Drug produces cascade of positive outcomes in acute heart failure
ORLANDO, Fla.—In acute heart failure patients, the use of relaxin, a naturally occurring hormone, was found to improve the hospital course of patients, prevent heart failure from worsening during hospitalization and shortened hospital stay, according to research presented Sunday during a late-breaking clinical trials session at the American College of Cardiology (ACC) 58th Annual Scientific Session.

“The use of relaxin led to considerable improvement in dyspnea when compared to placebo and lasted up to 14 days, longer than any therapy studied,” said co-principal investigator John R. Teerlink, MD, a professor of clinical medicine at the University of California San Francisco and director of the Heart Failure Clinic at the San Francisco Veterans Affairs Medical Center.  

Relaxin, which causes blood vessels to dilate, takes pressure off the heart, and increases blood flow to the kidneys, has the potential to improve ventricle performance in acute heart failure patients. These effects may be particularly beneficial in the approximately 60 percent to 80 percent of patients who initially have normal or high blood pressure, since constriction of blood vessels likely plays a central role in their acute heart failure, Teerlink reported. 

“There has been a focus on chronic heart failure patients over the years without a concomitant focus on acute heart failure patients,” Teerlink told Cardiovascular Business News. “Acute heart failure accounts for 1 million primary hospitalizations each year and more than 3 million contributing hospitalizations. It is the leading cause of hospitalization in patients over the age of 65—and this number will continue to grow as the population ages. While we have progressively decreased mortality and morbidity associated with chronic heart failure in the last 15 years, the in-hospital mortality and the rehospitalizations associated with acute heart failure have not changed significantly.” 

The great majority of acute heart failure patients have congested lungs that cause shortness of breath and other complications. For these patients, the current standard of care includes diuretics and vasodilators. Available agents from both of these classes of agents have been associated with renal impairment, hypotension and adverse outcomes, according to Teerlink. 

The Pre-RELAX-AHF randomized, double-blind, placebo-controlled international study was designed to evaluate the safety and best dose of intravenous relaxin (Corthera) in patients with acute heart failure and normal or elevated blood pressure. Researchers evaluated 234 patients and found that the 30-mcg/kg dose (relaxin-30) was the most effective. 

More patients (41 percent) reported moderate or marked improvements in dyspnea at six, 12 and 24 hours when treated with relaxin-30, as compared to 23 percent of patients assigned to placebo. Relief remained significantly greater in the relaxin-30 group at day 14, Teerlink said.  

Researchers also noted trends toward greater fluid and weight loss, less need for intravenous diuretics, and less deterioration of heart failure in the hospital. When all of the doses of relaxin were compared with placebo, hospital stay was one to two days shorter, on average, Teerlink said.  

“How could a drug given for 24 to 48 hours improve long-term outcomes? We know that patients with bad hearts do better on chronic ACE inhibitors and beta-blocker therapy. Patients on relaxin improved to the point that their physicians felt comfortable putting them on these other therapies, which contributed to better long-term outcomes,” Teerlink said.  

“We have this drug that reduces congestion, helps the kidneys deal with the extra volume load without decreasing kidney function, improves urine output with less diuretics, decreases body weight, decreases worsening heart failure events, and improves outcomes by getting people onto better therapies. We’re seeing a cascade of positive outcomes from this drug,” he said.  

After 60 days, 17 percent of patients in the placebo group either died from or were readmitted for cardiovascular causes, compared to no deaths and 3 percent of patients in the relaxin group who had to be readmitted for cardiovascular causes--more than an 80 percent reduction in the relaxin arm.

During an average follow-up of 4.5 months, no patients in the relaxin-30 group died of cardiovascular causes, as compared with 14 percent of those in the placebo group. 

"The results of the study clearly indicate favorable treatment effects on symptoms, signs and outcomes in patients hospitalized with acute heart failure," Teerlink concluded.

Corthera sponsored the study. Teerlink has received consulting fees and grants from Corthera. The study was simultaneously published online in The Lancet.