Comparison of Propafenone Versus Procainamide forthe Acute Treatment of Atrial Fibrillation After

Cardiac SurgeryPeter Geelen, MD, PhD, Gilles E. O’Hara, MD, Nathalie Roy, MD, Mario Talajic, MD,

Denis Roy, MD, Sylvain Plante, MD, and Jacques Turgeon, PhD

The occurrence of atrial fibrillation (AF) early aftercardiac surgery is common. AF may develop in up

to 40% of patients after coronary artery bypass graft-ing (CABG) and in .50% of patients undergoingvalvular surgery.1–3 The goals of treating postopera-tive AF are primarily to restore sinus rhythm and/or tocontrol the ventricular response. Electrical cardiover-sion can be used but is less effective in the earlypostoperative period, making medical treatment thefirst therapeutic option.4 Beta-blocking drugs, vera-pamil, and digoxin can be used to control the ventric-ular rate during AF, but these drugs do not restoresinus rhythm. Intravenous procainamide is often usedto chemically convert atrial fibrillation, and althoughthe drug is moderately effective for that purpose,5,6 itsometimes increases the ventricular response andcauses arterial hypotension due to the vagolytic andvasodilator effects of the drug. Class Ic drugs havebeen shown to be highly efficient for pharmacologiccardioversion of atrial fibrillation, probably because oftheir rate-dependent effects on the electrophysiologicproperties of atrial tissue.7,8 We therefore studied theefficacy of intravenous propafenone, a class Ic antiar-rhythmic drug that also possessesb-blocking properties,in the treatment of postoperative AF and compared itwith treatment with intravenous procainamide.

• • •Sixty-two consecutive patients, 42 men and 20

women, 48 to 79 years old (mean 676 7), who hadundergone CABG or valvular surgery within 3 weeksand developed sustained (.30 minutes) AF were se-lected for the study. All patients gave written in-formed consent before the surgery. Exclusion criteriawere age.80 years, documented conduction distur-bances exceeding first-degree atrioventricular block,AF before surgery, concomitant therapy with class I orclass III antiarrhythmic drugs, severe obstructive pul-monary disease, acute myocardial infarction, AF last-ing .48 hours, AF with a slow (,80/minute) ventric-ular response, and systolic blood pressure,90 mmHg or hypotension requiring inotropic support. Acomplete medical history, physical examination, rou-

tine laboratory testing, and a 12-lead electrocardio-gram were obtained before administration of the drug.

A double-blind randomized study design was used,where each patient received either intravenouspropafenone at a dose of 2 mg/kg in 10 minutes (n529) or intravenous procainamide 20 mg/kg, to a max-imum of 1,000 mg, at a rate of 30 mg/min (n5 33).To assure double blinding, after termination of the10-minute infusion, a second infusion was started withan equivalent volume of either 5% glucose solution (inpatients receiving propafenone) or 20 mg/kg procain-amide to complete the procainamide dose. Other drugsto control the ventricular response were not allowedafter starting infusion of the study drug. Blood pres-sure was noninvasively measured every 5 minutesduring the infusion, and every 15 minutes during 1hour thereafter. Hypotension was defined as a de-crease in systolic blood pressure to,100 mm Hg andwas called symptomatic if accompanied by dizzinessor diminished well-being. Continuous telemetry andHolter monitoring was performed during the infusionand for $12 hours after the end of the infusion. A12-lead electrocardiogram was obtained as soon asconversion to sinus rhythm occurred. Conversion tosinus rhythm was attributed to the drug if it occurredduring drug delivery or within 15 minutes of the endof the infusion. Slowing or acceleration of the ven-tricular response during AF (average ventricular re-sponse on Holter during 1 minute measured afterstarting the infusion) was attributed to the drug whena decrease or increase$10% compared with baselinewas noted.

Mean values6 SD were given for continuousvariables and were analyzed by means of Student’sttest for unpaired variables or the nonparametric Mann-Whitney test in case of non-Gaussian distribution.Differences in proportions were calculated using Fish-er’s exact test.

