Beta-blocker heart attack trial: Impact of propranolol therapy on ventricular arrhythmias

doi:10.1016/0091-7435(85)90061-1

Preventive Medicine

Volume 14, Issue 3, May 1985, Pages 346-357

https://doi.org/10.1016/0091-7435(85)90061-1 Get rights and content

Abstract

The natural history of and the effect of propranolol on ventricular arrhythmias post-myocardial infarction were analyzed using data from the Beta-Blocker Heart Attack Trial (BHAT). The Beta-Blocker Heart Attack Trial was a multicenter, randomized, double-blind, placebo-controlled trial among 3,837 patients entered from 5 to 21 days after hospitalization for acute myocardial infarction. At baseline, prior to randomization, 3,290 (85.7%) patients underwent 24-hr ambulatory ECG monitoring which was repeated in approximately 25% of a randomly selected subset of the study population at 6 weeks. Ventricular arrhythmias were divided into eight different categories which defined the prevalence of ventricular arrhythmias in terms of frequency and/or complexity. Ventricular arrhythmias at baseline were associated with age, past history of myocardial infarction, and use of diuretics and digitalis. Paired data (baseline and 6-week) were available for 428 patients on propranolol and 412 on placebo. Propranolol markedly blunted the two- to threefold increase in ventricular arrhythmias that occurred from baseline to 6 weeks in the placebo group. Propranolol decreased the proportion of patients having ventricular arrhythmias during waking hours compared with sleep. These data show that propranolol has an antiarrhythmic effect and suggest that an antiarrhythmic mechanism may in part be responsible for the observed reduction in sudden cardiac death mortality in BHAT.

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Cited by (10)

Antiarrhythmic effect of carvedilol after acute myocardial infarction: Results of the Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction (CAPRICORN) trial
2005, Journal of the American College of Cardiology
Citation Excerpt :
The effect of beta-blockers on ventricular arrhythmias in the post-MI setting is more clearly established. Both substudies of the large beta-blocker secondary prevention trials and independent studies showed significant reductions in all grades of ventricular arrhythmias with propranolol, timolol, and metoprolol (9–13,26–29). None of these studies, however, focused on patients with substantial left ventricular systolic dysfunction; indeed, it seems that high-risk patients were excluded from these studies (22,23).
Whether beta-blockers reduce atrial arrhythmias and, when added to an angiotensin-converting enzyme (ACE) inhibitor, ventricular arrhythmia is unknown.
Ventricular and atrial arrhythmias are common after acute myocardial infarction (AMI) and are associated with a poor prognosis. Angiotensin-converting enzyme inhibitors reduce the incidence of both types of arrhythmia.
The antiarrhythmic effect of carvedilol was examined in a placebo-controlled multicenter trial, the Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction (CAPRICORN) study, which enrolled 1,959 patients with reduced left ventricular systolic function after AMI, 98% of whom were treated with an ACE inhibitor.
The incidence of atrial fibrillation/flutter was 53 to 984 (5.4%) in the placebo group and 22 to 975 (2.3%) in the carvedilol group, giving a carvedilol/placebo hazard ratio (HR) of 0.41 (95% confidence interval [CI] 0.25 to 0.68; p = 0.0003). The corresponding rates of ventricular tachycardia/flutter/fibrillation were 38 to 984 (3.9%) and 9 to 975 (0.9%) (HR 0.24, 95% CI 0.11 to 0.49; p < 0.0001).
Carvedilol has a powerful antiarrhythmic effect after AMI, even in patients already treated with an ACE inhibitor. Carvedilol suppresses atrial as well as ventricular arrhythmias in these patients.
Antiarrhythmic effects of beta-adrenergic blocking agents in benign or potentially lethal ventricular arrhythmias
1987, The American Journal of Cardiology
Classification of ventricualr arrhythmias into those that are benign, potentially lethal and lethal is based on their associated risk for producing sudden cardiac death. This classification system is useful in defining indications for the treatment of ventricular arrhythmias and predicting differential rates of antiarrhythmic drug efficacy and toxicity. Whether the reduction of potentially lethal ventricular arrhythmias will prevent sudden cardiac death remains to be determined. The class II antiarrhythmic agents—the β-adrenergic blocking drugs—have been shown to reduce sudden cardiac death in postmyocardial infarction patients, but the precise mechanism of their effect has not been defined, β blockers are efficaclous in approximately 50% of patients with benign or potentially lethal ventricular arrhythmias. This response is comparable to that seen with the class IA agent disopyramide or the class IB agents tocainide and mexiletine. β blockers have favorable side-effect profiles including a low incidence of proarrhythmia and a lack of organ toxicity such as hepatitis, pulmonary fibrosis or agranulocytosis, which are concerns with class I and class III antiarrhythmic drugs. The proper dosage of the β blocker is critical in limiting adverse effects. In a study of 23 patients with benign or potentially lethal ventricular arrhythmias, 11 (48%) of the patients responded to nadolol with a reduction of >75% in arrhythmia frequency, and several patients responded at nadolol dosages as low as 10 mg daily. Thus, it is plausible to consider β blockers as first-choice antiarrhythmic therapy, even in patients with left ventricular dysfunction when sympathetic tone is not required to maintain cardiac compensation.
Effectiveness of low-dose nadolol for ventricular arrhythmias
1986, The American Journal of Cardiology
To determine the minimal effective dose of nadolol to suppress frequent ventricular premature complexes (VPCs), 23 patients with at least 30 VPCs/hour on 2 baseline 24-hour Holter recordings were studied. The initial dose of nadolol was 10 mg/day orally, and this dose was doubled at weekly intervals until arrhythmia suppression was achieved, adverse effects appeared, or a maximal dose of 160 mg/ day was reached. After each dose level a 24-hour ambulatory Holter monitor was recorded. A pharmacokinetic trial was conducted in patients who responded to nadolol treatment. Frequent VPCs were suppressed at least 75% by nadolol in 11 of 23 patients (48%) and the minimal effective dose was 10 mg/day in 3 patients, 20 mg/day in 4, 40 mg/ day in 3 and 80 mg/day in 1 patient. At these doses, minimal steady-state levels of nadolol in serum (Cmin) ranged from 3.9 to 47.0 ng/ml, and these serum concentrations were proportional to the oral dose of nadolol (r = 0.753, p < 0.001). No relation, however, was observed between Cmin levels and percent reduction of VPCs. Cmin and heart rate changes were comparable between responders and nonresponders, suggesting that the degree of β blockade was similar between these 2 groups. Adverse reactions were noted in 6 patients, and 2 had an asymptomatic increase in the frequency of VPCs and 1 patient an increase in beats of ventricular tachycardia. This study details the importance of selecting an individualized dose for nadolol for control of ventricular arrhythmias; in more than half of the patients doses of 20 mg/day or less were effective.
Propranolol versus Other Selected Drugs in the Treatment of Various Types of Anxiety or Stress, with Particular Reference to Stage Fright and Post-Traumatic Stress Disorder
2022, International Journal of Molecular Sciences
Effect of four classes of antihypertensive drugs on cardiac repolarization heterogeneity: A double-blind rotational study
2020, PLoS ONE
Propranolol: A 50-year historical perspective
2019, Annals of Indian Academy of Neurology

