BOCA RATON, FLA. — A ?-blocker can reverse cardiac remodeling and increase left ventricular ejection fraction in asymptomatic heart failure patients, according to a double-blind, randomized, placebo-controlled study presented at the annual meeting of the Heart Failure Society of America.
Metoprolol succinate extended-release tablets (Toprol-XL, AstraZeneca) are indicated for treatment of New York Heart Association class II and III patients with heart failure of ischemic, hypertensive, or cardiomyopathic origin. In symptomatic patients with heart failure and left ventricular systolic dysfunction, Toprol-XL reduced left ventricular volumes after 6 months of treatment in previous research, said Wilson S. Colucci, M.D.
To determine whether the once-daily agent provides a similar benefit in asymptomatic patients, Dr. Colucci and his colleagues randomized 164 NYHA class I patients at 44 U.S. sites to receive a 50-mg or 200-mg dose of metoprolol extended-release tablet daily or placebo.
All the participants in the Reversal of Ventricular Remodeling with Toprol-XL (REVERT) study had a baseline left ventricular ejection fraction (LVEF) below 40%. All also had evidence of cardiac remodeling at baseline, defined as a left ventricular end-diastolic volume index greater than 75 mL/m2. Mean age was 66 years, 25% were women, and 54% had heart failure of an ischemic etiology.
“In heart failure there are progressive enlargement and structural changes to the heart known as remodeling, which is initially compensatory but ultimately maladaptive,” said Dr. Colucci, section chief of cardiovascular medicine at Boston University.
Left ventricular end-systolic volume index was measured echocardiographically after 1 year. This index decreased by 15 mL/m2 with the 200-mg dose of metoprolol, by 8 mL/m2 with the 50-mg dose, and by 4 mL/m2 with placebo. During the same year, LVEF increased 6% with the 200-mg dose, 4% with the 50-mg dose, and 0% with placebo.
“The REVERT study results show a reduction in this measure of left ventricular volume in asymptomatic heart failure patients with left ventricular systolic dysfunction,” and they provide scientific data on cardiac remodeling in such patients, Dr. Colucci said.
The participants received metoprolol or placebo in addition to their existing medications. For example, at study entry, 92% were taking an ACE inhibitor or angiotension receptor blocker, and 65% were taking a diuretic. There were “very minimal changes” in medications during the study, and no participant used a cardiac resynchronization therapy device, he said.
When asked by an attendee about heart rate changes in the study, Dr. Colucci said, “There was a very strong relationship between dose and heart rate decrease. … We have not looked at whether anything in the demographics predicted that change.”
The REVERT study was sponsored by AstraZeneca. Dr. Colucci has no conflict of interest disclosure regarding the agent studied or AstraZeneca.