The 2 study groups were fully comparable withrespect to baseline clinical variables (Table I). Fifteenminutes after starting drug infusion, 17 of 29 patients(59%) receiving propafenone had converted to sinusrhythm compared with 6 of 33 patients (18%) onprocainamide (p,0.001, Figure 1). Average time torestore sinus rhythm was 166 14 minutes forpropafenone versus 286 15 minutes for procainamide(p ,0.02). One hour after starting drug infusion, 76%of patients receiving propafenone compared with 61%of patients on procainamide were in sinus rhythm (p5NS). During the first 30 minutes after starting theinfusion, the ventricular rate increased$10% in 11patients (33%) receiving procainamide compared with

From the Quebec Heart Institute, Laval Hospital, Sainte-Foy, Quebec;University Hospital Sherbrooke, Sherbrooke, Quebec; and Depart-ment of Medicine, Montreal Heart Institute, Montreal, Quebec, Can-ada. This study was supported by a grant from the Fonds de laRecherche en Sante du Quebec, Montreal, Quebec; Knoll Pharma-ceuticals Canada Inc, Markham, Ontario; and by Bristol-Meyers-Squibb Canada Inc, Montreal, Quebec, Canada. Dr. O’Hara’s ad-dress is: Quebec Heart Institute, Laval Hospital, Sainte-Foy, Quebec,G1V 4G5, Canada. E-mail: Gilles.Ohara@med.ulaval.ca. Manu-script received January 12, 1999; revised manuscript received andaccepted March 23, 1999.

345©1999 by Excerpta Medica, Inc. All rights reserved. 0002-9149/99/$–see front matterThe American Journal of Cardiology Vol. 84 August 1, 1999 PII S0002-9149(99)00292-1

2 patients (8%) who were on propafenone (p,0.025).In contrast, the ventricular rate decreased$10% in 16patients (55%) on propafenone versus 9 patients(27%) in the procainamide group (p,0.05). Concom-itant drug use had no effect on conversion rates in bothtreatment groups.

Almost 1/3 of patients in both groups experiencedtransient mild adverse effects (Table II). In 3 patients(9%) receiving procainamide, however, drug infusionhad to be discontinued due to severe symptomatichypotension. We noted a higher incidence of hypoten-sion in patients treated with procainamide (27% vs 7%in patients on propafenone, p,0.05). No proarrhyth-mia was seen in any of the patients.

• • •In this study we have shown that a 10-minute

infusion of the class Ic drug propafenone causes rapidcardioversion in almost 60% of patients and has afavorable effect on the ventricular response duringAF. The frequently used class Ia drug procainamidetakes longer to administrate, is less effective for acutecardioversion, may increase the ventricular rate duringAF, and causes hypotension in a significant proportionof patients. The principles of treating postoperativeAF are similar to treatment principles for AF in gen-eral: control of ventricular rate, prevention of throm-boembolism, and conversion to sinus rhythm. Controlof ventricular rate can often be achieved by usingbblockers, calcium antagonists, and digoxin, althoughthe latter drug is often ineffective in the postoperativeperiod with the presence of excess catecholamines.4 Inmany patients, however, not only rate control but therestoration of sinus rhythm is of paramount impor-tance to improve hemodynamics and to prevent post-operative thromboembolism. The atrial contractioncontributes importantly to ventricular filling, espe-cially in patients with a diminished left ventricularfunction or in patients suffering from diastolic dys-

function caused by hypertrophic or hypertensive heartdisease. Electrical cardioversion can be used, but thisrequires additional anesthesia and success rates in thepostoperative setting are less due to pericardial in-flammation and a decreased intrathoracic conduc-tance.4

One would prefer a drug that can simply and rap-idly be administered, is effective with a rapid onset ofaction, and does not cause significant side effects.Although conversion rates on propafenone and pro-cainamide were similar after 1 hour in our study, thefact that propafenone achieved cardioversion earlier(realizing that, at that time, the full dose of procain-amide was not yet infused) is an important advantagewhen treating postoperative AF in an intensive caresetting.

