Rapid cardioversion of atrial fibrillation nova-Vernakalant

Vernakalant atrium is a selective ion channel mixed sodium / potassium channel blocker, by prolonging the atrial refractory period, the rate-dependent ion channel block to extend the atria, but the ventricular repolarization no significant effect. The drug in humans rapid onset, half-life of 3-5h. ESC guidelines in 2010 after the announcement, Vernakalant has been approved for continuous AF ≤ 7 days non-surgical patients, or the occurrence of AF after cardiac surgery ≤ 3 days continued rapid cardioversion in patients with sinus rhythm. About Vernakalant has announced CRAFT, ACT I-IV, AVRO, Scene 2 and many other clinical studies.
    1.Vernakalant effectiveness
    In the Atrial arrhythmia Conversion Trials (ACT) III-IV of the study were randomly divided into a first group of patients receiving vernakalant 3 mg / kg vernakalant intravenously 10 minutes, after 15 minutes of observation it if necessary and then given 2 mg / kg vernakalant intravenous injection 10 minutes. The proportion of patients enrolled patients was 68% male, mean age 63 years, cardioversion to normal sinus rhythm is the study's primary endpoint.
    ACT series of studies showed that: Compared with placebo, for sustained atrial fibrillation ≤ 7 days, vernakalant group has a higher cardioversion rate (51.7% vs 4%). Successful cardioversion, with time and more in 8-11 minutes, and 75-82% of patients given vernakalant when you can first cardioversion sinus rhythm.
    Amiodarone group received infusion of 5 mg / kg amiodarone for 60 minutes, followed by an additional 60 minutes and then received 50 mg maintenance infusion. Compared with amiodarone, administered 90 minutes later, 51.7% of vernakalant patients conversion to sinus rhythm, but amiodarone group cardioversion rate was 5.2% (p <0.0001); administered 4 hours After, vernakalant group cardioversion was 54.4%, amiodarone group was 22.6% (P <0.0001). Meta-analysis shows: vernakalant 90 minutes fast sinus rhythm cardioversion placebo or amiodarone validity is 8.4 times (95% CI 4.4-16.3), without increasing the incidence of serious adverse events (RR 0.91; 95% CI 0.6-1.36).
    In a subgroup analysis, for people with different underlying diseases (such as ischemic heart disease and hypertension) in patients with paroxysmal atrial fibrillation, Vernakalant still valid. 274 cases of ischemic heart disease (41% occurred in previous myocardial infarction) in, Vernakalant of cardioversion was 45.7%, with non-ischemic heart disease cardioversion rate is very close (47.3%). And no increase in blood pressure, bradycardia and ventricular arrhythmias and other adverse cardiovascular event rates. Accepted Vernakalant after cardioversion, 95% of patients with atrial fibrillation can be maintained sinus rhythm more than 24 hours. 76% of Vernakalant group of patients while taking β-blockers, calcium channel blockers or digoxin, 24% of Vernakalant group of patients receiving other anti-arrhythmic drug therapy, no increased incidence of adverse events.

For paroxysmal atrial fibrillation after cardiac surgery patients, Vernakalant of cardioversion was 47% (14% in the placebo group), the average time was 12 minutes turn sinus. For the last> 7 days or persistent atrial fibrillation atrial flutter, Vernakalant largely ineffective cardioversion rate of 8.6-12.7%.

    Security 2.Vernakalant

    Vernakalant most common adverse reactions are dysgeusia (30%), sneezing (16%), paresthesia (10%) and nausea (9%), and more symptoms disappear in 5-15 minutes. Vernakalant does not increase the incidence of serious cardiovascular events. A transient hypotension incidence of 5-7%, blood pressure more than 15-20 minutes to return to normal. Vernakalant hypotension occurred in patients with heart failure (16.1%), 2.9% of patients therefore disabled Vernakalant. Compared with placebo, Vernakalant does not increase the incidence of ventricular arrhythmias. However, in patients with heart failure, Vernakalant will bring more than the placebo group frequent PVCs or nonsustained ventricular tachycardia (7.3% vs. 1.6%), and may cause QTc prolongation (20-25ms) and widened QRS 8ms.

    Vernakalant disabled in hypotension (systolic blood pressure <100mmHg), 30 days of new-onset ACS, NYHA Class III-IV heart function, severe aortic stenosis and QTc prolongation (> 440 ms) of patients. Due to the increased incidence of hypotension, Vernakalant caution in NYHA functional class I-II patients with atrial fibrillation. Due to lack of evidence based medicine, Vernakalant should be avoided in patients with atrial fibrillation LVEF ≤ 35.

2012 ESC AF guidelines recommend: preferred drugs for cardioversion of atrial fibrillation in patients with sinus rhythm, with no or only mild case of structural heart disease, it is recommended intravenous flecainide, propafenone, ibutilide and Vernakalant (I recommend class, A-level evidence); For sustained atrial fibrillation ≤ 7 天 and there is moderate structural heart disease (not associated with systolic blood pressure <100mmHg, 30 days, ACS, NYHA functional Class III-IV heart or main severe arterial stenosis, etc.) can be considered intravenous Vernakalant, caution in NYHA functional class I-II patients with atrial fibrillation (IIb class recommendation, B level of evidence); AF sustained ≤ 3 days after cardiac surgery patients, but also consider intravenous Vernakalant (IIb class recommendation, B level of evidence).