Benefit in adding an epithelial sodium channel inhibitor to a thiazide diuretic.

Supplementing diuretic therapy with a drug that conserves potassium reduces the overall risk of cardiac mortality as well as the risk of sudden cardiac death (SCD), according to a meta-analysis conducted by researchers at Vanderbilt University in Nashville.

They found three controlled clinical trials in which an epithelial sodium channel (ENaC) inhibitor was combined with hydrocholorothiazide. These studies evaluated 5,761 patients for 32,657 patient-years. Participants were 60-84 years old (median 70-76). Patients receiving the dual regimen experienced a 40% decrease in SCD risk and a 41% decrease in overall cardiac mortality risk compared with patients who received diuretics plus placebo, the investigators reported in the Journal of the American Society of Hypertension (2008;2:355-365).

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“It was very striking,” observed senior author John A. Oates, MD, professor of medicine and a hypertension specialist at Vanderbilt.

A second meta-analysis of 16 trials that tested thiazide alone found no significant reduction in coronary mortality or SCD. NIH guidelines recommend using a thiazide diuretic alone as the initial therapy for hypertension. An update is expected next year. “The recommendations can now be re-examined in light of these new findings,” said Dr. Oates, whose research was partially funded by the National Institute of General Medical Sciences.

Pending further studies to determine the mechanism that may be at work and whether the combination therapy is appropriate for younger patients, “it’s time to add ENaC inhibitors to thiazides as recommended first-line treatment for hypertension in the elderly,” Dr. Oates said.