuals with CKD, however, data for this subgroup were not provided. The risk of bias in all 112 studies was frequently high or unclear. Of the 31 studies (23,762 participants) with data on CKD patients, follow-up ranged from three months to five years, and study size ranged from 16 to 2916 participants. In total, 26 studies (19,612 participants) reported disaggregated and extractable data on at least one outcome of interest for our review and were included in our meta-analyses. In acute heart failure, the effects of adenosine A1-receptor antagonists, dopamine, nesiritide, or serelaxin on death, hospitalisations, worsening heart failure or kidney function, hyperkalaemia, hypotension or quality of life were uncertain due to sparse data or were not reported. In chronic heart failure, the effects of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) (4 studies, 5003 participants: RR 0.85, 95% CI 0.70 to 1.02; I = 78%; low certainty evidence), aldosterone antagonists (2 studies, 34 participants: RR 0.61 95% CI 0.06 to 6.59; very low certainty evidence), and vasopressin receptor antagonists (RR 1.26, 95% CI 0.55 to 2.89; 2 studies, 1840 participants; low certainty evidence) on death (any cause) were uncertain. Treatment with beta-blockers may reduce the risk of death (any cause) (4 studies, 3136 participants: RR 0.69, 95% CI 0.60 to 0.79; I = 0%; moderate certainty evidence). Treatment with ACEi or ARB (2 studies, 1368 participants: RR 0.90, 95% CI 0.43 to 1.90; I = 97%; very low certainty evidence) had uncertain effects on hospitalisation for heart failure, as treatment estimates were consistent with either benefit or harm. Treatment with beta-blockers may decrease hospitalisation for heart failure (3 studies, 2287 participants: RR 0.67, 95% CI 0.43 to 1.05; I = 87%; low certainty evidence). Aldosterone antagonists may increase the risk of hyperkalaemia compared to placebo or no treatment (3 studies, 826 participants: RR 2.91, 95% CI 2.03 to 4.17; I = 0%; low certainty evidence). Renin inhibitors had uncertain risks of hyperkalaemia (2 studies, 142 participants: RR 0.86, 95% CI 0.49 to 1.49; I = 0%; very low certainty). We were unable to estimate whether treatment with sinus node inhibitors affects the risk of hyperkalaemia, as there were few studies and meta-analysis was not possible. Hyperkalaemia was not reported for the CKD subgroup in studies investigating other therapies. The effects of ACEi or ARB, or aldosterone antagonists on worsening heart failure or kidney function, hypotension, or quality of life were uncertain due to sparse data or were not reported. Effects of anti-arrhythmic agents, digoxin, phosphodiesterase inhibitors, renin inhibitors, sinus node inhibitors, vasodilators, and vasopressin receptor antagonists were very uncertain due to the paucity of studies.
AUTHORS' CONCLUSIONS
The effects of pharmacological interventions for heart failure in people with CKD are uncertain and there is insufficient evidence to inform clinical practice. Study data for treatment outcomes in patients with heart failure and CKD are sparse despite the potential impact of kidney impairment on the benefits and harms of treatment. Future research aimed at analysing existing data in general population HF studies to explore the effect in subgroups of patients with CKD, considering stage of disease, may yield valuable insights for the management of people with HF and CKD.
Topics: Adrenergic beta-Antagonists; Antidiuretic Hormone Receptor Antagonists; Antihypertensive Agents; Heart Failure; Hospitalization; Humans; Mineralocorticoid Receptor Antagonists; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic
PubMed: 32103487
DOI: 10.1002/14651858.CD012466.pub2 -
Evidence-based Complementary and... 2019Heart failure is a major public health problem worldwide nowadays. However, the morbidity, mortality, and awareness of heart failure are not satisfied as well as the... (Review)
Review
Efficacy and Safety of Fuzi Formulae on the Treatment of Heart Failure as Complementary Therapy: A Systematic Review and Meta-Analysis of High-Quality Randomized Controlled Trials.
OBJECTIVE
Heart failure is a major public health problem worldwide nowadays. However, the morbidity, mortality, and awareness of heart failure are not satisfied as well as the status of current treatments. According to the standard treatment for chronic heart failure (CHFST), Fuzi (the seminal root of Debx.) formulae are widely used as a complementary treatment for heart failure in clinical practice for a long time. We are aiming to assess the efficacy and safety of Fuzi formulae (FZF) on the treatment of heart failure according to high-quality randomized controlled trials (RCTs).