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Beta-blocker heart attack trial: Impact of propranolol therapy on ventricular arrhythmias

Abstract

Beta-Blocker Heart Attack Trial Protocol

National Institutes of Health Publication 81-2209

Beta-Blocker Heart Attack Trial: Design features

Controlled Clin. Trials

A randomized trial of propranolol in patients with acute myocardial infarction. I. Mortality results

JAMA

A randomized trial of propranolol in patients with acute myocardial infarction. II. Morbidity results

JAMA

Ventricular arrhythmias in ischemic heart disease: Mechanism, prevalence, significance and management

Prog. Cardiovasc. Dis.

Prevalence, characteristics and significance of ventricular tachycardia (3 or more complexes) detected with ambulatory electrocardiographic monitoring in the late hospital phase of acute myocardial infarction

Amer. J. Cardiol.

The effect of propranolol on mortality in patients following acute myocardial infarction with complex ventricular arrhythmias

Circulation

Ventricular premature beats in a population sample

Circulation

The relationship of paroxysmal ventricular tachycardia complicating the acute phase of myocardial infarction to long-term survival

Amer. J. Med.

One year's treatment with propranolol after myocardial infarction: Preliminary report of Norwegian multicentre trial

Brit. Med. J.

Ventricular premature beats and coronary death risk factors

Amer. J. Epidemiol.

Arrhythmias in acute myocardial infarction

Dis. Chest

A controlled trial of sotalol for one year after myocardial infarction

Lancet

Disturbances of rate, rhythm and conduction in acute myocardial infarction

Amer. J. Med.

A validation technique for computerized Holter tape processing systems used in drug efficiency testing

The effect of age, blood pressure and gender on the incidence of premature ventricular contractions

Angiology

Effect of propranolol on ventricular arrhythmia—the Beta-Blocker Heart Attack Trial Experience

Circulation