A 40-year-old drug is still viable

Spironolactone (Searle’s Aldactone) has been on the market since 1960 and costs as little as 10 cents a day. (See CHF Disease Management, September 1999, p. 102.) The drug suppresses aldosterone, a steroidal hormone secreted by the adrenal glands that retains sodium, depletes potassium, and stiffens the tissues of the heart and blood vessels, worsening other cardiovascular risks.

Aldosterone also elevates norepinephrine, stressing the heart. Spironolactone was generally abandoned when ACE inhibitors — thought to work against aldosterone as well — came on the scene in the 1970s, and the standard regimen for severe heart failure became ACE inhibitors, diuretics, and others. But then researchers found that after several months of treatment with ACE inhibitors, their effect is transitory, and aldosterone returns at least to its previous level. Searle had not promoted Aldactone’s use in the United States in 20 years, but then decided to fund the study referenced above. (See related story, p. 10.)

Pitt and associates tested the hypothesis that adding an aldosterone antagonist (25 mg spironolactone) to traditional heart failure therapy with ACE inhibitors would reduce mortality. The trial was designed to last for up to three years, but was halted a year early because the benefits to patients were unmistakable.

According to a recent article in U.S. News & World Report,1 in 1994, a study published in the New England Journal of Medicine surveyed 1,211 doctors about their use of heart attack drug therapies that had been in the medical literature for up to a decade. Almost 22% of cardiologists, 37% of internists, and 47% of family practitioners were not using one or more of the beneficial drugs — and 5% to 26% were using other drugs that had been largely discredited.

This fall, researchers at Searle will begin testing a drug called Eplerenone that may prove to reduce the side effects of spironolactone because about 10% of men using it experience gynecomastia or impaired sex drive. Hyperkalemia occurred in 10% of study participants as well.

Reference

1. Comarow A. New hope from a 40-year-old drug: Deaths from heart failure cut by 30 percent. U.S. News & World Report: Aug. 2, 1999: News You Can Use.