Table 1 - uploaded by Naqash Sethi
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Background
Atrial fibrillation is the most common arrhythmia of the heart with a prevalence of approximately 2% in the western world. Atrial flutter, another arrhythmia, occurs less often with an incidence of approximately 200,000 new patients per year in the USA. Patients with atrial fibrillation and atrial flutter have an increased risk of death...
Context in source publication
Context 1
... on the mechanism, the drugs are divided into either anticoagulants or antiplatelet drugs. The classifi- cation, mechanism, and examples of anticoagulants and antiplatelet drugs are summarised in Table 1. The comparative efficacy and safety between anticoag- ulants and antiplatelet drugs has been assessed. ...
Citations
... I 2 =17%). Also, they compared digoxin with placebo and reported that digoxin was superior to placebo in controlling the heart rate both within 6 and 6-24 hours, but inferior to beta blockers(37). In 2019, a meta-analysis of 38 trials and 825.061 ...
Background:
Digoxin is a cardiac glycoside, derived from the plant Digitalis purpurea. For many years digitalis has been widely used in the treatment of heart failure (HF), owing to its cardiotonic and neurohormonal effects and atrial fibrillation (AF), due to its parasympathomimetic effect on the AV node.
Objective:
The aim of this paper is to evaluate the available evidence on the safety and efficacy of digoxin in patients with HF and AF, by reviewing the pertinent literature.
Methods:
We conducted a PubMed/MEDLINE and SCOPUS search to evaluate the currently available evidence on the administration of digoxin and its association with all-cause mortality risk in patients with AF and HF.
Results:
Several observational analyses of clinical trials and meta-analyses have shown conflicting results on the safety and efficacy of digoxin administration in patients with AF and HF. According to these results, digoxin should be avoided in patients without HF, as it is associated with worse outcomes. On the other hand, in patients with AF and HF digoxin should be used with caution.
Conclusion:
The impact of digoxin on all-cause mortality and adverse effects in these patients remains unclear based on the current evidence. More trials at low risk of bias evaluating the effects of digoxin are needed.
... [589][590][591][592] However, a recent meta-analysis of 28 trials of digoxin for AF rate control showed no increase in all-cause mortality vs control intervention (RR, 0.82; 95% CI, 0.24-11.5). 593 As such, digoxin remains a reasonable choice for selected older or sedentary patients with HF and for those with inadequate rate control while receiving maximally tolerated doses of a b-blocker/ND-CCB. Although there is no direct evidence to support digoxin concentration monitoring for AF rate control, it might be reasonable to monitor patients at risk of digoxin-related adverse events (eg, female sex with low body weight and impaired renal function), at the clinician's discretion, aiming for trough levels between 0.5 and 0.9 ng/mL. ...
The Canadian Cardiovascular Society (CCS) atrial fibrillation (AF) guidelines program was developed to aid clinicians in the management of these complex patients, as well as to provide direction to policy makers and health care systems regarding related issues. The most recent comprehensive CCS AF guidelines update was published in 2010. Since then, periodic updates were published dealing with rapidly changing areas. However, by 2020 a large number of developments had accumulated in a wide range of areas, motivating the committee to create a complete guideline review. The 2020 iteration of the CCS AF guidelines represents a comprehensive renewal that integrates, updates, and replaces the past decade of guidelines, recommendations, and practical tips. It is intended to be used by practicing clinicians across all disciplines who care for patients with AF. The Grading of Recommendations, Assessment, Development and Evaluations system was used to grade recommendation strength and the quality of evidence. Areas of focus include: AF classification and definitions, epidemiology, pathophysiology, clinical evaluation, screening and opportunistic AF detection, detection and management of modifiable risk factors, integrated approach to AF management, stroke prevention, arrhythmia management, sex differences, and AF in special populations. Extensive use is made of tables and figures to synthesize important material and present key concepts. This document should be an important aid for knowledge translation and a tool to help improve clinical management of this important and challenging arrhythmia.
... We conducted this systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA) (S1 Text) [23], and the updated Cochrane methodology used in this systematic review is described in detail in our protocol (S2 Text) [24][25][26], which was registered prior to the systematic literature search. ...
