Diuretic Use, Progressive Heart Failure, and Death in Patients in the DIG Study

Background: Nonpotassium-sparing diuretics (NPSDs), have been associated with increased sudden cardiac death (SCD) and progressive heart failure (HF) death in HF patients. Methods and Results: In 6797 Digitalis Investigation Group study patients, risk ratios were calculated for death, cardiovascular death (CVD), death from worsening HF, SCD, and HF hospitalization among those taking a potassium-sparing (PSD), NPSD, or no diuretic. Compared with not taking diuretic, risk of death (relative risk [RR] 1.36, 95% confidence interval [CI] 1.17-1.59, P < .0001), CVD (RR = 1.38, 95% CI 1.17-1.63, P = .0001), progressive HF death (RR = 1.41, 95% CI 1.06-1.89, P = .02), SCD (RR = 1.67, 95% CI 1.23-2.27, P = .001), and HF hospitalization (RR = 1.68, 95% CI 1.41-1.99, P < .0001) were increased with NPSD. There was no significant difference in any end point for patients taking only PSD compared to no diuretic. PSD only subjects were less likely than NPSD subjects to be hospitalized for HF (RR = 0.71, 95% CI 0.52-0.96, P = .02). Conclusion: NPSDs are associated with increased risk of death, CVD, progressive HF death, SCD, and HF hospitalization. A randomized trial is needed to assess the role of NPSDs versus PSDs in HF patients.