A new meta-analysis suggests that supplementing diuretic hypertension therapy with a drug that conserves potassium sharply reduces fatal heart attacks and sudden cardiac death (SCD).

Researchers found three controlled clinical trials in which an epithelial sodium channel (ENaC) inhibitor was combined with hydrochlorothiazide (HCTZ). These studies evaluated 5,761 patients for 32,657 patient-years. Participants were aged 60-84 years. The data found a 40% reduction in SCD (odds ratio [OR] 0.60) and in overall cardiac mortality (OR 0.59) among treated patients as compared with controls (J Am Soc Hypertens. 2008;2:355-365.e2).

“It was striking,” notes senior author John A. Oates, MD, a professor of medicine and hypertension specialist at Vanderbilt University Medical Center in Nashville.

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A second meta-analysis of 16 trials that tested thiazide alone found no significant reduction in coronary mortality and a 27% increase in SCD. Although that percentage seems high, it was not statistically significant, Dr. Oates explains, but “it was going in the direction in which you don’t want to go.”

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,” says Dr. Oates, whose research was funded in part by the National Institute of General Medical Sciences.

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