... If there was substantial discrepancy between the results of the two methods, we reported and discussed the results [36]. We used Trial Sequential Analysis (TSA) to control for random errors by estimating the diversity-adjusted required information size (DARIS) (that is the number of participants needed in a meta-analysis to detect or reject a certain intervention effect) [24,25,36,[39][40][41][42][43][44][45][46][47][48]. The DARIS is based on our predefined anticipated intervention effect. ...
... When analysing dichotomous outcomes, we pragmatically anticipated an intervention effect of 15% risk ratio reduction (RRR). When analysing continuous outcomes, we pragmatically anticipated an intervention effect equal to the MD of the observed standard difference (SD)/2 [25,49]. Based on the DARIS, trial sequential monitoring boundaries were constructed. ...
Background
During recent years, systematic reviews of observational studies have compared digoxin to no digoxin in patients with atrial fibrillation or atrial flutter, and the results of these reviews suggested that digoxin seems to increase the risk of all-cause mortality regardless of concomitant heart failure. Our objective was to assess the benefits and harms of digoxin for atrial fibrillation and atrial flutter based on randomized clinical trials.
Methods
We searched CENTRAL, MEDLINE, Embase, LILACS, SCI-Expanded, BIOSIS for eligible trials comparing digoxin versus placebo, no intervention, or other medical interventions in patients with atrial fibrillation or atrial flutter in October 2016. Our primary outcomes were all-cause mortality, serious adverse events, and quality of life. Our secondary outcomes were heart failure, stroke, heart rate control, and conversion to sinus rhythm. We performed both random-effects and fixed-effect meta-analyses and chose the more conservative result as our primary result. We used Trial Sequential Analysis (TSA) to control for random errors. We used GRADE to assess the quality of the body of evidence.
Results
28 trials (n = 2223 participants) were included. All were at high risk of bias and reported only short-term follow-up. When digoxin was compared with all control interventions in one analysis, we found no evidence of a difference on all-cause mortality (risk ratio (RR), 0.82; TSA-adjusted confidence interval (CI), 0.02 to 31.2; I² = 0%); serious adverse events (RR, 1.65; TSA-adjusted CI, 0.24 to 11.5; I² = 0%); quality of life; heart failure (RR, 1.05; TSA-adjusted CI, 0.00 to 1141.8; I² = 51%); and stroke (RR, 2.27; TSA-adjusted CI, 0.00 to 7887.3; I² = 17%). Our analyses on acute heart rate control (within 6 hours of treatment onset) showed firm evidence of digoxin being superior compared with placebo (mean difference (MD), -12.0 beats per minute (bpm); TSA-adjusted CI, -17.2 to -6.76; I² = 0%) and inferior compared with beta blockers (MD, 20.7 bpm; TSA-adjusted CI, 14.2 to 27.2; I² = 0%). Meta-analyses on acute heart rate control showed that digoxin was inferior compared with both calcium antagonists (MD, 21.0 bpm; TSA-adjusted CI, -30.3 to 72.3) and with amiodarone (MD, 14.7 bpm; TSA-adjusted CI, -0.58 to 30.0; I² = 42%), but in both comparisons TSAs showed that we lacked information. Meta-analysis on acute conversion to sinus rhythm showed that digoxin compared with amiodarone reduced the probability of converting atrial fibrillation to sinus rhythm, but TSA showed that we lacked information (RR, 0.54; TSA-adjusted CI, 0.13 to 2.21; I² = 0%).
Conclusions
The clinical effects of digoxin on all-cause mortality, serious adverse events, quality of life, heart failure, and stroke are unclear based on current evidence. Digoxin seems to be superior compared with placebo in reducing the heart rate, but inferior compared with beta blockers. The long-term effect of digoxin is unclear, as no trials reported long-term follow-up. More trials at low risk of bias and low risk of random errors assessing the clinical effects of digoxin are needed.
Systematic review registration
PROSPERO CRD42016052935
... For example, in some recent trials of stroke prevention involving patients with atrial fibrillation, rates of digoxin use ranged from 29% to 39%. 10,11 Another meta-analysis on this topic is being planned, 12 but the results will be subject to the limitations of the existing publications. A randomized controlled trial on the effect of digoxin on all-cause mortality in patients who have atrial fibrillation with or without HFrEF (most urgently the latter) would provide better information. ...
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.
