SIR—Despite advances in treatment, survivors of a myocardial infarction with left ventricular dysfunction are at an increased risk for sudden cardiac death, for which there is limited effective therapy. When the SWORD trial was designed, 1 the evidence indicated that sodium channel blocking antiarrhythmic drugs were harmful in these highrisk patients. β-adrenergic blocking drugs were helpful, but as documented in many studies, were used infrequently, perhaps because of impaired ventricular function. Drugs that prolong ventricular repolarisation (class III) were unproven, but preliminary evidence suggested potential benefit without apparent harm. Amiodarone was the prototype for this class, but it clearly had complex actions with difficult pharmacokinetics and important potential toxicity. Although the usefulness of amiodarone may be related to its multiple activities, a major benefit was thought to be related to its blockade of potassium channels in cardiac cells. Consequently, research interest focused on the identification and development of less complex, better tolerated drugs with this specific activity.

As we stated in our report, the SWORD trial tested the hypothesis that prolongation of action potential duration with a pure potassium-channel blocker could reduce all cause mortality in patients with previous myocardial infarction and ventricular dysfunction at increased risk of death. d-sotalol had substantial supportive preclinical and clinical experience as compared with similar compounds. Nearly 1000 patients had received the drug. Preliminary evidence showed antiarrhythmic efficacy with a low incidence of torsades de pointes, even in patients with life-threatening ventricular arrhythmias. Although we did not do a pilot study, we did do a run-in analysis on the first 500 patients, paying particular attention to the incidence of torsades de pointes and QT interval prolongation, and did not find any indication of adverse effects which would make us consider stopping the trial. This should not be a surprise because, on the basis of the Cardiac Arrhythmia Pilot Study, 2 a small preliminary trial in postmyocardial infarction high-risk patients may not be useful in predicting efficacy or safety. Thus, the SWORD trial was a carefully planned, well executed, multinational study which was the largest of its kind. d-sotalol was an appropriate choice to explore an hypothesis that offered the promise of a new and important therapy. Although the results were not those that were anticipated, they were convincing. Once again we should recognise our limited knowledge of the mechanisms leading to sudden cardiac death, and the importance of double-blind, randomised, placebo-controlled, clinical trials testing the effect of antiarrhythmic therapy on all-cause mortality. We agree with Tan that there should not be a moratorium on antiarrhythmic drug trials. Our treatment decisions need to be based on objective medical evidence. In primary prevention trials of sudden death with prophylactic antiarrhythmic drug therapy, an appropriate risk/benefit assessment can best be achieved by use of randomised, placebo-controlled trials, such as SWORD, which enrol presumably high-risk patients under the supervision of a safety committee guided by prospectively defined stopping rules.