METHODS
RCTs in PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang Database were searched from their inception until June 2019. In addition, the U.S. National Library of Medicine (clinicaltrials.gov) and the Chinese Clinical Trial Registry (http://www.chictr.org.cn) were also searched. We included RCTs that test the efficacy and safety of FZF for the treatment of heart failure, compared with placebo, CHFST, or placebo plus CHFST. The methodological quality of included studies were evaluated by the Cochrane Collaboration's tool for assessing risk of bias. RCTs with Cochrane risk of bias (RoB) score ≥4 were included in the analysis. The meta-analysis was conducted through RevMan 5.2 software. The GRADE approach was used to assess the quality of the evidence.
RESULTS
Twelve RCTs with 1490 participants were identified. The studies investigated the efficacy and safety of FZF, such as FZF plus the CHFST vs placebo plus CHFST ( = 4), FZF plus CHFST vs CHFST ( = 6), FZF plus digoxin tablets (DT) plus CHFST vs placebo plus DT plus CHFST ( = 1), and FZF plus placebo plus CHFST vs placebo plus DT plus CHFST ( = 1). Meta-analysis indicated that FZF have additional benefits based on the CHFST in reducing plasma NT-proBNP level, MLHFQ scores, Lee's heart failure scores (LHFs), and composite cardiac events (CCEs). Meanwhile, it also improved the efficacy on TCM symptoms (TCMs), NYHA functional classification (NYHAfc), 6MWD, and LVEF. Adverse events were reported in 6 out of 12 studies without significant statistical difference. However, after assessing the strength of evidence, it was found that only the quality of evidence for CCEs was high, and the others were either moderate or low or very low. So we could not draw confirmative conclusions on its additional benefits except CCEs. Further clinical trials should be well designed to avoid the issues that were identified in this study.
CONCLUSION
The efficacy and additional benefits of FZF for CCEs were certain according to the high-quality evidence assessed through GRADE. However, the efficacy and additional benefits for the other outcomes were uncertain judging from current studies. In addition, the safety assessment has a great room for improvement. Thus, further research studies are needed to find more convincing proofs.
PubMed: 31949473
DOI: 10.1155/2019/9728957 -
The Annals of Thoracic Surgery Apr 2020Two quality measures used in public reporting and value-based payment programs require β-blockers be administered less than 24 hours before isolated coronary artery...
BACKGROUND
Two quality measures used in public reporting and value-based payment programs require β-blockers be administered less than 24 hours before isolated coronary artery bypass graft surgery to prevent atrial fibrillation and mortality. Questions have arisen about continued use of these measures.
METHODS
We conducted a systematic search for randomized controlled trials (RCTs) examining the impact of preoperative β-blockers on atrial fibrillation or mortality after isolated coronary artery bypass graft surgery to determine what evidence of efficacy supports the measures.
RESULTS
We identified 11 RCTs. All continued β-blockers postoperatively, making it unfeasible to separate the benefits of preoperative vs postoperative administration. Meta-analysis was precluded by methodologic variation in β-blocker utilized, timing and dosage, and supplemental and comparison treatments. Of the eight comparisons of β-blockers/β-blocker plus digoxin versus placebo (n = 826 patients), six showed significant reductions in atrial fibrillation/supraventricular arrhythmias. Of the three comparisons (n = 444) of β-blockers versus amiodarone, two found no significant difference in atrial fibrillation; the third showed significantly lower incidence with amiodarone. One RCT compared β-blocker plus amiodarone versus each of those drugs separately; the combination reduced atrial fibrillation significantly better than the β-blocker alone, but not amiodarone alone. Seven RCTs reported short-term mortality, but this outcome was too rare and the sample sizes too small to provide any meaningful comparisons.
CONCLUSIONS
Existing RCT evidence does not support the structure of quality measures that require β-blocker administration specifically within 24 hours before coronary artery bypass graft surgery to prevent postoperative atrial fibrillation or short-term mortality. Quality measures should be revised to align with the evidence, and further studies conducted to determine optimal timing and method of prophylaxis.
