In addition to the current trial, called EPHESUS, Pitt also led a previous study called RALES that showed the efficacy of spironolactone, another drug that blocks the same hormone system, in reducing death and hospitalization from severe heart failure.

Both eplerenone and spironolactone block the effects of aldosterone, a hormone known to damage heart muscle and, in conjunction with another molecule called angiotensin II, cause blood vessel damage.

The positive clinical results from the two aldosterone-blocking drugs come with some caveats. The use of spironolactone has often led to side effects like hyperkalemia, or high and potentially dangerous levels of potassium, and impotence and breast swelling, or gynecomastia, in men.

The EPHESUS results show no increased incidence of gynecomastia or impotence in the treatment group, reflecting eplerenone's higher level of selectivity for the aldosterone hormone receptors as compared with spironolactone. However, there was an increased incidence of hyperkalemia in the patients on eplerenone, especially those whose kidneys were less able to remove creatinine from the body.

"This hormone is turning out to be more important than anyone thought," says Pitt, who predicts that combining an aldosterone-blocking drug with angiotensin II inhibitor and beta blocker drugs may eventually become a standard treatment for appropriate heart failure patients.

Pitt suggests that the success of eplerenone combined with other drugs in cutting mortality and hospitalization should raise questions about the cost-effectiveness of implanted defibrillators that are being considered for approval by the Centers for Medicare and Medicaid Services for heart failure treatment under Medicare.

Eplerenone, whose trade name is Inspra, is a product of Pharmacia Corporation. Though approved for hypertension, the product is not yet on the market. The EPHESUS study was supported
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Contact: Kara Gavin
kegavin@umich.edu
734-764-2220
University of Michigan Health System
31-Mar-2003