(Press-News.org) Patients with heart failure with reduced ejection fraction (HFrEF) did not have better health outcomes if they took sacubitril/valsartan combination therapy compared with valsartan alone, according to new data presented at the American College of Cardiology's 70th Annual Scientific Session.
Heart failure, a leading cause of hospitalization among adults over age 65, is a condition in which the heart becomes too weak to pump blood effectively to the rest of the body, causing fatigue and shortness of breath. For patients with severe heart failure, treatment options are limited to a mechanical heart pump or heart transplant. Doctors have sought ways to slow the progression of severe heart failure to delay the need for these invasive options.
The U.S. Food and Drug Administration has approved sacubitril/valsartan for treatment of heart failure, but the major clinical trial that led to the drug combination's approval, called PARADIGM-HF, had relatively few participants with New York Heart Association (NYHA) Class IV heart failure, the most severe form of the disease. The new trial, called LIFE, was designed to determine whether sacubitril/valsartan is superior to valsartan alone in patients with severe HFrEF.
The trial found no significant improvements with the combination drug when compared with valsartan in terms of the primary endpoint: change in heart failure severity as measured by the area under the curve for N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. The results also showed no difference in terms of clinical outcomes, though results for some secondary and tertiary endpoints favored valsartan, including a finding that patients taking valsartan were significantly less likely to experience hyperkalemia (elevated potassium levels).
"The results of the LIFE trial show that sacubitril/valsartan is not superior to valsartan for lowering NT-proBNP levels in patients with advanced heart failure," said Douglas L. Mann, MD, Lewin Distinguished Professor of Cardiovascular Disease at Washington University School of Medicine and the study's lead author. "This is important because the type of heart failure patients studied in the LIFE trial were sicker than the patients in PARADIGM-HF. Although the trial did not have the statistical power to evaluate endpoints such as cardiovascular death and heart failure hospitalization, when you look at the totality of the data, everything was in favor of valsartan."
For the trial, researchers enrolled 335 patients with advanced heart failure as defined by having reduced pumping capacity with an ejection fraction of less than 35% (a measure of the heart's squeezing ability for which a value of 50-70% is considered normal) as well as other physiological and functional markers of severe heart failure. Participants were randomly assigned to take either sacubitril/valsartan or valsartan alone for 24 weeks.
About one-third of patients assigned to take sacubitril/valsartan were unable to tolerate the combination drug at the full dose used in previous trials due to side effects including hypotension (low blood pressure and dizziness) and worsening renal function. These patients took a reduced dose.
"Patients with advanced heart failure are a very difficult group of patients to treat. It has been widely assumed that sacubitril/valsartan would be effective in all patients with heart failure," Mann said. "I think the drug works very effectively in patients with milder heart failure, but the results of the LIFE trial indicate that there is no evidence that sacubitril/valsartan is better than valsartan for more advanced heart failure, and there appears to be less hyperkalemia with valsartan."
The combination of sacubitril/valsartan is thought to work in part by reducing the size of the heart and improving its pumping ability.
"We make the assumption that all heart failure patients are the same and therefore will respond the same to all therapies. However, the patient population with advanced heart failure is different from patients with less advanced heart failure because of the end organ changes that occur in the heart and kidneys. These end organ changes limit the ability of the failing heart to respond to conventional therapies to the same extent as occurs in patients with milder forms of heart failure. This is one of the lessons we learned from the LIFE trial," Mann said.
The study was limited by its relatively short duration, Mann said. In addition, the sample size fell short of the planned enrollment of 400 patients since the trial was stopped early in response to the COVID-19 pandemic.
INFORMATION:
The study was funded by the National Institutes of Health with additional support from Novartis Pharmaceuticals Corporation through an investigator-initiated trial program.
Mann will be available to the media in a virtual press conference on Monday, May 17, at 9:30 a.m. ET / 13:30 UTC.
Mann will present the study, "Sacubitril/Valsartan (LCZ696) in Patients with Advanced Heart Failure and Reduced Ejection Fraction: Results of The LIFE Trial," on Monday, May 17, at 8 a.m. ET / 12:00 UTC, virtually.
ACC.21 will take place May 15-17 virtually, bringing together cardiologists and cardiovascular specialists from around the world to share the newest discoveries in treatment and prevention. Follow @ACCinTouch, @ACCMediaCenter and #ACC21 for the latest news from the meeting.
The American College of Cardiology envisions a world where innovation and knowledge optimize cardiovascular care and outcomes. As the professional home for the entire cardiovascular care team, the mission of the College and its 54,000 members is to transform cardiovascular care and to improve heart health. The ACC bestows credentials upon cardiovascular professionals who meet stringent qualifications and leads in the formation of health policy, standards and guidelines. The College also provides professional medical education, disseminates cardiovascular research through its world-renowned JACC Journals, operates national registries to measure and improve care, and offers cardiovascular accreditation to hospitals and institutions. For more, visit ACC.org.
Media Contacts
Nicole Napoli
202-669-1465
nnapoli@acc.org
Thy-Ann Nguyen
703-479-3642
thyann.nguyen@curastrategies.com
The likelihood of people surviving COVID-19 in UK hospitals has been improving over time, a new study has found.
