Large German study
Quinidine Makes Comeback for Atrial Fibrillation
Verapamil helps neutralize quinidine's proarrhythmic tendencies.
Bruce Jancin
Denver Bureau
BERLIN — Quinidine may be back from the brink.
The venerable class I antiarrhythmic agent has been in strong disfavor since the early 1990s, when a metaanalysis concluded its proarrhythmic effects resulted in increased mortality in treated patients with atrial fibrillation (AF).
Now a large German study indicates that combining quinidine with the calcium channel blocker verapamil neutralizes quinidine's proarrhythmic tendencies while providing surprisingly good long- term efficacy in maintaining sinus rhythm.
The double- blind Prevention of Atrial Fibrillation After Cardioversion (PAFAC) trial involved 761 patients randomized to quinidine plus verapamil or to the class III agent sotalol following successful direct current cardioversion. Last year PAFAC investigators raised eyebrows when they reported an advantage for quinidine/ verapamil in the primary study end point— the 1- year rate of continuous freedom from atrial fibrillation— which was 62% , compared with 50% with sotalol.
The new finding presented at this year's Congress of the European Society of Cardiology is that at 2 years' follow- up, there hasn't been a single additional patient with return of AF in the intervening year. The 2- year freedom from AF in the quinidine/ verapamil group remains steady at 62% .
Indeed, among patients who didn't have a recurrence during their first 4 weeks on quinidine plus verapamil, the likelihood of recurrence during the next 23 months was 10% . Moreover, all nine cases of potentially life- threatening torsades de pointes that occurred during the 2 years were in the sotalol group, reported Dr. Thomas Fetsch, director of the Institute for Clinical Cardiovascular Research, Munich.
“ Quinidine is no longer the bad boy of antiarrhythmic agents, ” he declared.
The difference comes from giving it with verapamil, which suppresses the antiarrhythmic agent's tendency to produce early after- depolarizations. This is probably one of the mechanisms underlying combination therapy's improved safety.
“ I would never recommend giving quinidine alone, ” the cardiologist emphasized.
Another new finding in the Knoll- sponsored PAFAC trial is that two- thirds of all cases of torsades de pointes, one- half of ventricular tachycardias, and all cases of ventricular fibrillation in the 2- year study happened in the first 4 days of therapy, during the loading- dose phase.
PAFAC relied upon a novel means of detecting AF recurrences: an easy- to- use credit card– sized ECG event recorder. Every day, participants were required to telephonically transmit at least one ECG, even if they felt perfectly fine. In this way, PAFAC investigators determined that fully 70% of all AF episodes during the trial were completely asymptomatic.
In addition to the quinidine/ verapamil combination's impressive safety and efficacy, other attractive features include the fact that both drugs are available in relatively low- cost generic versions. Tolerability is very good, as quinidine's tendency to cause diarrhea is canceled by verapamil's proclivity for constipation.
Discussant Dr. Luc Jordaens observed that the combination's long- term efficacy in PAFAC is on a par with that of amiodarone, which most cardiologists consider the most effective antiarrhythmic in AF.
“ I at first glance considered this a funny regimen. I mean, quinidine plus verapamil? But it was effective and superior to sotalol, a drug we've trusted over the years. I think this trial is a real advance in the treatment of atrial fibrillation, ” said Dr. Jordaens of Erasmus University, Rotterdam, the Netherlands.
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