The Cardiac Arrhythmic Pilot Study - CAPS

Description:

Arrhythmia suppression for adverse events after myocardial infarction.

Hypothesis:

A method can be developed to identify and recruit patients post myocardial infarction with arrhythmia into an arrhythmia suppression trial.
Methods can be developed for antiarrhythmic drug and dose determination.
Treatment can suppress VPD rates by at least 70% in 80% of patients.
The efficacy and adverse effects of antiarrhythmic drugs over a one year period can be determined.

Study Design

Study Design:

Patients Screened: 4,000
Patients Enrolled: 502
Mean Follow Up: 12 months
Mean Patient Age: 59
Female: 17
Mean Ejection Fraction: 45% (<40% = 35% of population)

Patient Populations:

Recent acute myocardial infarction (6-60 days)
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 b-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

Asthma
Age < 75
> 10 VPD/hr or > five episodes of unsustained VT (3-9 consecutive VPD > 100 min) on 24 hour ambulatory arrhythmia monitor.

Exclusions:

LVEF < 20%
> 10 consecutive VPDs at a rate > 100/min (disqualifying VT)

Primary Endpoints:

Efficacy ( > 70% reduction in VPD and > 90% suppression of VPD runs) of different antiarrhythmic agents studied.

Secondary Endpoints:

Adverse effects
patient compliance with treatment routines

Drug/Procedures Used:

Encainide
Flecainide
Imipramine
Moricizine

Concomitant Medications:

Digoxin (23%)
Diuretics (32%)
Beta blockers (41%)
Calcium channel blockers (40%)
Potassium supplements (10%)

Principal Findings:

It is possible to identify and recruit patients for a definitive trial of post MI antiarrhythmias.

Agents capable of suppressing VPDs post infarct exist and seem well tolerated.

Patient compliance and follow-up in a post myocardial infraction setting can be maintained.

Efficacy rates higher with encainide (70%) and flecainide (83%) than with imipramine (52%) and moricizine (66%) or placebo (37%) (p = 0.01).

Encainide, flecainide, moricizine more effective than placebo (p = 0.001).

Adverse effects seen lower with encainide and flecainide than with imipramine, moricizine or placebo.

In the CAPS placebo group, 19% developed some serious clinical event in 1 year (death, heart failure, proarrhythmia) that could be attributable to antiarrhythmic drug toxicity. A significant reduction in the frequency of ventricular premature depolarizations (p = 0.004) occurred in the first few weeks of "therapy" with a further significant (p less than 0.04) decrease between 3 to 12 months.

Interpretation:

"More than 70% of the patients who started the follow-up phase on encaimide, flecainide or morizine remained on these drugs to the end of the study." Imipramine was excluded as a study drug to be used in the Cardiac Arrhythmia Suppression Trial (CAST).

References:

1. Am J Cardiol 1988;61:501-9 Trial design
2. American Journal of Cardiology 1989;63(7):393-8. CHF during follow-up
3. Circulation 1989;79(3):610-9. Final results
4. Journal of the American College of Cardiology 1991;17(1):1-8. Review

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias, Acute Heart Failure

Keywords: Digoxin, Hepatitis, Moricizine, Ventricular Fibrillation, Hypotension, Hypothyroidism, Encainide, Atrioventricular Block, Flecainide, Ventricular Premature Complexes, Patient Compliance, Myocardial Infarction, Imipramine, Hyperthyroidism, Heart Rate, Tachycardia, Ventricular, Peripheral Nervous System Diseases, Hypokalemia, Heart Failure, Bradycardia


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