Topics: Adrenergic beta-Antagonists; Atrial Fibrillation; Coronary Artery Bypass; Coronary Artery Disease; Global Health; Humans; Incidence; Postoperative Complications; Preoperative Care; Quality Indicators, Health Care; Survival Rate
PubMed: 31513778
DOI: 10.1016/j.athoracsur.2019.07.056 -
JACC. Heart Failure Mar 2019This study sought to summarize all available evidence on sex differences in adverse drug reactions (ADRs) to heart failure (HF) medication.
OBJECTIVES
This study sought to summarize all available evidence on sex differences in adverse drug reactions (ADRs) to heart failure (HF) medication.
BACKGROUND
Women are more likely to experience ADRs than men, and these reactions may negatively affect women's immediate and long-term health. HF in particular is associated with increased ADR risk because of the high number of comorbidities and older age. However, little is known about ADRs in women with HF who are treated with guideline-recommended drugs.
METHODS
A systematic search of PubMed and EMBASE was performed to collect all available information on ADRs to angiotensin-converting enzyme inhibitors, β-blockers, angiotensin II receptor blockers, mineralocorticoid receptor antagonists, ivabradine, and digoxin in both women and men with HF.
RESULTS
The search identified 155 eligible records, of which only 11 (7%) reported ADR data for women and men separately. Sex-stratified reporting of ADRs did not increase over the last decades. Six of the 11 studies did not report sex differences. Three studies reported a higher risk of angiotensin-converting enzyme inhibitor-related ADRs in women, 1 study showed higher digoxin-related mortality risk for women, and 1 study reported a higher risk of mineralocorticoid receptor antagonist-related ADRs in men. No sex differences in ADRs were reported for angiotensin II receptor blockers and β-blockers. Sex-stratified data were not available for ivabradine.
CONCLUSIONS
These results underline the scarcity of ADR data stratified by sex. The study investigators call for a change in standard scientific practice toward reporting of ADR data for women and men separately.
Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Cardiovascular Agents; Digoxin; Drug-Related Side Effects and Adverse Reactions; Female; Heart Failure; Humans; Ivabradine; Male; Mineralocorticoid Receptor Antagonists; Mortality; Practice Guidelines as Topic; Research Design; Research Report; Sex Distribution; Sex Factors; Stroke Volume
PubMed: 30819382
DOI: 10.1016/j.jchf.2019.01.009 -
Journal of Women's Health (2002) May 2019Cardiovascular disease is now the leading cause of pregnancy-related deaths in the United States. Increasing maternal mortality in the United States underscores the...
Cardiovascular disease is now the leading cause of pregnancy-related deaths in the United States. Increasing maternal mortality in the United States underscores the importance of proper cardiovascular management. Significant physiological changes during pregnancy affect the heart's ability to respond to pathological processes such as hypertension and heart failure. These physiological changes further affect the pharmacokinetic and pharmacodynamic properties of cardiac medications. During pregnancy, these changes can significantly alter medication efficacy and metabolism. This article systematically reviews the literature on safety, efficacy, pharmacokinetics, and pharmacodynamics of cardiovascular drugs used for hypertension and heart failure during pregnancy and lactation. The 2017 American College of Cardiology/American Heart Association hypertension guidelines recommend transitioning pregnant patients to methyldopa, nifedipine, or labetalol. Heart failure medications, including beta-blockers, furosemide, and digoxin, are relatively safe and can be used effectively. Medications that block the renin angiotensin-aldosterone system have been shown to be beneficial in the general population; however, they are teratogenic and, therefore, contraindicated in pregnancy. Cardiovascular medications can also enter breast milk and, therefore, care must be taken when selecting drugs during the lactation period. A summary of the safety of drugs during pregnancy and lactation from an online resource, LactMed by the National Library of Medicine's TOXNET database, is included. High-risk pregnant patients with cardiovascular disease require a multispecialty team of doctors, including health care providers from obstetrics and gynecology, maternal fetal medicine, internal medicine, cardiovascular disease specialists, and specialized pharmacology expertise.
