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August 28, 2026Journal of the American College of CardiologyOpen Access

Ventricular rate control in chronic atrial fibrillation during daily activity and programmed exercise: a crossover open-label study of five drug regimens

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Key result

Digoxin plus atenolol reduces 24-hour ventricular rate by ~14 bpm vs digoxin alone in chronic AF.

  • P<0.0001
  • n=12

Why the study?

Systematic comparisons of standardized drug regimens on 24-hour ventricular rate control in chronic atrial fibrillation had not been reported.

Do different pharmacologic regimens (digoxin, diltiazem, atenolol, or their combinations) improve 24-hour ventricular rate control in patients with chronic atrial fibrillation?

Population

12 patients with chronic atrial fibrillation

Comparison

Digoxin vs diltiazem-CD vs atenolol vs digoxin plus diltiazem-CD vs digoxin plus atenolol

Design

Crossover open-label randomized trial

Follow-up

2 weeks per treatment

Authors

RFRamin FarshiDKDeborah KistnerJSJonnalagedda S.M. Sarma

Discussion

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Overview

In patients with chronic atrial fibrillation, combination therapy with digoxin and atenolol provides more effective 24-hour ventricular rate control than monotherapy with digoxin, diltiazem, or atenolol.

Key Points

  • To compare the effects of five standard pharmacologic regimens on circadian rhythm and exercise-induced ventricular rate changes in patients with chronic atrial fibrillation.
  • Conducted an open-label, randomized crossover trial in 12 patients (11 male, mean age 69 ± 6 years) with chronic atrial fibrillation.
  • Assigned 5 standardized oral regimens in random order for 2 weeks each: digoxin (0.25 mg), diltiazem-CD (240 mg), atenolol (50 mg), digoxin + diltiazem-CD, and digoxin + atenolol.
  • Evaluated 24-hour Holter monitoring and programmed exercise testing using repeated-measures ANOVA and cosinor analysis.
  • Mean 24-hour ventricular rate was 65.0 ± 9.4 bpm with digoxin + atenolol, 67.3 ± 14.1 bpm with digoxin + diltiazem, 75.9 ± 11.7 bpm with atenolol, 78.9 ± 16.3 bpm with digoxin, and 80.0 ± 15.5 bpm with diltiazem.
  • Digoxin + atenolol achieved significantly lower 24-hour ventricular rate compared to digoxin alone (p < 0.0001), diltiazem alone (p < 0.0002), and atenolol alone (p < 0.001).
  • During exercise, digoxin and digoxin + atenolol yielded the highest and lowest mean ventricular rates, respectively, while total exercise duration did not differ significantly among groups.

Study Design

Type

RCT (n=12)

Blinding

Open-label

Randomization

random order

Structured PICO

Do different pharmacologic regimens (digoxin, diltiazem, atenolol, or their combinations) improve 24-hour ventricular rate control in patients with chronic atrial fibrillation?

P
Population
12 patients (11 male, mean age 69 years) with chronic atrial fibrillation treated with 5 standardized daily regimens for 2 weeks each in a crossover design.
I
Intervention
5 standardized daily regimens assigned in random order for 2 weeks each: 1) 0.25 mg digoxin, 2) 240 mg diltiazem-CD, 3) 50 mg atenolol, 4) 0.25 mg digoxin + 240 mg diltiazem-CD, and 5) 0.25 mg digoxin + 50 mg atenolol.
C
Comparator
Each regimen compared against the others in a crossover design.
O
Outcome
24-h mean ventricular rate (VR) and exercise-induced changes.surrogate

Main Result

Absolute Event Rate: 65% vs 78.9%

p-value: p=< 0.0001

In patients with chronic atrial fibrillation, combination therapy with digoxin and atenolol provides more effective 24-hour ventricular rate control than monotherapy with digoxin, diltiazem, or atenolol.

Cite This Study

Farshi et al. (1999) conducted an RCT in chronic atrial fibrillation (CAF) (n=12). digoxin + atenolol vs. digoxin alone was evaluated on 24-h mean ventricular rate (VR) (p=< 0.0001). In patients with chronic atrial fibrillation, digoxin plus atenolol produced the most effective 24-hour ventricular rate control (mean 65.0 bpm) compared to digoxin alone (78.9 bpm, p<0.0001).

synapsesocial.com/papers/6a90fe1a73d671a805e3bb23https://doi.org/10.1016/s0735-1097(98)00561-0
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Also Consider

Synapse has enriched 3 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Relationships between heart rate, exercise tolerance and cardiac output in atrial fibrillation: the effects of treatment with digoxin, verapamil and diltiazem1988 · 69 citations
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  3. 3Early evening melatonin and S-20098 advance circadian phase and nocturnal regulation of core body temperature1997 · 196 citations