High doses of ACE inhibitors reduce hospitalizations for heart failure

November 11, 1999

DALLAS, Nov. 8 -- Large doses of drugs called ACE inhibitors are more effective than the smaller doses often prescribed to heart failure patients, according to a study that is the first to be released on-line prior to publication in Circulation: Journal of the American Heart Association. The paper will be available on-line beginning November 8 as part of the journal's new Rapid Track publications. It will be published in a December issue of the journal.

Rapid Track publications have been initiated to identify manuscripts reporting results in critical areas of research, especially clinical trials containing results warranting exceptionally rapid review and publication.

Each article so identified will be reviewed within a week, and if accepted, be published online within two weeks and in the print journal within four to five weeks.

ACE (angiotensin-converting enzyme) inhibitors help weak hearts pump blood by blocking the production of a hormone that forces the heart to work harder, leading to a further weakening of the heart. Congestive heart failure is a condition in which the heart cannot pump enough blood to meet the needs of the body's other organs. A number of conditions can lead to congestive heart failure including high blood pressure, a heart attack, a heart muscle disease called cardiomyopathy, atherosclerosis, and congenital heart defects.

"Several treatment guidelines have strongly recommended that physicians prescribe ACE inhibitors to all patients with the most common type of heart failure (left ventricular systolic dysfunction) who can tolerate the drugs," says Milton Packer, M.D., chief, division of circulatory physiology and director of the Center for Heart Failure Research at the College of Physicians and Surgeons, Columbia University, New York City.

He adds that despite the recommendations, many patients still aren't prescribed ACE inhibitors and those who are often get doses that are too small to benefit them.

"Some physicians seem to assume that lower doses of the ACE inhibitors will be as effective as high ones while reducing the risks of side effects. However, those assumptions have never been tested," Packer says. That's because most of the studies of ACE inhibitors have only tried to determine if, not how, the drugs should be used in the treatment of heart failure, he says.

Packer and his colleagues conducted a study called ATLAS (Assessment of Treatment with Lisinopril and Survival), a double-blind study comparing the usefulness and safety of high-dose and low-dose lisinopril and the risk of death and hospitalization of chronic heart failure patients.

The study involved 3,164 patients with moderate to severe congestive heart failure who were treated at 287 hospitals in 19 countries. The participants were randomly assigned to received either a low-dose ACE inhibitor (2.5 mg to 5 mg/day) or a high-dose regimen (32.5 to 35 mg/day), and they were followed for up to five years.

When compared to the low-dose group, the patients who took the higher doses of the drug had an 8 percent lower risk of death from all causes, and a 10 percent lower risk of death from heart disease.

Of more statistical significance, according to Packer, was the fact that the high-dose patients had a 12 percent lower risk of death or hospitalization for any reason compared to the low-dose group. They also had 24 percent fewer hospitalizations for congestive heart failure than the low-dose group.

Packer says the high-dose patients did experience more side effects such as dizziness, low blood pressure and worsening kidney function than the low-dose group. However, those side effects did not cause the patients in the high-dose group to quit taking the medication at a higher rate than the patients in the low-dose group.

The patients taking the high doses of the ACE inhibitors actually experienced less coughing ­ a common side effect with the drug ­ than those in the low-dose group. Packer says this means the high-dose patients had less fluid buildup in their lungs. Fluid in the lungs is a common symptom of heart failure, and is a sign that the heart is not pumping properly.

Packer says that patients with heart failure should not be treated with low doses of ACE inhibitors unless these are the only doses they can tolerate.

Co-authors are Philip A. Poole-Wilson, M.D.; Paul W. Armstrong, M.D.; John G.F. Cleland, M.D.; John D. Horowitz, M.D.; Barry M. Massie, M.D.; Lars Ryden, M.D.; Kristian Thygesen, M.D.; Barry F. Uretsky, M.D.; on behalf of the ATLAS study group.

American Heart Association

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