American Heart Association Late Breaking Clinical Trial Report: High Dose Of Angiotensin Receptor Blockers Effective In Heart Failure Patients

Main Category: Heart Disease
Also Included In: Cardiovascular / Cardiology;  Clinical Trials / Drug Trials
Article Date: 18 Nov 2009 - 3:00 PDT

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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.

Study Sponsors are: Merck Inc., manufacturer of losartan. The trial's decision-making was driven by the academic Steering Committee with all analyses performed or confirmed by an independent academic statistician.

Co-authors are: James D. Neaton, Ph.D.; Kenneth Dickstein, M.D.; Helmut Drexler, M.D. (deceased); Michel Komajda, M.D.; Felipe A. Martinez, M.D.; Gunter A.J. Riegger, M.D.; Ronald D. Smith, Ph.D.; William Malbecq, Ph.D.; Soneil Guptha, M.D.; and Philip A. Poole-Wilson, M.D. (deceased). The HEAAL research group dedicated the presentation to the memories of Drs. Drexler and Poole-Wilson.

Disclosures: Drs. Konstam, Neaton, Dickstein, Drexler, Komajda, Martinez, Riegger and Poole-Wilson are or were consultants to Merck. Dr. Malbecq is an employee of Merck. Dr. Smith was previously an employee of Merck and is presently a consultant to Merck. Dr. Guptha was previously an employee of Merck.

Statements and conclusions of study authors published in American Heart Association scientific meetings are solely those of the study authors and do not necessarily reflect the association's policy or position. The association makes no representation or guarantee as to their accuracy or reliability. The association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific association programs and events.

Source: American Heart Association

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