Tezosentan didn't change outcomes for patients with sudden, life-threatening attacks, trial shows
TUESDAY, Nov. 6 (HealthDay News) -- An experimental kind of medication has failed as treatment for the emergency condition known as acute heart failure, a new trial finds.
The drug, tezosentan, did not improve patients' breathlessness, reduce their incidence of major cardiovascular events, or cut their risk of death after acute heart failure, concludes an international study published in the Nov. 7 issue of the Journal of the American Medical Association.
"This is an investigational new drug that is an endothelin receptor blocker," explained study co-author Dr. John R. Teerlink, an associate professor of medicine at the University of California, San Francisco.
Endothelin is "one of the most potent vasoconstrictors known," Teerlink said, meaning that it causes blood vessels to become narrower. In fact, it has similar properties to snake venom, he said.
Episodes of acute heart failure can occur in people with chronic heart failure, in which the heart slowly loses the ability to pump blood. The loss of that ability occurs suddenly in an acute episode, leaving a person gasping for breath. The lungs can fill rapidly with fluid, and the episode can be fatal.
While chronic heart failure is routinely managed with a variety of drugs, including beta blockers and fluid-reducing diuretics, "all the available agents for acute heart failure have significant side effects," Teerlink said.
Many existing medications, such as nitroglycerin, act by causing blood vessels to become wider, improving blood low. Tezosentan would act differently, by preventing blood vessels from narrowing.
In the study, more than 1,400 people who suffered episodes of acute heart failure were either given infusions of tezosentan for up to 72 hours or a placebo.
The drug did not improve breathlessness more than placebo, the researchers found. The incidence of death or worsening heart failure after seven days was 26 percent for patients in each group, and the six-month death rate was 14.3 percent for both groups.
The drug's failure to improve outcomes is a major disappointment, said Dr. Randall Starling, director of heart failure and transplantation at the Cleveland Clinic.
"The treatment of acute heart failure is clearly an area with an unmet need," Starling said. "The majority of patients with shortness of breath and congestion are treated with intravenous diuretics. There is a 10 to 12 percent death rate and a 20 percent readmission rate within 30 days. There is also serious concern among physicians that the treatment may have deleterious effect on kidney function."
But several promising drugs now are in large-scale trials, said Dr. Christopher M. O'Connor, professor of medicine and director of the heart center at Duke University in Durham, N.C. Results of one trial, which has enrolled 7,500 patients, are expected in about a year, while a second trial of another agent may become available in two to three years, he said.
And the last word on tezosentan may not yet have been spoken, Teerlink added.
"This study does not preclude potential studies in the future to assess its effectiveness in a more defined patient population," he said.
There's more on heart failure at the U.S. National Library of Medicine.
SOURCES: John R. Teerlink, M.D., associate professor, medicine, Universiy of California, San Francisco; Randall Starling, M.D., director, heart failure and tranplantation, Cleveland Clinic; Christopher M. O'Connor, M.D., professor, medicine, Duke University, Durham, N.C.; Nov. 7, 2007, Journal of the American Medical Association
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