Question explored with the scientific record
Conversation so far
- 1 What if Digoxin was used for years and then stopped without replacing it
- 2 The digoxin was prescibed due to atrial fibrillation (a fast, irregular heartbeat).
Answered on this page ↓
The digoxin was prescibed due to atrial fibrillation (a fast, irregular heartbeat).
The short version: stopping digoxin in atrial fibrillation without replacing it with a better rate-control drug is less risky than stopping it in heart failure, but the evidence shows digoxin itself is linked to higher mortality and should not have been a long-term drug in the first place.
The evidence on digoxin in atrial fibrillation is worse than the evidence in heart failure. The AFFIRM analysis of 4,060 patients found that digoxin use was associated with a 41% higher risk of all-cause death and a 61% higher risk of arrhythmic death, regardless of whether the patient had heart failure [2]. A 2021 registry of 1,359 patients found that combining digoxin with a calcium channel blocker in patients without heart failure raised the risk of death nearly six-fold [1]. These are not small signals. They are consistent across large, independent datasets.
Digoxin does not prevent atrial fibrillation. The DIG trial analysis of 7,788 heart failure patients found that digoxin did not reduce the incidence of new atrial fibrillation at all: 10.7% on digoxin versus 11.5% on placebo [3]. A 1990 study of 72 patients with paroxysmal AF found that digoxin did not reduce the frequency of episodes but made the attacks last longer [6]. The VERDICT trial found that lone digoxin use was a predictor of rhythm control failure, with a hazard ratio of 2.2 [10]. So the drug is not keeping you in sinus rhythm.
What digoxin does is slow the ventricular rate during AF by blocking the AV node. But it does this poorly during exercise. A 1991 study found that digoxin lowered resting heart rate from 85 to 75 beats per minute, but at peak exercise the heart rate was the same as without the drug [9]. Beta-blockers and calcium channel blockers work better across the whole day. The CHARM analysis of 7,599 heart failure patients found that every 5-beat rise in heart rate over time predicted higher mortality, and a rise of more than 10 beats per minute predicted a 71% higher risk of death [4]. If stopping digoxin lets your heart rate rise, that is a real risk. But if you replace digoxin with a beta-blocker or a calcium channel blocker, your rate control will be better, not worse.
The proarrhythmic risk of digoxin is real. In ICD recipients, digoxin was associated with a 4-fold higher odds of receiving a shock [5]. In the PALLAS trial, adding dronedarone to digoxin raised arrhythmic death risk 22-fold [8]. The goat model showed that digoxin did not shorten atrial refractory periods or prolong AF duration, but it also did nothing to prevent the remodeling that makes AF permanent [7]. The drug is not protecting your heart from the arrhythmia.
| What the evidence shows | Digoxin | Without digoxin (on beta-blocker or CCB) |
|---|---|---|
| All-cause mortality risk | HR 1.41 (AFFIRM) [2] | Not directly studied, but beta-blockers reduce mortality in HF |
| Rate control at rest | Modest (75 bpm) [9] | Better with beta-blocker (63 bpm) [9] |
| Rate control during exercise | None [9] | Better with beta-blocker or verapamil [9] |
| AF episode prevention | None [3, 6] | Not studied head-to-head |
| Proarrhythmia risk | Higher shocks, higher arrhythmic death [5, 8] | Lower |
My call: stopping digoxin for atrial fibrillation is safe if you replace it with a beta-blocker or a calcium channel blocker. The drug was never a good long-term choice for rate control, and the mortality signal against it is strong. Do not stop it without a replacement, but do not stay on it either. Confidence: moderate. The evidence on digoxin's harm is consistent, but the direct withdrawal studies in AF are old and small.
Sources used 10
-
Impact of rate control medications on one-year outcomes with atrial fibrillation and heart failure
In a multicenter prospective registry of 1359 patients with persistent or permanent atrial fibrillation, the study found that rate-control regimens involving calcium channel blockers plus digoxin were associated with higher all-cause and cardiovascular mortality in patients with…
DOI: 10.1093/eurheartj/ehab724.0493 -
Increased mortality among patients taking digoxin--analysis from the AFFIRM study
This study analyzes data from the AFFIRM trial to determine the association between digoxin use and increased mortality rates among patients with atrial fibrillation, highlighting significant risks regardless of heart failure status.
DOI: 10.1093/eurheartj/ehs348 -
Incidence, Predictive Factors, and Prognostic Significance of Supraventricular Tachyarrhythmias in Congestive Heart Failure
In a large, multicenter DIG trial of congestive heart failure patients in sinus rhythm, the study quantified the incidence and baseline predictors of supraventricular tachyarrhythmias (SVT), demonstrated that SVT independently predicts higher all-cause mortality, stroke, and hos…
DOI: 10.1378/chest.118.4.914 -
Prognostic importance of temporal changes in resting heart rate in heart failure patients: an analysis of the CHARM program
Using data from 7599 heart failure patients in the CHARM program, this study shows that temporal increases in resting heart rate between clinic visits and higher time-updated heart rate predict higher mortality and cardiovascular events, while short-term decreases in heart rate …
DOI: 10.1093/eurheartj/ehu401 -
Digoxin Is Associated With Increased Shock Events and Electrical Storms in Patients With Implantable Cardioverter Defibrillators
Digoxin use among ICD recipients is associated with higher ICD shock events, more electrical storms, and increased hospitalizations, suggesting potential proarrhythmic risk in this population.
DOI: meta/10.1177/1074248417732416 -
Time of occurrence, duration, and ventricular rate of paroxysmal atrial fibrillation: the effect of digoxin.
This study investigates the occurrence, duration, and ventricular rate of paroxysmal atrial fibrillation in patients, revealing that digoxin treatment does not reduce the frequency of episodes but is associated with longer attacks.
DOI: 10.1136/hrt.63.4.225 -
Profibrillatory Effects of Verapamil but Not of Digoxin in the Goat Model of Atrial Fibrillation
This six-goat study directly compared the immediate and remodeling-phase effects of digoxin and verapamil on atrial fibrillation (AF): while digoxin slowed ventricular rate without altering AF cycle length or duration, verapamil shortened AF cycle length and refractory period in…
DOI: 10.1046/j.1540-8167.2000.01375.x -
Interaction Between Digoxin and Dronedarone in the PALLAS Trial
The study investigates the interaction between digoxin and dronedarone in patients with permanent atrial fibrillation, revealing that the combination significantly increases cardiovascular and arrhythmic mortality, particularly in those on digoxin therapy.
DOI: 10.1161/circep.114.002046 -
Effects of digoxin, propranolol, and verapamil on exercise in patients with chronic isolated atrial fibrillation
This study evaluates the effects of digoxin, propranolol, and verapamil on exercise performance and heart rate control in patients with chronic isolated atrial fibrillation, finding that while digoxin reduces heart rate at rest, propranolol and verapamil are more effective durin…
DOI: 10.1093/cvr/25.6.453 -
Verapamil Versus Digoxin and Acute Versus Routine Serial Cardioversion for the Improvement of Rhythm Control for Persistent Atrial Fibrillation
The VERDICT trial investigates the effectiveness of acute versus routine serial electrical cardioversion and the use of verapamil versus digoxin for rhythm control in patients with persistent atrial fibrillation, finding no significant advantage of acute strategies or verapamil …
DOI: 10.1016/j.jacc.2006.05.043