Treatment of elderly hypertensive patients with epithelial sodium channel inhibitors combined with a thiazide diuretic reduces coronary mortality and sudden cardiac death

No reduction in either coronary mortality or sudden cardiac death (SCD) has been demonstrated in overviews of randomized trials of treatment of hypertension with diuretics. An overview was conducted of coronary mortality and SCD in randomized controlled antihypertensive trials in which an epithelial sodium channel (ENaC) inhibitor/hydrochlorothiazide (HCTZ) combination was used. Secondarily, an analogous overview in which thiazide diuretic was used alone was performed. Randomized trials that used an ENaC inhibitor/HCTZ combination (or, alternatively, thiazide diuretic alone) were identified from previous meta-analyses, searches of PubMed, search of the Cochrane Clinical Trials database, and review of publications that addressed the consequences of treating hypertension. Trials in which participants were randomized to either an ENaC inhibitor combined with a thiazide diuretic (or to a thiazide diuretic alone) or to control treatment for at least 1 year and in which coronary mortality was reported were included. Numbers of events in individual trials were abstracted independently by two authors. Significant reductions in both coronary mortality and SCD were observed in the overview of trials in which elderly patients received an ENaC inhibitor/HCTZ combination. The odds ratio (OR) for coronary mortality was 0.59 (95% confidence interval [CI], 0.44 to 0.78) and for SCD was 0.60 (95% CI, 0.38 to 0.94). In contrast, an overview of the trials using thiazide diuretics alone showed no significant reductions of either coronary mortality (OR, 0.94; 95% CI, 0.81 to 1.09) or SCD (OR, 1.27; 95% CI, 0.93 to 1.75). Use of an ENaC inhibitor combined with HCTZ for treatment of hypertension in the elderly results in favorable effects on coronary mortality and SCD.