Digoxin and heart rate
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Digoxin and Heart Rate: A Comprehensive Review
Introduction to Digoxin and Heart Rate Control
Digoxin is a cardiac glycoside commonly used in the management of various heart conditions, including atrial fibrillation (AF) and heart failure. Its primary mechanism involves inhibiting the sodium-potassium ATPase pump, which increases intracellular calcium and enhances cardiac contractility. This article synthesizes recent research on the effects of digoxin on heart rate control, particularly in patients with atrial fibrillation and heart failure.
Digoxin for Atrial Fibrillation and Atrial Flutter
Efficacy in Heart Rate Control
Several studies have evaluated the efficacy of digoxin in controlling heart rate in patients with atrial fibrillation and atrial flutter. A systematic review and meta-analysis of randomized clinical trials found that digoxin significantly reduced heart rate compared to placebo within six hours of treatment onset (mean difference of -12.0 beats per minute)1. However, it was less effective than beta-blockers and calcium antagonists in acute heart rate control1.
Comparison with Other Medications
In a randomized trial comparing intravenous digoxin and placebo, digoxin did not significantly increase the rate of conversion to sinus rhythm but did effectively reduce heart rate within 30 minutes2. Another study comparing digoxin with beta-blockers in patients with permanent AF and heart failure found that digoxin improved systolic function and had fewer adverse events compared to beta-blockers3. However, in the emergency management of acute atrial fibrillation, intravenous diltiazem was found to be superior to digoxin in rapidly controlling ventricular rate7.
Digoxin in Heart Failure with Preserved Ejection Fraction (HFpEF)
Impact on Mortality and Re-admission
The role of digoxin in heart failure, particularly in patients with preserved ejection fraction (HFpEF), remains controversial. An observational study found that digoxin treatment was associated with increased mortality and re-admission rates, especially in patients with lower heart rates9. This suggests that while digoxin may offer some benefits in heart rate control, it may also pose significant risks in certain populations.
Improvement in Cardiac Function
In the RATE-AF trial, digoxin was compared to beta-blockers in patients with permanent AF and heart failure. The study found that digoxin significantly improved multiple parameters of systolic function, including left ventricular ejection fraction and stroke volume, compared to beta-blockers3. This indicates that digoxin may be beneficial in improving cardiac function in patients with heart failure and AF.
Heart Rate Variability and Neurohormonal Modulation
Effects on Heart Rate Variability
Digoxin has also been shown to influence heart rate variability, a marker of autonomic function. In patients with mild to moderate heart failure, digoxin improved heart rate variability and reduced neurohormonal activation, suggesting enhanced cardiac vagal tone6. These effects were more pronounced during daytime hours and in patients with the most impaired baseline heart rate variability.
Conclusion
Digoxin remains a valuable medication for heart rate control in patients with atrial fibrillation and heart failure. It is particularly effective in reducing heart rate compared to placebo and offers some advantages over beta-blockers in improving systolic function. However, its use is associated with increased mortality and re-admission rates in older patients with HFpEF, especially at lower heart rates. Therefore, the decision to use digoxin should be carefully considered, taking into account the patient's overall health status and specific clinical circumstances. Further research is needed to fully understand the long-term effects and optimal use of digoxin in various patient populations.
Sources and full results
Most relevant research papers on this topic
Digoxin for atrial fibrillation and atrial flutter: A systematic review with meta-analysis and trial sequential analysis of randomised clinical trials
Digoxin is a safe and effective treatment for atrial fibrillation and atrial flutter, but its long-term safety and effectiveness remain unclear.
Meta-Analysis
Rigorous JournalConversion of atrial fibrillation to sinus rhythm and rate control by digoxin in comparison to placebo.
Intravenous digoxin offers no substantial advantages over placebo in converting recent onset atrial fibrillation to sinus rhythm and provides weak rate control.
RCT
Highly CitedDigoxin improves systolic cardiac function in patients with AF and HFpEF: the RATE-AF randomised trial
Digoxin improves systolic cardiac function in patients with permanent atrial fibrillation and heart failure, but not diastolic function, compared to beta-blockers.
RCTRigorous JournalIntravenous digoxin in acute atrial fibrillation. Results of a randomized, placebo-controlled multicentre trial in 239 patients. The Digitalis in Acute Atrial Fibrillation (DAAF) Trial Group.
Intravenous digoxin does not increase the rate of conversion to sinus rhythm in acute atrial fibrillation, but has a fast acting and significant effect on heart rate and remains an alternative in haemodynamically stable patients.
RCTDigoxin or verapamil or metoprolol for heart rate control in patients with mitral stenosis--a randomised cross-over study.
Digoxin, metoprolol, and verapamil show similar effectiveness in controlling heart rate in patients with mitral stenosis, with the degree of improvement depending on the drug's ability to control resting and exercise heart rates.
RCTHEART-RATE-VARIABILITY IN PATIENTS WITH MILD-TO-MODERATE HEART-FAILURE - EFFECTS OF NEUROHORMONAL MODULATION BY DIGOXIN AND IBOPAMINE
Digoxin may prevent progressive deterioration in heart rate variability in patients with early stages of heart failure, while ibopamine shows no significant effects.
RCTEmergency management of atrial fibrillation and flutter: intravenous diltiazem versus intravenous digoxin.
Intravenous diltiazem significantly decreases ventricular heart rate within 5 minutes, while i.v. digoxin takes 3 hours, and a combination of diltiazem and digoxin shows no advantage within 3 hours.
RCTHighly CitedEffect of Digoxin vs Bisoprolol for Heart Rate Control in Atrial Fibrillation on Patient-Reported Quality of Life: The RATE-AF Randomized Clinical Trial.
Low-dose digoxin and bisoprolol show no significant difference in patient-reported quality of life for patients with permanent atrial fibrillation and coexisting heart failure.
RCTHighly CitedDigoxin and prognosis of heart failure in older patients with preserved ejection fraction: Importance of heart rate. Results from an observational and multicenter study.
Digoxin treatment in older patients with preserved ejection fraction after acute heart failure is associated with increased mortality and re-admission, particularly in those with lower heart rates.
Observational StudyUrgent management of rapid heart rate in patients with atrial fibrillation/flutter and left ventricular dysfunction: comparison of the ultra-short-acting β1-selective blocker landiolol with digoxin (J-Land Study).
Landiolol is more effective for controlling rapid heart rate than digoxin in patients with atrial fibrillation/flutter and left ventricular dysfunction.
RCTHighly Cited