Several studies have reported on the effectivenessof propafenone in terminating AF.9–12 Conversionrates in several placebo-controlled trials vary between55% and 91% depending on patient population studiedand duration of AF. Many studies also indicate asignificant decrease in the ventricular response inpatients not converted to sinus rhythm, generally as-cribed to the associatedb-blocking effects of propa-fenone.9,10,12,13Three studies evaluated propafenonein a postcardiac surgery setting. Connolly et al13 dem-onstrated the superiority of propafenone versus pla-cebo (43 vs 0% conversion) and Di Biasi et al14 andLarbuisson et al15 showed that intravenous propa-fenone was more effective than intravenous amioda-rone to acutely restore sinus rhythm after cardiacsurgery. Procainamide is generally considered rela-tively effective to terminate AF (conversion rates of40% to 58%).5,6 Boahene et al16 compared propa-fenone and procainamide in the acute treatment of AFin the presence of ventricular preexcitation. Theyshowed no significant difference in conversion ratesbut reported a better rate control with propafenone.Apart from the present study, no comparative studiesof propafenone and procainamide in treating AF aftercardiac surgery are available. As class Ic drugs aregenerally considered to slow conduction without al-tering refractoriness, one could assume that theywould make reentry and AF more likely to sustain.17

It has been shown, however, that class Ic drugs atten-uate the abbreviation in action potential duration thatnormally results from an increased heart rate.7 Thisresults in tachycardia-dependent atrial refractory pe-riod prolongation, which is important to terminate AF.

Although flecainide has been shown to be veryeffective to terminate AF (even more effective thanpropafenone in a comparative study), we decided touse propafenone in our study because of theb-block-ing effects of this drug and a reported lower incidenceof adverse events.8,18

This present study was a prospective, double-blindcomparison that did not include a placebo group.Because many studies already demonstrated the supe-riority of both drugs compared with placebo and,because we believed that the study patients shouldreceive an active drug, it was decided to leave out theplacebo group. Most of the patients in both treatment

TABLE I Patient Characteristics

Propafenone(n 5 29)

Procainamide(n 5 33)

Age (yrs) 67 6 8 66 6 7Men/women 8/21 12/21Type of surgery

CABG 19 23AVR 5 3MVR 2 3Combined CABG/AVR orMVR

3 3

Systolic BP at entry (mm Hg) 120 6 13 122 6 15Heart rate at entry 104 6 23 114 6 23Hour after operation 83 6 52 93 6 70Duration of AF (h) 4 6 7 5 6 5LVEF (%) 52 6 14 47 6 12LA size (mm) 41 6 7 42 6 8Concomitant drugsDigoxin 13 19b blocker 11 14Calcium antagonist 6 6

AVR 5 aortic valve replacement; BP 5 blood pressure; LA 5 left atrium;LVEF 5 left ventricular ejection fraction; MVR 5 mitral valve replacement.

346 THE AMERICAN JOURNAL OF CARDIOLOGYT VOL. 84 AUGUST 1, 1999

arms were pretreated with rate-controlling drugs in-troducing biases in the interpretation of the effects ofthe study drugs on the ventricular response during AF.Because the use of those drugs was comparable inboth groups and the administration of these drugs iscommon practice in treating postoperative AF, we stillthink that the different effects on rate response withthe 2 study drugs are important to report. It has neverbeen shown, however, thatb blockers, calcium antag-onists, or digoxin have any effects on cardioversion inpatients with AF.

Thus, intravenous propafenone is superior toprocainamide to achieve rapid cardioversion and abetter rate control of atrial fibrillation after car-diac surgery. Moreover, the incidence of symptom-atic arterial hypotension is lower with propafenonetreatment.

