Study: Larger dose of ARBs is more effective in heart failure patients

American Heart AssociationNov 18 2009

Study highlights:

-- A study of nearly 4,000 heart failure patients finds that a larger dose of angiotensin receptor blockers (ARBs) works better than a smaller dose.

-- The higher dose was associated with a 10.1 percent relative risk reduction (in the combined primary end-point of all-cause mortality and hospitalization for heart failure) versus the lower dose, mostly due to a reduction in the risk of heart failure hospitalizations.

-- There was no significant difference in all-cause mortality between groups.

A larger dose of angiotensin receptor blockers (ARBs) is more effective than a smaller dose in heart failure patients, researchers said at the American Heart Association's Scientific Sessions 2009.

The Comparison of Low-Dose vs. High-Dose Losartan Treatment on Morbidity and Mortality in Angiotensin-Converting Enzyme Inhibitor-Intolerant Patients with Heart Failure and Reduced Left Ventricular Ejection Fraction: Results of the HEAAL Study is the first to examine the relative impact of different ARB doses on clinical outcomes.

"In fact, HEAAL represents one of very few dose-related comparative outcome studies ever conducted with any cardiovascular drug," said Marvin A. Konstam, M.D., principal investigator of the study, Professor of Medicine at Tufts University School of Medicine and Director of Tufts Medical Center's Cardiovascular Center, in Boston, Mass. "We were able to document that the higher of the two losartan doses we compared was needed to achieve the optimal benefit on both outcomes and symptoms."

The investigators followed 3,834 heart failure patients in 30 countries who were randomized to receive either 50 milligrams (mg) or 150 milligrams a day of the ARB losartan between November 2001 and March 2005. All of the patients had heart failure (HF), a reduced heart pumping ability determined by their left ventricular ejection fraction, and all were receiving an ARB because of intolerance to another common and related class of heart failure drugs called angiotensin-converting enzyme inhibitors (ACEi).

During a median follow-up of 4.7 years, 1,717 primary endpoint events (a composite of all-cause death or hospitalization for HF) occurred: 828 in the high-dose group vs. 889 in the low-dose group. That means the higher dose was associated with a 10 percent risk reduction vs. the lower dose, mostly due to a 13 percent reduction in the risk of heart failure hospitalizations.

The researchers found no significant difference in all-cause mortality between groups.