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New heart failure medicine touted as best advance in more than a decade

Staff Report | MUSC News Center | Sept. 3, 2014

Dr. Zile
Brennan Wesley
Dr. Michael R. Zile said results from the Paradigm-HF clinical trial will fundamentally change the current treatment of patients with chronic heart failure. 

Medical University of South Carolina (MUSC) researchers played a vital role in the landmark Paradigm-HF clinical trial, recently announced at the European Society of Cardiology congress in Barcelona, Spain (published simultaneously in the New England Journal of Medicine), which revealed Novartis’ investigational heart failure medicine (LCZ696) was superior to ACE-inhibitor enalapril in the largest heart failure study ever done.

Michael Zile, M.D., MUSC professor and Charles Ezra Daniel endowed chair for cardiology, were part of the international steering committee and helped design, implement and evaluate the study alongside numerous center principal investigators, such as MUSC cardiologist Terry O’Brien.
“I have been a cardiologist for 30 years, and this is the most important pharmaceutical clinical trial that I’ve ever been associated with or fortunate enough to participate in,” Zile said. “This will change the fundamental guidelines for therapy in heart failure patients. This medication substantially improves survival and quality of life, and proves that the care we provide is not only state-of-the-art, but also pushes the known boundaries of discovery, ultimately resulting in new, more effective ways to treat our patients.”
This new heart medication cut cardiovascular deaths by 20 percent for patients with heart failure with reduced ejection fractions (HF-REF) versus ACE-inhibitor in the landmark Paradigm-HF trial. Patients who were given LCZ696 were more likely to be alive and less likely to have been hospitalized for sudden deterioration of their heart failure than those given ACE-inhibitor enalapril. Patients received LCZ696 or enalapril in addition to the current standard of care. More than 5 million people suffer from heart failure in the United States, facing a high risk of death and poor quality of life despite currently available medicines.

In the study, the benefit of LCZ696 was seen early, resulting in an early closure of the study from the National Institutes of Health. LCZ696 reduced the risk of death from cardiovascular causes by 20 percent; reduced heart failure hospitalizations by 21 percent; and reduced the risk of all-cause mortality by 16 percent.
LCZ696 reduces the strain on the failing heart by enhancing protective systems of the heart while simultaneously suppressing the harmful effects of overactive systems in these patients’ hearts. Despite existing therapies, the mortality rate remains very high with up to 50 percent of patients dying within five years of a diagnosis of heart failure. Approximately half of patients with heart failure have HF-REF. Analysis of the safety data from Paradigm-HF showed side effects were manageable in the study, and included elevated serum potassium levels, symptomatic hypotension and cough.

Novartis plans to file a new drug application with the FDA by the end of 2014.

Given the significant results of the Paradigm trial, Novartis is opening a second five-year study called the Paragon-HF trial that will test the same drug in patients with heart failure with preserved ejection fraction (HFpEF).  Heart failure patients can be divided into two groups - heart failure with a reduced ejection fraction, which used to be called systolic heart failure and heart failure with a preserved ejection fraction, HF-PEF, which used to be called diastolic heart failure.  Ejection fraction is a measure of the forward pumping ability of the heart, the fraction of blood ejected from the heart with each heart beat.

According to Zile, more than half of these patients will not survive beyond five years, and 50 percent of those hospitalized are likely to be readmitted within six months. Like HFrEF, patients with preserved ejection fraction endure a difficult quality of life and a reduced ability to participate in everyday activities. “HFpEF is very common, very lethal, and it causes an unbelievable burden on our patients. To date, zero clinical trials have demonstrated that you can improve morbidity and mortality for them,” Zile said.

Zile said Novartis has just begun the largest trail in patients with HFpEF ever performed and MUSC will be enrolling participants soon. For more information or to learn about enrollment in the PARAGON trial, call 843-792-3738.

To view multimedia information associated with this release from Novartis, visit this website.



Related Stories >>

New Novartis drug effective in treating heart failure (The New York Times)

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