Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction

Background Left ventricular dysfunction after myocardial infarction is associated with an increased risk of death. Other studies have suggested that a potassium-channel blocker might reduce this risk with minimal adverse effects. We investigated whether d-sotalol, a pure potassium-channel blocker with no clinically significant beta-blocking activity, could reduce all-cause mortality in these high-risk patients. Methods Patients with a left ventricular ejection fraction of 40% or less and either a recent (6-42 days) myocardial infarction or symptomatic heart failure with a remote (>42 days) myocardial infarction were randomly assigned d-sotalol (100 mg increased to 200 mg twice daily, if tolerated) or matching placebo twice daily. Findings After 3121 of the planned 6400 patients had been recruited, the trial was stopped. Among 1549 patients assigned d-sotalol, there were 78 deaths (5.0%) compared with 48 deaths (3 1%) among the 1572 patients assigned placebo (relative risk 165 [95% CI 1.15-2.36], p=0.006). Presumed arrhythmic deaths (relative risk 1.77 [1.15-2.74], p=0.008) accounted for the increased mortality. The effect was greater in patients with a left ventricular ejection fraction of 31-40% than in those with lower (less than or equal to 30%) ejection fractions (relative risk 4.0 vs 1.2, p=0.007). Interpretation Among the 1549 patients evaluated, administration of d-sotalol was associated with increased mortality, which was presumed primarily to be due to arrhythmias. The prophylactic use of a specific potassium-channel blocker does not reduce mortality, and may be associated with increased mortality in high-risk patients after myocardial infarction.