Research published in The Lancet Respiratory Medicine by the ISARIC Coronavirus Clinical Characterisation Consortium found that in-hospital mortality declined from 32% at the start of the first wave (Mar-Apr 2020) to 16% at the end of the first wave (Jun-Jul 2020).
In their study of 63,972 adults admitted to 247 UK hospitals the researchers found reductions in mortality were observed in all age groups, in all ethnic groups, for both sexes, and in patients with and without comorbidities. This improvement was ...
A group of Brazilian and Portuguese researchers observed a correlation between the presence of lead in the organism and a microRNA (miRNA) that could be associated with the mechanisms that regulate DNA methylation, a physiological process required to control gene expression and ensure that genes function properly.
The alterations were detected in blood cells from workers in automotive battery plants, which use lead as a raw material. Curiously, lead levels in blood samples from 85 volunteers – averaging 20 micrograms per deciliter of blood (20 μg/dl) – were lower than the acceptable ceiling defined in Brazilian law (60 μg/dl).
The study was supported by FAPESP and ...
A long noncoding RNA whose function was previously unknown turns out to play an important role in promoting the body's immune response against cancer and holds promise for enhancing the efficacy of anti-cancer immunotherapy.
That's according to new findings reported in Nature Cell Biology by researchers at the University of Michigan Rogel Cancer Center.
The group dubbed the RNA they identified LIMIT -- for long noncoding RNA inducing major histocompatibility complex class I and immunogenicity of tumor.
"LIMIT is easy to remember, but really it does the opposite. It stimulates immune functions against cancer," says senior study author Weiping Zou, M.D., Ph.D., the Charles B. de Nancrede Professor of Pathology, Immunology, Biology, and Surgery at U-M.
Only a small part of the human ...
Researchers at the University of California, Davis, have found a link between traffic-related air pollution and an increased risk for age-related dementia, including Alzheimer's disease. Their study, based on rodent models, corroborates previous epidemiological evidence showing this association.
Alzheimer's disease is the most common cause of age-related dementia and the sixth leading cause of death in the United States. More than 5 million Americans currently live with Alzheimer's disease -- a number that is expected to triple by 2050 as the population ages. ...
In patients receiving therapeutic hypothermia after suffering out-of-hospital cardiac arrest, those who were cooled below 31 degrees Celsius (about 88 degrees Fahrenheit) for 24 hours showed no difference in terms of death or poor neurological outcomes at six months compared with patients receiving guideline-recommended cooling of 34 C (about 93 F). These findings are part of a study presented at the American College of Cardiology's 70th Annual Scientific Session.
Therapeutic hypothermia is a procedure in which a person's body is cooled far below normal body temperature. It has been shown to improve survival and reduce brain damage in people who have been resuscitated but remain comatose after suffering cardiac arrest (when the heart stops ...
Sperm are generally viewed as having just one action in reproduction - to fertilise the female's egg - but studies at the University of Adelaide are overturning that view.
Published in Nature Research journal Communications Biology, new research shows that sperm also deliver signals directly to the female reproductive tissues to increase the chances of conception.
Robinson Research Institute's Professor Sarah Robertson, who led the project, said: "This research is the first to show that the female immune response is persuaded by signals in sperm to allow the male partner ...
Marilyn Monroe famously sang that diamonds are a girl's best friend, but they are also very popular with quantum scientists - with two new research breakthroughs poised to accelerate the development of synthetic diamond-based quantum technology, improve scalability, and dramatically reduce manufacturing costs.
While silicon is traditionally used for computer and mobile phone hardware, diamond has unique properties that make it particularly useful as a base for emerging quantum technologies such as quantum supercomputers, secure communications and sensors.
However there are two key problems; cost, and difficulty in fabricating the single crystal diamond layer, which is smaller ...
The nanophotonics-based LiDAR technology developed by a POSTECH research team was presented as an invited paper in Nature Nanotechnology, the leading academic journal in the field of nanoscience and nanoengineering.
In this paper, a POSTECH research team (led by Professor Junsuk Rho of the departments of mechanical engineering and chemical engineering, postdoctoral researcher Dr. Inki Kim of the Department of Mechanical Engineering, and Ph.D. candidate Jaehyuck Jang of the Department of Chemical Engineering) in cooperation with the French National Science Institute (CNRS-CRHEA) focused on the LiDAR device developed through studying the metamaterials based ultralight nanophotonics.
In addition, the paper ...
Image fusion is a process that can enhance the clinical value of medical images, improving the accuracy of medical diagnoses and the quality of patient care.
Researchers at the College of Data Science Software Engineering at China's Qingdao University, have developed a new 'multi-modal' image fusion method based on supervised deep learning that enhances image clarity, reduces redundant image features and supports batch processing. Their END ...
ATS 2021, New York, NY - The COVID-19 pandemic has, and will continue to have, a tremendous impact on ICU nurses' mental health and willingness to continue in the critical care work force, according to research presented at the ATS 2021 International Conference.
Jill Guttormson, PhD, RN, associate dean for Academic Affairs and associate professor, College of Nursing, Marquette University, and colleagues sought to describe the impact of COVID-19 on ICU nurses through a survey using valid and reliable measures of burnout, moral distress, depression, anxiety, and posttraumatic stress symptoms.
The researchers recruited a national sample of nurses who have worked in the ICU during the COVID-19 pandemic between October and ...
