Amiodarone in Patients with Congestive Heart failue and Asymptomatic Ventricular Arrhythmia - CHF STAT

Description:

Amiodarone for mortality in congestive heart failure.

Hypothesis:

Amiodarone can prolong survival among patients with heart failure and asymptomatic but frequent and complex ventricular arrhythmias.

Study Design

Study Design:

Patients Screened: 1,303
Patients Enrolled: 674
Mean Follow Up: 45 months (54 months)
Mean Patient Age: 65
Female: 1
Mean Ejection Fraction: 66% with ejection fraction, < 30%; 34% with ejection, fraction 30-40%

Patient Populations:

History of congestive heart failure; ischemic or nonischemic
Asymptomatic ventricular arrhythmia (at least > 10 VPD's/hr)
Ejection fraction < 40%
Receiving vasodilator (preferably ACE inhibitor) therapy; +/- digitalis; diuretics

Exclusions:

Women of child bearing age
Recent myocardial infarction
Symptomatic ventricular arrhythmia
History of aborted cardiac arrest or sustained ventricular tachycardia
Other antiarrhythmic treatment
Systolic BP < 90 mmHg
ECG with QRS > 180 msec or Qtc > 500 msec

Primary Endpoints:

Total mortality
Sudden cardiac death syndrome

Secondary Endpoints:

Ejection fraction
Suppression of ventricular arrhythmias

Drug/Procedures Used:

24 hour ambulatory arrhythmia
Chest x-ray
Pulmonary function tests
Arterial blood gases
Echocardiography
Radionuclide ejection fraction
Amiodarone (800 mg QD x 14 days; then 400 mg QD for 50 weeks; then 300 mg QD).

Concomitant Medications:

Beta blocker (4%)
Digitalis (70%)
ACE inhibitor (78%)
Hydralazine/ISDN (4%)
Furosemide (83%)

Principal Findings:

No significant difference in overall mortality between the two treatment groups (p = 0.6).

At 2 years, sudden death rate was 15% in Amiodarone group and 19% in placebo group (p =0.43).

Amiodarone was effective in suppressing ventricular arrhythmias and increased LVEF by 42% at 2 years. (LVEF 35% in Amiodarone group versus 29% in placebo; p < 0.001).

Trend toward reduction in overall mortality among patients with nonischemic cardiomyopathy in Amiodarone group (p = 0.07).

Study medication stopped due to side-effects in 27% of Amiodarone group and 23% of placebo patients.

In terms of pulmonary function, there were no significant differences between the groups at baseline or at years 1 and 2. Pulmonary fibrosis was diagnosed in four patients (1.1%) treated with amiodarone and in three patients (0.8%) receiving placebo.

Compared with the placebo group, ejection fraction increased more in the amiodarone group at each time point (8.1 +/- 10.2% [mean +/- SD] versus 2.6 +/- 7.9% at 6 months, 8.0 +/- 10.9% versus 2.7 +/- 8.0% at 12 months, and 8.8 +/- 10.1% versus 1.9 +/- 9.4% after 24 months, all P < .001). However, this difference was not associated with greater clinical improvement, lesser diuretic requirements, or fewer hospitalizations for heart failure.

Amiodarone does not influence the circadian pattern of sudden cardiac death.

Nonsustained ventricular tachycardia was present in 80% of all patients. However, after adjusting other variables, especially for EF, NSVT was not an independent predictor of all-cause mortality or sudden death.

Interpretation:

Although amiodarone therapy increased left ventricular ejection fraction in patients with congestive heart failure, this was not associated with clinical benefit in the population as a whole. The substantial reduction in the combined end point of cardiac death plus hospitalizations for heart failure in the nonischemic group suggests possible benefit in these patients. Pulmonary toxicity appears acceptable in this patient group. The failure of NSVT to predict fatal outcomes implies that suppression of these arrhythmias may not improve survival.

References:

1. Am J Cardiol 1993;72:99F-102F. Study design
2. N Engl J Med 1995;333:77-82. Final results (2-year survival)
3. Circulation 1996;93:2128-34. EF and survival
4. Am J Cardiol 1997;80:45-8. Circadian pattern of sudden death
5. J Am Coll Cardiol 1997;30:514-7. Pulmonary effects
6. J Am Coll Cardiol 1998;32:942-7. NSVT prevalence

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Noninvasive Imaging, SCD/Ventricular Arrhythmias, Acute Heart Failure, Echocardiography/Ultrasound

Keywords: Radioisotopes, X-Rays, Ventricular Fibrillation, Diuretics, Respiratory Function Tests, Vasodilator Agents, Fatal Outcome, Tachycardia, Ventricular, Cardiomyopathies, Heart Failure, Digitalis, Stroke Volume, Pulmonary Fibrosis, Hospitalization, Death, Sudden, Cardiac, Echocardiography


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