CLINICAL SAFETY PROFILE OF SOTALOL IN THE TREATMENT OF ARRHYTHMIAS

The safety of sotalol was evaluated in 3,257 patients treated for card iac arrhythmias in double-blind and open-label clinical trials that su pport United States registration of the drug. In this composite popula tion, 80% of patients had structural heart disease and 42% had life-th reatening ventricular arrhythmias, i.e., ventricular tachycardia (VT) or fibrillation (VF). Proarrhythmia was reported in 141 patients (4.3% ). Of these, 78 (2.4%) had torsades de pointes and 26 (0.8%) had susta ined VT or VF. The overall incidence was higher in patients treated fo r sustained VT or VF (6.5%). In these patients, serious proarrhythmia was predominantly torsades de pointes (4.1%) and was more prevalent in patients with congestive heart failure and low ejection fraction. Tor sades de pointes was observed early in the course of treatment, and it s occurrence was related to dose. The overall mortality in patients tr eated wit sotalol was 4.3% (139 patients); in patients with life-threa tening arrhythmias, cardiac mortality was 4.8%. In only 27 patients (0 .8%) was the death thought to be potentially drug-related. The deaths were not related to dose. Data from a previously reported placebo-cont rolled postmyocardial infarction trial indicated no significant differ ence in mortality between sotalol and placebo. Heart failure was repor ted in 3.3% of patients and was most prevalent in those with a previou s history of congestive heart failure, cardiomyopathy, or structural h eart disease. The occurrence of heart failure was unrelated to dose or time on drug; in more than half of the patients, sotalol treatment wa s continued. On average, there was no decrease in ejection fraction. R eported adverse drug experiences were typical of beta blockers and res ulted in discontinuation of the drug in 18% of patients. There was no evidence of organ toxicity or interaction with concomitant therapy. As an antiarrhythmic agent, sotalol is generally well tolerated and has a favorable profile relative to that reported for many other agents.