Pure class III agents for prevention of sudden cardiac death

The results of clinical trials in postmyocardial infarction patients using type I antiarrhythmic drugs have been disappointing. There was optimism that I_Kr blockers might result in a reduction in sudden cardiac death in postinfarct population. Four trials are reviewed here, and the results are variable. The four drugs reviewed - d,l-sotalol, d-sotalol, dofetilide, and azimilide - all share I_Kr-blocking properties. In addition, d,l-sotalol is a beta-blocker and azimilide is an I_Ks blocker. The primary uses of d,l-sotalol, dofetilide, and, if approved, azimilide are currently for treatment of atrial fibrillation. Thus, the mortality trials reviewed here are primarily used as support of safety in high-risk patients, because none has achieved a mortality reduction in postinfarction patients. These trials play pivotal roles for regulatory approval of these drugs for use in atrial fibrillation.