vernakalant and Drug-Related-Side-Effects-and-Adverse-Reactions

The usual aim of treatment for patients with symptomatic paroxysmal or recent-onset atrial fibrillation, including after cardiac surgery, is to slow the heart rate. Electrical and drug (amiodarone) cardioversion are other options. Vernakalant, an antiarrhythmic drug, has been authorised in the European Union for rapid reduction of recent-onset atrial fibrillation. It is only available in an injectable form. Vernakalant has not been compared in clinical trials with treatments slowing the heart rate, or with electrical cardioversion. The only available comparison with another antiarrhythmic agent is a clinical pharmacology study versus amiodarone, a slow-acting drug, based on the rate of cardioversion at 90 minutes in 240 patients. As expected, given the brief observation period, the rate was significantly higher with vernakalant (51.7% versus 5.2%). During clinical evaluation, 6 deaths occurred in the vernakalant groups versus none in the other groups (placebo or amiodarone). The main adverse effects of vernakalant are cardiac arrhythmias (ventricular arrhythmia, torsades de pointes, bradycardia) and severe hypotension. Altered taste, sneezing, paraesthesia, nausea and pruritus were frequent, and respiratory and neuropsychological effects were also reported. A trial in atrial flutter was interrupted when cases of cardiogenic shock occurred. Interactions are to be expected with drugs that prolong the QT interval, and also with drugs that lower the heart rate or the blood potassium concentration. In practice, it is better to continue to use amiodarone for drug cardioversion and to avoid using vernakalant.

Topics: Anisoles; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Clinical Trials as Topic; Clinical Trials, Phase IV as Topic; Drug Approval; Drug-Related Side Effects and Adverse Reactions; Humans; Hypotension; Pharmacovigilance; Pyrrolidines

Atrial fibrillation, which is associated with a worsening of congestive heart failure symptoms, an increased rate of stoke, and increased mortality, is still difficult to treat. New therapies must not only increase effectiveness, but also have to have an improved safety profile, in order to avoid sodium channel block in the ventricle of older patients with atrial fibrillation, and also prevent electrical and morphological remodeling. Dronedarone is less effective compared to amiodarone, but has a better side effect profile which leads to fewer discontinuations of treatment. The atrial ion channels are specifically blocked by a number of prospective antiarrhythmic substances. The most advanced is the testing of vernakalant (RSD1235), which primarily suppresses the I(Kur) current. Ranolazine is a new antianginal substance which influences the atrial ion channels and leads to a significant reduction of atrial and more specifically ventricular tachyarrhythmias. A number of other drugs are in development. They will lead to a better understanding of which form of atrial fibrillation can be best treated with which antiarrhythmic agent.

Topics: Acetanilides; Aged; Amiodarone; Animals; Anisoles; Anti-Arrhythmia Agents; Atrial Fibrillation; Dronedarone; Drug-Related Side Effects and Adverse Reactions; Drugs, Investigational; Electrocardiography; Heart Atria; Heart Failure; Heart Ventricles; Humans; Piperazines; Potassium Channels; Pyrrolidines; Ranolazine; Sodium Channels; Stroke