Canadian Amiodarone Myocardial Infarction Arrhythmia Trial (Pilot) - CAMIAT

Description:

Amiodarone for mortality in patients at high risk or sudden death.

Hypothesis:

Antiarrhythmic drug therapy with amiodarone might reduce mortality in patients identified to be at high risk of sudden death from VPDs.

Study Design

Study Design:

Patients Screened: 4,800
Patients Enrolled: 1,202
Mean Follow Up: 1.79 years
Mean Patient Age: 64
Female: Amiodarone = 21%; placebo = 22%

Patient Populations:

Acute myocardial infarction (MI) within the previous 6-45 days based on the presence of two of three of the following criteria:
Characteristic ischemic pain in the precordium or associated referral areas for at least 20 minutes during physical and emotional rest.
Activities of creatine kinase or aspartate aminotransferase >2 times the upper limit or the presence of creatine kinase MB of 6% or more than that of the total activity of creatinine kinase [MB is a measurement of creatine phosphokinase isoenzyme MB bands of cardiac muscle].
Development of new 40 ms Q-waves in at least two adjacent ECG leads or the development of a dominant R-wave in V1 (R >1 mm and S >1 mm in V1).
10 or more VPDs /h or more (>18 h of monitoring required) or at least one run of ventricular tachycardia (VT) on 24-h electrographic recording (>3 beats at a rate of 100-200/min, or 3-10 beats at a rate >120/min).
Age > 19 years.

Exclusions:

Contraindications to amiodarone (previous intolerance or current therapy, waking bradycardia, sustained heart rate >50/min, PR interval of 220 ms or more, first-, second- or third-degree atrioventricular block, prolonged QTC interval (>480 ms), moderate or severe peripheral neuropathy, chronic or acute hepatitis, suggestion of interstitial fibrosis on chest radiographs, clinical hyperthyroidism or hypothyroidism or current therapy for these conditions).
Requirement of antiarrhythmic therapy (run of VT for 6 beats or more and rate of 100 bpm or more, atrial or ventricular arrhythmia that in the opinion of the treating physician required antiarrhythmic drugs other than β-blockers or digoxin), tricyclic antidepressant drugs, sotalol or phenytoin.
Medical factors (NYHA class IV congestive heart failure, CCVS class IV angina, severe hypotension, uncorrected hypokalemia, noncardiac illness likely to shorten survival significantly to less than two years, and women of childbearing potential).
Geographic or social factors making study participation impractical.
Astha.

Primary Endpoints:

Composite of resuscitated ventricular fibrillation or arrhythmic death

Secondary Endpoints:

Arrhythmic death
Cardiac death
All-cause mortality

Drug/Procedures Used:

Amiodarone: loading dose 10 mg/kg/day to the nearest 100 mg for 3 weeks, adjusted as required for drug intolerance or potentially serious side effects
Maintenance dose: 300- 400 mg/day depending on body weight, adjusted to reflect Holter monitor results.
If arrhythmia suppression was detected, the dose of amiodarone or placebo was reduced to 200-300 mg daily at month 4 and to 200 mg for 5 or 7 days per week at month 8. If arrhythmia suppression was not detected on repeat ambulatory ECG, the dose was not reduced. The duration of treatment was 24 months.

Concomitant Medications:

β-blocker
Calcium channel antagonists
Digoxin
Thrombolytic agents
Warfarin
Aspirin
ACE inhibitor

Principal Findings:

For amiodarone patients, VPD suppression at week 1 was 63%; at week 2, 85%.

For placebo patients, VPD suppression at week 1 was 17%, at week 2, 27%.

Arrhythmic death or resuscitated VF occurred in 15 (3.3%) of amiodarone patients, and 31 (6%) of placebo patients (relative-risk reduction: 48.5% [95% confidence interval 4.5 to 72.2], p = 0.016).

In the intention-to-treat analysis, primary outcome events occurred in 24 (6.9%) patients in the placebo group and in 15 (4.5%) in the amiodarone group (relative-risk reduction: 38.2% [95% confidence interval -2.1 to 62.6], p = 0.029).

The absolute-risk reductions were greatest among patients with congestive heart failure or a history of myocardial infarction.

All-cause mortality was 10% in amiodarone patients, 21% in placebo patients.

Except for thyroid stimulating hormone elevation and skin reactions, no side effects occurred more frequently with amiodarone.

The study drug was stopped for side effects or noncompliance in 35% of amiodarone patients and 34% of placebo patients.

Interpretation:

Amiodarone reduces the incidence of ventricular fibrillation or arrhythmic death among survivors of acute myocardial infarction with frequent or repetitive VPDs. Amiodarone, in moderate loading and maintenance dosages with adjustments in response to plasma levels, VPD suppressions, and side effects, results in effective VPD suppression and acceptable levels of toxicity.

References:

1. Circulation 1991;84:550-57. Pilot study
2. Am J Cardiol 1993;72:87F-94F. Rationale and protocol
3. Lancet 1997;349:675-682. Final results

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, EP Basic Science, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure

Keywords: Myocardial Infarction, Creatine Kinase, Risk Reduction Behavior, Ventricular Fibrillation, Pain, Thyrotropin, Tachycardia, Ventricular, Heart Failure, Electrocardiography, Ambulatory, Ventricular Premature Complexes, Death, Sudden, Cardiac


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