Keck School of Medicine of USC researchers have helped bring to light a new, successful therapy for patients with heart failure.
Published in the Nov. 11 issue of the New England Journal of Medicine, the highly publicized study findings showed that a combination of medications dramatically reduced death and slowed disease progression in blacks with serious heart disease.
The medications – hydralazine and isosorbide dinitrate – worked so well together that investigators halted their multi-center trial early so the more than 1,000 study participants could all be put on the same treatment.
The drug combination reduced the death rate by 43 percent in study patients in the first year.
The study, called the African American Heart Failure Trial, or A-HeFT, involved patients from 161 centers across the nation.
For Uri Elkayam, professor of medicine in the Keck School, director of the Heart Failure Program and principal investigator of A-HeFT at USC, the study was a success for two reasons: He and his Keck School colleagues not only contributed patients to A-HeFT, but a decade ago, they were the first to show that hydralazine prevented nitrate tolerance, a phenomenon that results in an early attenuation of nitrates’ effects.
“It is gratifying to see our research eventually result in a therapy that we always believed would substantially boost the treatment of heart failure,” Elkayam said.
The results of the study are particularly impressive since hydralazine and isosorbide demonstrate reduced mortality beyond effective standard therapy for heart failure, he said.
Hydralazine and isosorbide dinitrate are existing drugs that cardiologists have used to treat numerous heart conditions. Unfortunately, patients often become resistant to the beneficial effects of isosorbide dinitrate and other nitrate drugs, such as nitroglycerine.
In December 1995, Elkayam and his USC research team published a pilot study in the Journal of the American College of Cardiology showing that hydralazine seemed to help patients with heart failure from becoming resistant to nitroglycerin.
Today, researchers still are not sure why the drugs work well together, but they suspect that nitrates may work by creating nitric oxide, which causes vasodilation – the dilation of blood vessels – and helps protect the cardiovascular system.
As an antioxidant, hydralazine might reduce oxidative stress and prevent nitric oxide inactivation.
Researchers restricted participants in A-HeFT to black patients because blacks have a disproportionate rate of heart failure and other cardiovascular disease and because previous research demonstrated that black patients responded well to these drugs.
“Although the study focused on African American patients, multiple studies by our group and other research groups have previously shown a beneficial effect of these drugs on the hemodynamics, ability to exercise and function of the heart in Caucasians and Hispanic patients with heart failure,” Elkayam said.
“For these reasons, I believe that the A-HeFT therapy will be useful for non-black patients as well.”
About five million Americans have some form of heart failure, which has treatments, but no cure. More than 50 percent of patients die within five years of diagnosis.
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