Quinidine plus verapamil vs. quinidine alone to prevent recurrences of atrial fibrillation

Henrique H. Veloso

Hospital da Venerável Ordem Terceira da
Penitência Rio de Janeiro
Rio de Janerio, Brazil
E-mail address: hhorta{at}cardiol.br

Angelo A.V. de Paola

Federal University of São Paulo
São Paulo, Brazil
E-mail address: depaola{at}uol.com.br

The excellent PAFAC1 and SOPAT2 trials demonstrated that quinidine, in combination with verapamil, is at least equivalent to sotalol in the prevention of recurrences of atrial fibrillation (AF). The combination of verapamil with quinidine in this setting may be beneficial for several reasons. First, verapamil has the ability of suppressing after depolarizations underlying the onset of torsades de pointes, which justifies the low rate of pro-arrhythmic events observed with quinidine during the follow-up period of these trials.13 Secondly, it has been already demonstrated that the addition of verapamil to Class IC or III antiarrhythmic drugs significantly reduces recurrences of AF,4 an effect that may also occur with quinidine, a Class IA drug. Finally, the concomitant administration of verapamil is also desirable to avoid arrhythmia recurrences with high ventricular rates due to enhanced atrioventricular conduction promoted by the vagolytic effect of quinidine. Despite all these benefits, clinical trials routinely did not use the combination of quinidine with verapamil. Thus, we expected that the PAFAC and the SOPAT trials had explored the clinical effects of this association throughout. These trials clearly presented the efficacy and the pro-arrhythmic complications of antiarrhythmic therapy, but failed in presenting the ventricular rates during recurrences of AF.

Comparing quinidine alone vs. sotalol to prevent arrhythmia recurrences after chemical or electrical cardioversion of AF, we observed that sotalol tended to be associated with more tolerated recurrences when compared with quinidine, which was related to a decrease in ventricular rates during recurrences, from a mean of 98±18 b.p.m. in the baseline recording before conversion to 82±20 b.p.m. during treatment (P=0.02).5 In the quinidine group, ventricular rates tended to increase during recurrence, from a mean of 102±28 b.p.m. in the initial episode to 113±44 b.p.m. (P=0.06). Another randomized trial comparing quinidine alone vs. sotalol also demonstrated that ventricular rate after relapsing into AF was higher in patients treated with quinidine (109 b.p.m.) when compared with patients treated with sotalol (78 b.p.m., P<0.001).6 In this study, patients treated with sotalol were also less symptomatic at the time of relapse when compared with relapsing patients in the quinidine group. Differently from the PAFAC and the SOPAT trials, these previous studies were limited because they did not use trans-telephonic electrocardiographic monitoring to detect asymptomatic or short episodes of paroxysmal arrhythmia.

In conclusion, the results of the PAFAC and the SOPAT trials strongly suggest that the combination of quinidine with verapamil is superior to quinidine alone in patients with AF. The theoretical benefits of this combination when compared with quinidine alone to reduce recurrence rate of AF, avoid pro-arrhythmic events, and control ventricular rates during arrhythmia recurrence should be investigated in a randomized trial.

References

  1. Fetsch T, Bauer P, Engberding R, Koch HP, Lukl J, Meinertz T, Oeff M, Seipel L, Trappe HJ, Treese N, Breithardt G, for the Prevention of Atrial Fibrillation After Cardioversion Investigators. Prevention of atrial fibrillation after cardioversion: results of the PAFAC trial. Eur Heart J 2004;25:1385–1394.[Abstract/Free Full Text]
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  3. van Hemel N. Quinidine rehabilitated and more lessons from the PAFAC and SOPAT anti-arrhythmic drug trials for the prevention of paroxysmal atrial fibrillation. Eur Heart J 2004; 25:1371–1373.[Free Full Text]
  4. de Simone A, de Pasquale M, de Matteis C, Canciello M, Manzo M, Sabino L, Alfano F, di Mauro M, Campana A, de Fabrizio G, Vitale DF, Turco P, Stabile G. Verapamil plus antiarrhythmic drugs reduce atrial fibrillation recurrences after an electrical cardioversion (VEPARAF Study). Eur Heart J 2003;24:1425–1429.[Abstract/Free Full Text]
  5. de Paola AA, Veloso HH, for the SOCESP Investigators. Efficacy and safety of sotalol versus quinidine for the maintenance of sinus rhythm after conversion of atrial fibrillation. Am J Cardiol 1999;84:1033–1037.[CrossRef][ISI][Medline]
  6. Juul-Möller S, Edvardsson N, Rehnqvist-Ahlberg N. Sotalol versus quinidine for the maintenance of sinus rhythm after direct current conversion of atrial fibrillation. Circulation 1990;82: 1932–1939.[Abstract/Free Full Text]




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