AF rate control: beta-blocker vs digoxin choices — viva

Stem

Practice viva. A 68-year-old man with AF is referred from the emergency department with a ventricular rate of 128 beats per minute. He is haemodynamically stable with no pre-excitation. The examiner works through drug choice by ejection fraction, acute versus long-term control, digoxin, heart rate targets and atrioventricular node ablation. Answer for a non-pregnant adult.

Branch A — What do you need to know before choosing a drug?

Examiner: What decides which rate-control drug you give him?

Strong answer:

• ESC 2024 says the choice of drug will depend on the patient's characteristics, presence of heart failure and LVEF, and haemodynamic profile.^[1]
• ESC 2024 also says physicians should always evaluate and manage underlying causes before, or in parallel to, acute rate control, such as treating sepsis, addressing fluid overload or managing cardiogenic shock.^[1]
• ESC 2024 recommends a transthoracic echocardiogram in patients with an AF diagnosis where this will guide treatment decisions (Class I, Level C).^[1]

Follow-up: His LVEF is 60%. Which drugs are first choice under ESC 2024?^[1]

• ESC 2024: beta-blockers, diltiazem, verapamil or digoxin are recommended as first-choice drugs in AF with LVEF above 40%, to control heart rate and reduce symptoms (Class I, Level B).^[1]
• ESC 2024 says that, in general, for acute rate control, beta-blockers (for all LVEF) and diltiazem or verapamil (for LVEF above 40%) are preferred over digoxin because of their more rapid onset of action and dose-dependent effects.^[1]
• ACC/AHA 2023 recommends beta blockers or nondihydropyridine calcium channel blockers (verapamil, diltiazem; provided that EF is above 40%) for acute rate control in haemodynamically stable AF with rapid ventricular response (COR 1, LOE B-R).^[3]

Branch B — The ejection fraction is 30%

Examiner: Suppose instead his LVEF were 30%. What changes?^[4]

Strong answer:

• ESC 2024 AF: beta-blockers and/or digoxin are recommended with LVEF of 40% or less, to control heart rate and reduce symptoms (Class I, Level B).^[1]
• ESC 2026 HF ranks them: beta-blockers first-line in stable HFrEF and AF for short- and long-term rate control (Class I, Level C), and digoxin when the rate remains high despite beta-blockers, or beta-blockers are contraindicated or not tolerated (Class IIa, Level C).^[4]
• Verapamil and diltiazem are out: ESC 2024 Table 12 lists them as contraindicated if LVEF is 40% or less, and ACC/AHA 2023 classes intravenous nondihydropyridine calcium channel blockers in known moderate or severe LV systolic dysfunction as harm (COR 3: Harm, LOE B-NR).^[1][3]

Follow-up: Do beta-blockers improve survival in heart failure with AF?^[21]

• In an individual-patient meta-analysis of ten placebo-controlled heart failure trials (rhythm classified at baseline; mean follow-up 1.5 years), beta-blockers significantly reduced all-cause mortality in sinus rhythm (HR 0.73) but not in AF (HR 0.97).^[21]
• ESC 2024 AF says the prognostic benefit of beta-blockers seen in HFrEF with sinus rhythm may not be present in AF; of the older HFrEF therapies, including beta-blockers, it adds that these drugs have clear proof of safety and there may be other indications for them beyond prognosis, including comorbidity management and symptom improvement.^[1]

Branch C — Digoxin and digitoxin

Examiner: Tell me about digoxin. Is it safe?^[1]

Strong answer:

• ESC 2024: digoxin and digitoxin inhibit the sodium–potassium adenosine triphosphatase and augment parasympathetic tone.^[1]
• ESC 2024: in RCTs there is no association between digoxin and any increase in all-cause mortality, and lower doses may be associated with better prognosis.^[1]
• A systematic review and meta-analysis of observational and controlled trial data on digoxin against control (placebo or no treatment), covering studies published from 1960 to July 2014, found a pooled risk ratio for death of 1.76 in unadjusted analyses but 0.99 in randomised controlled trials, and concluded that prescription biases limit the value of observational data; ACC/AHA 2023 notes that the randomised trials in that subanalysis were in patients with concomitant HF.^[12][3]
• ACC/AHA 2023: where measuring serum digoxin levels is indicated, it is reasonable to target levels below 1.2 ng/mL (COR 2a, LOE B-NR).^[3]

Follow-up: How does digitoxin differ from digoxin?^[4]

• ESC 2026 HF: both glycosides share a narrow therapeutic window and need careful monitoring, but digoxin is primarily eliminated through the kidneys whereas digitoxin undergoes hepatic elimination.^[4]
• ESC 2024 Table 12 lists digitoxin 0.4–0.6 mg intravenously and a usual oral maintenance range of 0.05–0.1 mg once daily for rate control.^[1]

Branch D — How low should the rate go?

Examiner: You have started bisoprolol. What resting heart rate are you aiming for?^[1]

Strong answer:

• ESC 2024: lenient rate control with a resting heart rate below 110 b.p.m. should be considered as the initial target, with stricter control reserved for those with continuing AF-related symptoms (Class IIa, Level B).^[1]
• RACE II randomised 614 patients with permanent AF to lenient (resting below 110 beats per minute) or strict control (resting below 80, and below 110 during moderate exercise); the estimated cumulative incidence of the primary composite at 3 years was 12.9% against 14.9%, and lenient control was non-inferior.^[9]
• ACC/AHA 2023 notes the limits: the groups differed by only 10 bpm, and patients with HF were underrepresented.^[3]

Branch E — Drugs have failed

Examiner: A year later his rate is uncontrolled despite combination therapy and he is not a candidate for rhythm control. What now?^[1]

Strong answer:

• ESC 2024: atrioventricular node ablation in combination with pacemaker implantation should be considered in patients unresponsive to, or ineligible for, intensive rate and rhythm control therapy, to control heart rate and reduce symptoms (Class IIa, Level B).^[1]
• ACC/AHA 2023: the pacemaker is implanted before the ablation (before or on the same day) to ensure adequacy of the pacing leads (COR 1, LOE B-NR), and with a persistently rapid ventricular response the initial lower rate is 80 to 90 bpm to reduce the risk of sudden death (COR 1, LOE C-LD).^[3]
• ESC 2024 text: due to its broad extracardiac adverse effect profile, amiodarone is reserved as a last option when heart rate cannot be controlled even with maximal tolerated combination therapy, or for patients who do not qualify for atrioventricular node ablation and pacing.^[1]

Follow-up: And if he had been admitted with heart failure?^[1][4]

• ESC 2024: atrioventricular node ablation combined with CRT should be considered in severely symptomatic permanent AF and at least one HF hospitalisation, to reduce symptoms, physical limitations, recurrent HF hospitalisation and mortality (Class IIa, Level B).^[1]
• ESC 2026 HF restates the row for severely symptomatic permanent AF with poor rate control despite medical therapy and at least one HF hospitalisation, to reduce symptoms, physical limitations, recurrent HF hospitalisation and death (Class IIa, Level B1).^[4]
• APAF-CRT (133 patients with severely symptomatic permanent AF for more than 6 months, narrow QRS of 110 ms or less and at least one HF hospitalisation in the previous year) was stopped for efficacy at interim analysis after a median of 29 months of follow-up: all-cause death 11% with Ablation + CRT against 29% with drugs (HR 0.26).^[11]