Topics: Breast Feeding; Cardiovascular Agents; Female; Heart Failure; Humans; Hypertension; Pregnancy; Pregnancy Complications, Cardiovascular; United States
PubMed: 30407107
DOI: 10.1089/jwh.2018.7145 -
European Heart Journal Oct 2018Treatment 'effects' are often inferred from non-randomized and observational studies. These studies have inherent biases and limitations, which may make therapeutic... (Meta-Analysis)
Meta-Analysis
AIMS
Treatment 'effects' are often inferred from non-randomized and observational studies. These studies have inherent biases and limitations, which may make therapeutic inferences based on their results unreliable. We compared the conflicting findings of these studies to those of prospective randomized controlled trials (RCTs) in relation to pharmacological treatments for heart failure (HF).
METHODS AND RESULTS
We searched Medline and Embase to identify studies of the association between non-randomized drug therapy and all-cause mortality in patients with HF until 31 December 2017. The treatments of interest were: angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, mineralocorticoid receptor antagonists (MRAs), statins, and digoxin. We compared the findings of these observational studies with those of relevant RCTs. We identified 92 publications, reporting 94 non-randomized studies, describing 158 estimates of the 'effect' of the six treatments of interest on all-cause mortality, i.e. some studies examined more than one treatment and/or HF phenotype. These six treatments had been tested in 25 RCTs. For example, two pivotal RCTs showed that MRAs reduced mortality in patients with HF with reduced ejection fraction. However, only one of 12 non-randomized studies found that MRAs were of benefit, with 10 finding a neutral effect, and one a harmful effect.
CONCLUSION
This comprehensive comparison of studies of non-randomized data with the findings of RCTs in HF shows that it is not possible to make reliable therapeutic inferences from observational associations. While trials undoubtedly leave gaps in evidence and enrol selected participants, they clearly remain the best guide to the treatment of patients.
Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Causality; Confounding Factors, Epidemiologic; Female; Heart Failure; Humans; Male; Middle Aged; Observational Studies as Topic
PubMed: 30085087
DOI: 10.1093/eurheartj/ehy407 -
American Journal of Cardiovascular... Dec 2018The history of digitalis is rich and interesting, with the first use usually attributed to William Withering and his study on the foxglove published in 1785. However,...
The history of digitalis is rich and interesting, with the first use usually attributed to William Withering and his study on the foxglove published in 1785. However, some knowledge of plants with digitalis-like effects used for congestive heart failure (CHF) was in evidence as early as Roman times. The active components of the foxglove (Digitalis purpurea and Digitalis lanata) are classified as cardiac glycosides or cardiotonic steroids and include the well-known digitalis leaf, digitoxin, and digoxin; ouabain is a rapid-acting glycoside usually obtained from Strophanthus gratus. These drugs are potent inhibitors of cellular membrane sodium-potassium adenosine triphosphatase (Na/K-ATPase). For most of the twentieth century, digitalis and its derivatives, especially digoxin, were the available standard of care for CHF. However, as the century closed, many doubts, especially regarding safety, were raised about their use as other treatments for CHF, such as decreasing the preload of the left ventricle, were developed. Careful attention is needed to maintain the serum digoxin level at ≤ 1.0 ng/ml because of the very narrow therapeutic window of the medication. Evidence for benefit exists for CHF with reduced ejection fraction (EF), also referred to as heart failure with reduced EF (HFrEF), especially when considering the combination of mortality, morbidity, and decreased hospitalizations. However, the major support for using digoxin is in atrial fibrillation (AF) with a rapid ventricular response when a rate control approach is planned. The strongest support of all for digoxin is for its use in rate control in AF in the presence of a marginal blood pressure, since all other rate control medications contribute to additional hypotension. In summary, these days, digoxin appears to be of most use in HFrEF and in AF with rapid ventricular response for rate control, especially when associated with hypotension. The valuable history of the foxglove continues; it has been modified but not relegated to the garden or the medical history book, as some would advocate.
Topics: Age Factors; Atrial Fibrillation; Body Weight; Cardiotonic Agents; Digitalis; Digitalis Glycosides; Digoxin; Drug Interactions; Drug Monitoring; Heart Failure; Humans; Meta-Analysis as Topic; Neoplasms; Observational Studies as Topic; Ouabain; Plant Extracts; Randomized Controlled Trials as Topic; Renal Insufficiency; ST Elevation Myocardial Infarction; Sex Factors; Sodium-Potassium-Exchanging ATPase; Stroke Volume
PubMed: 30066080
DOI: 10.1007/s40256-018-0292-1