Oral propafenone reduced symptomatic paroxysmal supraventricular arrhythmias
ACP J Club. 1991 Jul-Aug;115:13. doi:10.7326/ACPJC-1991-115-1-013
Pritchett EL, McCarthy EA, Wilkinson WE. Propafenone treatment of symptomatic paroxysmal supraventricular arrhythmias. A randomized, placebo-controlled, crossover trial in patients tolerating oral therapy. Ann Intern Med. 1991 Apr 1;114:539-44.
To evaluate the efficacy of oral propafenone in the prophylaxis of recurrent symptomatic arrhythmias in patients who could tolerate oral therapy and who had paroxysmal supraventricular tachycardia or paroxysmal atrial fibrillation.
Randomized, double-blind, placebo-controlled, crossover trial with each treatment phase lasting up to 60 days.
An outpatient clinic in the United States.
Patients not fully controlled by their current therapy, who could tolerate oral propafenone after a dose-finding phase, and who had symptomatic paroxysmal supraventricular tachycardia or paroxysmal atrial fibrillation documented by electrocardiogram, were included. Patients were excluded if paroxysms of arrhythmia precipitated angina, pulmonary edema, or neurologic symptoms. Patients with paroxysmal atrial fibrillation were excluded if they had the Wolff-Parkinson-White Syndrome. A stable dose of digoxin was allowed in the patients with fibrillation but other antiarrhythmic agents were prohibited in both groups.
23 patients (14 patients with paroxysmal supraventricular tachycardia and 9 patients with paroxysmal atrial fibrillation) were randomly assigned to either propafenone (dose determined by an initial dose-finding phase; 300 mg 3 times/d in 19 patients, 300 mg twice/d in 3 patients, and 150 mg twice/d in 1 patient) or placebo. Patients then crossed over to the alternate treatment after a 3-day washout period. Duration of follow-up was until arrhythmia recurrence or 60 days, whichever came first.
Main outcome measure
Recurrent symptomatic arrhythmia documented by telephone transmission of the electrocardiogram.
Compared with placebo, propafenone caused an increase in the time to the first recurrence of arrhythmia (P = 0.004). The estimated rate of symptomatic arrhythmia while receiving propafenone was 0.21 (hazard ratio, Poisson model, 95% CI 0.08 to 0.58) compared with placebo. Of 33 patients eligible for the study, 11 were unable to complete the randomized portion because of adverse effects.
Propafenone was effective in reducing symptomatic paroxysmal supraventricular arrhythmias in patients who could tolerate oral therapy and who had paroxysmal supraventricular tachycardia or paroxysmal atrial fibrillation.
Sources of funding: In part, Knoll Pharmaceutical Company; the National Heart, Lung, and Blood Institute; National Institutes of Health.
Address for article reprint: Dr. E.L. Pritchett, Box 3477, Duke University Medical Center, Durham, NC 27710, USA.
This study shows that propafenone, when tolerated by patients, reduces the rate of recurrence of both atrioventricular reciprocating tachycardia and atrial fibrillation to approximately one fifth of the recurrence rate without treatment. These data, in combination with a previous randomized, placebo-controlled trial in atrial fibrillation and several nonrandomized follow-up studies, provide a reasonable level of certainty that propafenone is an effective agent for these supraventricular arrhythmias, particularly atrial fibrillation. The double-blind, placebo-controlled methods used in this study provide the most unbiased estimate of drug efficacy and are clearly the best way to evaluate new drugs. The unique study end point of time to recurrence of symptomatic documented arrhythmia is an innovative approach that allows the researcher to use established analytic techniques of survival analysis.
Adverse experiences are not uncommon with propafenone and can include serious cardiac complications. Propafenone reduces sinus node automaticity (1). Significant sinus pauses may occur especially in patients with underlying sinus node disease. Wide complex, rapid tachycardias also may occur with propafenone. Most of these are caused by rapid conduction of a supraventricular tachycardia (2). For this reason pharmacologic blockade of atrioventricular nodal conduction (digitalis, β-blocker, or calcium antagonist) should be administered together with propafenone in patients with atrial fibrillation.
The data in this study provide further evidence that propafenone is useful for managing paroxysmal supraventricular tachycardias. The UK Propafenone PSVT study published in 1995 (3) provides further evidence that propafenone is effective in the prophylaxis of both paroxysmal supraventricular tachycardia and paroxysmal atrial fibrillation. At present, however, this agent is not approved in North America for this indication.
Stuart Connolly, MD
Hamilton General HospitalHamilton, Ontario, Canada
3. UK Propafenone PSVT Study Group. A randomized, placebo-controlled trial of propafenone in the prophylaxis of paroxysmal supraventricular tachycardia and paroxysmal atrial fibrillation. Circulation. 1995;92:2550-7.