Vasodilators first choice for some heart patients

(2005-07-10)

Few front-line medications exist for treating hospitalized patients with acute decompensated heart failure, a stage of heart failure marked by heightened severity and often-lengthy hospital stays with frequent readmissions. Now, a study suggests the list of preferred drugs for treating the disease might be even shorter.

In a study released today (7/5) in the Journal of the American College of Cardiology, researchers found that two particular drugs were associated with substantially lower in-hospital mortality than two other drugs that also are commonly used for treating patients with acute decompensated heart failure (ADHF).

The retrospective study draws from a multi-institutional registry of 65,180 patients with ADHF. In comparisons of patients treated intravenously with nitroglycerin, nesiritide, dobutamine or milrinone, there was a lower in-hospital mortality rate for patients administered nitroglycerin or nesiritide than the drugs dobutamine or milrinone.

According to Dr. William T. Abraham, lead author of the study and director of cardiovascular medicine at the Richard M. Ross Heart Hospital at The Ohio State University, the findings may surprise some in the medical community, particularly those who favor the use of positive inotropes, the group of drugs that includes dobutamine and milrinone.

"This is a significant finding from a large population of patients and will certainly aid in the development of guidelines for treating patients with acute decompensated heart failure," said Abraham.

Congestive heart failure is characterized by a progressive loss in the heart's ability to pump blood. When a patient's condition suddenly or rapidly deteriorates to the point that hospitalization is required, the patient is described as having experienced acute heart failure or acute decompensated heart failure.

Positive inotropes increase the pumping action of the heart, while nitroglycerin and nesiritide act as vasodilators, causing the blood vessels to dilate and reducing the amount of effort needed by the heart to pump blood to the body.

For the study, 15,230 patients in the registry received one or more of the four drugs. Nitroglycerin was given to 6,549 patients, nesiritide, 5,220; milrinone, 2,021; and dobutamine, 4,226. The therapies administered were based on clinician judgment, not on a randomized protocol. Another 49,950 patients in the registry did not receive any of the four drugs, presumably because their heart failure was less severely worsened.

After adjusting for differences in patient characteristics, mortality was similar for patients given nitroglycerin or nesiritide, while patients given milrinone or dobutamine experienced an approximately 35 percent to 50 percent increase in the chance of dying in the hospital. Between the latter two agents, dobutamine was associated with higher in-hospital mortality than milrinone.

"Our study suggests that inotropes be reserved for patients who fail with vasodilators or are so severely ill that vasodilators alone are likely to be inadequate treatment," said Abraham, also associate director for clinical/translational research at Ohio State's Davis Heart and Lung Research Institute.

Abraham stresses that nitroglycerin and nesiritide appear to be equally safe in the treatment of ADHF and that other criteria should be considered when choosing between the two drugs.

People with this life-threatening degree of heart failure are usually treated in a hospital setting due to the severity of their illness and the intensity of their treatment. While guidelines exist for treating outpatients with chronic heart failure, a lack of statistical data has prevented similar guidelines from being established for ADHF.

Creation in 2001 of the Acute Decompensated Heart Failure National Registry (ADHERE) has helped coordinate and expedite the collection of data from more than 275 hospitals from across the country. The registry is the first of its kind to gather detailed information about patients with ADHF. Patients with a primary diagnosis of heart failure admitted to any of the participating hospitals are entered in the registry. Data for the study was taken from patients treated from late 2001 to mid-2003.

Acute heart failure is the leading cause of hospitalization in persons over age 65 years of age and accounts for approximately 1 million hospital admissions each year in the United States.

This study was funded by Scios Inc. The biopharmaceutical company was acquired by Johnson & Johnson in 2003. Abraham is a consultant for Scios Inc.

David Crawford
crawford.1@osu.edu
614-293-3737
Ohio State University Medical Center
http://www.osumedcenter.edu