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Amiodarone, Losartan, and Perindopril in Atrial Fibrillation - Amiodarone, Losartan, and Perindopril in Atrial Fibrillation
Description:
The goal of the trial was to compare amiodarone alone with amiodarone plus either losartan or perindopril for the prevention of recurrent atrial fibrillation (AF) in patients with lone paroxysmal AF.
Study Design
Study Design:
Patients Screened: 280
Patients Enrolled: 177
Mean Follow Up: 2 years
Mean Patient Age: Mean age 58 years
Female: 35
Mean Ejection Fraction: Baseline mean ejection fraction 66%
Patient Populations:
Symptomatic paroxysmal AF with ≥5 AF episodes per year, at least two of which were documented on Holter or 12-lead ECG, and New York Heart Association class I or II
Exclusions:
Structural heart disease; hypertension; left atrium size >40 mm; ejection fraction <50%; hyperthyroidism or electrolyte disturbance, pulmonary or hepatic diseases, or other contraindications to treatment with amiodarone; significant impairment of renal function; QT interval ≥480 ms in the absence of bundle-branch block; bradycardia ≤55 bpm while the patient was awake; significant alternations of the atrioventricular conduction; sick sinus syndrome
Primary Endpoints:
Incidence of AF (lasting >30 seconds) on 12-lead ECG or Holter after 14 days and within 24 months after randomization
Drug/Procedures Used:
Patients were randomized to amiodarone alone (n = 59), amiodarone plus losartan (n = 59), or amiodarone plus perindopril (n = 59). Amiodarone dosing was 600 mg/d for the first week, 400 mg/d for the second week, and 200 mg/d for the remainder of the study. Losartan dosing was 50 mg/d for 2 weeks, followed by 100 mg/d if no hypotension occurred. Perindopril dosing was 2 mg/d for 3 days, followed by 4 mg/d if no hypotension occurred. Patients underwent echocardiography and Holter at 6, 12, 18, and 24 months.
Principal Findings:
Baseline characteristics were similar across the treatment groups, with an average of 1.8 AF episodes per month. Duration of AF was somewhat longer in the amiodarone plus perindopril group (2.0 years vs. 2.6 years for amiodarone alone and 2.7 years for amiodarone plus losartan).
Compared with the amiodarone alone group, the primary endpoint of AF by 24 months occurred less frequently in the amiodarone plus losartan group (19% vs. 41%, p = 0.006) and the amiodarone plus perindopril group (24% vs. 41%, p = 0.04), with no significant difference between the amiodarone plus losartan and amiodarone plus perindopril group (p = NS).
Left atrial diameter at 24 months was significantly smaller in the amiodarone plus losartan group and the amiodarone plus perindopril group compared with the amiodarone alone group (36 mm and 35 mm vs. 38 mm, respectively; p < 0.001 for each). There was no significant difference in the frequency of serious adverse events (8.5% for amiodarone alone and amiodarone plus losartan groups, 14% for amiodarone plus perindopril group).
Interpretation:
Among patients with lone paroxysmal AF, treatment with amiodarone plus losartan or amiodarone plus perindopril was associated with a reduction in recurrent AF through 2 years of follow-up compared with amiodarone alone.
Prior studies have suggested that the addition of an angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin-receptor blocker (ARB) to amiodarone therapy may prevent recurrent AF. However, earlier studies included patients with left ventricular (LV) dysfunction and hypertension, and therefore, it was unclear if the improvements were due to antiarrhythmic effects of the ACE-I/ARB or to LV function or blood pressure effects of the ACE-I/ARB. The present study included only lone AF patients to avoid this uncertainty.
References:
Yin Y, Dalal D, Liu Z, et al. Prospective randomized study comparing amiodarone vs. amiodarone plus losartan vs. amiodarone plus perindopril for the prevention of atrial fibrillation recurrence in patients with lone paroxysmal atrial fibrillation. Eur Heart J 2006;27:1841-6.
Keywords: Perindopril, Losartan, Heart Atria, Receptors, Angiotensin, Hypotension, Blood Pressure, Electrocardiography, Atrial Fibrillation, Hypertension, Echocardiography
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