A multicentre, double-blind randomized crossover comparative study on the efficacy and safety of dofetilide vs sotalol in patients with inducible sustained ventricular tachycardia and ischaemic heart disease

Abstract

Background Antiarrhythmic drugs are still used for the treatment of ventricular tachyarrhythmias, in combination with implantable cardioverter-defibrillators or without them.Aim of the study In a double-blind randomized crossover design, the short-and long-term efficacy and safety of oral dofetilide or oral sotalol were compared in 135 patients with ischaemic heart disease and inducible sustained ventricular tachycardia. MethodsThe inducibility of ventricular tachycardia was determined by programmed electrophysiological stimulation at baseline. Patients were then blindly randomized to receive either oral dofetilide 500 g twice daily or oral sotalol 160 mg twice daily, for 3 to 5 days. Suppression of inducible ventricular tachycardia on the drug was then assessed by programmed electrophysiological stimulation. After a wash-out period of at least 2·5 days, the patients received the alternative treatment for 3 to 5 days. Suppression of inducible ventricular tachycardia on the alternate drug was again determined by programmed electrophysiological stimulation. Selection of long-term treatment was allocated blindly according to programmed electrophysiological stimulation results.Results During the acute phase, 128 patients received both dofetilide and sotalol. Sixty-seven patients were responders to either drug. Forty-six patients (35·9%) were responders to dofetilide compared with 43 (33·6%) to sotalol (P=ns). Only 23 patients responded to both dofetilide and sotalol. Adverse events, deemed to be treatment related, were seen in 2·3% of patients receiving dofetilide and 8·6% of patients receiving sotalol (P=0·016). Three patients on dofetilide had torsade de pointes. Two patients receiving sotalol died during the acute phase (one was arrhythmic death, and the other was due to heart failure). During the long-term phase, two of 42 patients (4·8%) receiving dofetilide and three of 27 patients (11·1%) receiving sotalol withdrew from treatment due to lack of efficacy. Overall, during the long-term phase, 23·8% of the patients receiving dofetilide and 37·0% of the patients receiving sotalol, withdrew from treatment with a similar pattern of withdrawals for the two drugs.Conclusion Dofetilide was as efficacious as sotalol in preventing the induction of sustained ventricular tachycardia. There was no concordance in the response rate in two-thirds of the patients. Dofetilide was significantly better tolerated during the acute phase than sotalol. Both dofetilide and sotalol were well tolerated during the long term with no statistically significant difference in the adverse events.

Optimal antiarrhythmic drug therapy for electrical storm

“…In another study of patients with ICD for secondary prevention of SCD, sotalol (at 80 to 160 mg twice per day) reduced the frequency of shocks per year from 3.89 per year to 1.43 per year, regardless of ejection fraction[83]. In a double-blind study that included patients with sustained VT induced by programmed electrical stimulation at baseline, 34% of patients placed on sotalol (160 mg twice a day) were unable to have VT induced after sotalol loading[84]. Over the subsequent year of follow-up on 26 patients, 1 patient had sustained VT and another patients was felt to have arrhythmic death from VF[84].…”

“…In a double-blind study that included patients with sustained VT induced by programmed electrical stimulation at baseline, 34% of patients placed on sotalol (160 mg twice a day) were unable to have VT induced after sotalol loading[84]. Over the subsequent year of follow-up on 26 patients, 1 patient had sustained VT and another patients was felt to have arrhythmic death from VF[84]. These accumulated data support the current recommendation that sotalol can be helpful in the treatment for sustained ventricular tachyarrythmias unresponsive to β-blockers[30].…”

“…Long term side effects remain a limitation of the medication, as 18–37% of patients stop sotalol within 1 year73,[84]. In follow-up monitoring, sotalol has been implicated in 17% of the reported cases of drug-induced polymorphic VT85,[86].…”

Modern management of arrhythmias

“…Initial studies suggest that it is as effective as sotalol and better tolerated. 48 VT and VF in the structurally normal heart Although the vast majority of cases of VT and VF occur in the setting of impaired left ventricular function, a number of conditions are recognised that cause these arrhythmias in the apparently structurally normal heart. It is important to recognise these arrhythmias as they may be precipitated by certain drugs, may be inherited, or may be amenable to catheter ablation.…”

Efficacy and Safety of Dofetilide in the Treatment of Frequent Ventricular Tachyarrhythmias After Amiodarone Intolerance or Failure

“…Dofetilide, a selective I kr -blocking agent, was as efficacious as sotalol in preventing the induction of sustained VT in patients with ischemic heart disease in 1 study (3). Dofetilide appears to be safe, as the mortality rate was not increased with dofetilide in patients with recent myocardial infarction and impaired left ventricular function (4).…”