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variables on risk of supraventricular tachycardia after coronary artery bypass.J Thorac Cardiovasc Surg1991;101:56–65.3. Creswell LL, Schuessler RB, Rosenbloom M, Cox JL. Hazards of postoper-ative atrial arrhythmias.Ann Thor Surg1993;56:539–549.4. Ommen SR, Odell JA, Stanton MS. Atrial arrhythmias after cardiothoracicsurgery.N Engl J Med1997;336:1429–1434.5. Lima JJ, Goldfarb AL, Conti DR, Golden LH, Bascomb BL, Benedetti GM,Jusko WJ. Safety and efficacy of procainamide infusions.Am J Cardiol1979;43:98–105.6. Halpern SW, Ellrodt G, Singh BN, Mandel WJ. Efficacy of intravenousprocainamide infusion in converting atrial fibrillation to sinus rhythm.Br Heart J1980;44:589–595.7. O’Hara G, Villemaire C, Talajic M, Nattel S. Effects of flecainide on the ratedependence of atrial refractoriness, atrial repolarization and atrioventricular nodeconduction in anesthetized dogs.J Am Coll Cardiol1992;19:1335–1342.8. Suttorp MJ, Kingma JH, Jessurun ER, Lie-A-Huen L, van Hemel NM, Lie KI.The value of class Ic antiarrhythmic drugs for acute conversion of paroxysmalatrial fibrillation or flutter to sinus rhythm.J Am Coll Cardiol1990;16:1722–1727.9. Fresco C, Proclemer A, Pavan A, Buia G, Vicentini A, Pavan D, Morgera T.Intravenous propafenone in paroxysmal atrial fibrillation: A randomized, place-bo-controlled, double-blind, multicenter clinical trial.Clin Cardiol 1996;19,5:409–412.10. Bellandi F, Cantini F, Pedone T, Palchetti R, Bamoshmoosh M, Dabizzi RP.Effectiveness of intravenous propafenone for conversion of recent-onset atrialfibrillation: a placebo-controlled study.Clin Cardiol 1995;18,11:631–634.11. Vita AV, Friedman PL, Cantillon C, Antman EM. Efficacy of intravenouspropafenone for the acute management of atrial fibrillation.Am J Cardiol1989;63:1275–1278.12. Bianconi L, Boccadamo R, Pappalardo A, Gentile C, Pistolese M. Effective-ness of intravenous propafenone for conversion of atrial fibrillation and flutter ofrecent onset.Am J Cardiol1989;64:335–338.13. Connolly SJ, Mulji AS, Hoffert DL, Davis C, Shragge BW. Randomizedplacebo-controlled trial of propafenone for treatment of atrial tachyarrhythmiasafter cardiac surgery.J Am Coll Cardiol1987;10:1145–1148.14. Di Biasi P, Scrofani R, Paje A, Cappiello E, Mangini A, Santoli C. Intrave-nous amiodarone versus propafenone for atrial fibrillation and flutter after cardiacoperation.Eur J Cardiothorac Surg1995;10:587–591.15. Larbuisson R, Venneman I, Stiels B. The efficacy and safety of intravenouspropafenone versus intravenous amiodarone in the conversion of atrial fibrillationor flutter after cardiac surgery.J Cardiothorac Vasc Anesth1996;10:229–234.16. Boahene KA, Klein GJ, Yee R, SharmaAD, Fujimura O. Termination of acuteatrial fibrillation in the Wolff-Parkinson White syndrome by procainamide andpropafenone: importance of atrial fibrillatory cycle length.J Am Coll Cardiol1990;16:1408–1414.17. Zipes DP. Genesis of cardiac arrhythmias. In: Braunwald E, ed. HeartDisease, 3rd ed. Philadelphia: WB Saunders,1988:581–620.18. Suttorp MJ, Kingma JH, Lie-A-Huen L, Mast EG. Intravenous flecainideversus verapamil for acute conversion of paroxysmal atrial fibrillation or flutter tosinus rhythm.Am J Cardiol1989;63:693–696.

FIGURE 1. Percentage ofpatients converted to sinusrhythm after start of druginfusion. After 15 minutes,59% of patients receivingpropafenone versus 18% ofpatients on procainamidewere in sinus rhythm. Thecardioversion rate was notsignificantly different in bothgroups after 1 hour (76%propafenone patients vs61% procainamide patients).

TABLE II Side Effects

Propafenone(n 5 29)

Procainamide(n 5 33)

Hot flushes 1Hypotension (,100 mm Hg) 2 9*Nausea 3 2Bronchospasm 1Junctional escape rhythm 2 2

*p ,0.05.

BRIEF REPORTS 347