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What do we know about vernakalant?

What do we know about vernakalant?

At Europe AF, 21–22nd November, London, UK, John Camm (professor of clinical cardiology, St George’s University, London, UK) reviewed the available data for vernakalant (Brinavess; MSD, Cardiome Pharma)

He said: “Vernakalant is highly effective at cardioversion of atrial fibrillation, it is relatively ineffective at terminating atrial fibrillation of more than a few days’ duration, and it is completely ineffective for atrial flutter.”

He explained that the ACT series of phase III trials (with ACT standing for “Atrial Arrhythmia Conversion Trial”) showed the efficacy of vernakalant compared with placebo (Savelieva et al, Europace 2008; 10:647–65). “Concerning atrial fibrillation of fewer than seven days’ duration, the effect of vernakalant was remarkably consistent-between 47% and 53% of patients were converted to sinus rhythm. If we look at patients with atrial fibrillation duration of three to 72 hours, this figure was much higher (58% in ACT I and 74% in ACT III). However, in atrial fibrillation of longer duration (eight to 45 days) or in atrial flutter, vernakalant was ineffective.” He added that an exception to this was ACT II, which was a post-operative study that found more spontaneous termination of atrial fibrillation than the other studies.

According to a pooled analysis of the ACT I and III studies, 97.2% of patients who were converted to sinus rhythm following treatment with vernakalant were still in sinus rhythm 24 hours after treatment compared with 83.3% of patients who were treated with placebo. Camm said that the maintenance of sinus rhythm was important because “there is not much point terminating atrial fibrillation if within a minute or two, the atrial fibrillation resumes”.

Dysgeusia, sneezing, paraesthesia, and nausea were four of the five most common adverse even seen with vernakalant. Camm said that they were all “probably part of a central nervous syndrome that is produced by this drug.” Hypotension was the fifth most common adverse event, which Camm described as being an “important event” that was frequently seen with vernakalant in patients who were poorly hydrated. He added that in contrast to the other four common adverse events, which occurred relatively soon after the vernakalant treatment was administered and were of relatively short duration, hypotension occurred later and tended to last for longer.

Camm also reviewed the AVRO study (Camm et al, J Am Coll Cardiol 2011; 57: 313–21), which is the only head-to-head comparison of vernakalant with another antiarrhythmic (amiodarone). He said: “The results were simple and straightforward. The effect was consistent with what was seen in the other studies of vernakalant-atrial fibrillation was terminated in 52% of patients-and the speed of the conversion was very prompt.” This study also showed that vernakalant was superior to amiodarone at acute conversion of recent-onset atrial fibrillation.

Looking to the future of vernakalant, although approved in Europe, more data are needed before it can be approved in America. For this reason, the ACT V study is currently underway and its primary outcome measures are a composite of adverse events (such as hypotension) occurring with the first two hours after treatment and the successful conversation to sinus rhythm within the first 90 minutes of first exposure to the drug. Camm explained: “It was due to finish in May 2011 but is on hold because of the death of one patient.”

Summing up the evidence for vernakalant, Camm said the drug was probably cost effective compared with electric cardioversion despite there being no studies at present to show this. “It is probably not cost effective compared with flecainide or propafenone. But, the use of flecainide and propafenone is restricted to patients without structural heart disease.”