Breaking News
March 24, 2019 - Practices for Reducing COPD Hospital Readmissions Explored
March 24, 2019 - Could an eye doctor diagnose Alzheimer’s before you have symptoms?
March 24, 2019 - Enzyme inhibitor stops inflammation and neurodevelopmental disorders in mouse models
March 24, 2019 - Walk, Dance, Clean: Even a Little Activity Helps You Live Longer
March 24, 2019 - Americans used less eye care in 2014 versus 2008
March 24, 2019 - Study finds link between depression in 20s linked to memory loss in 50s
March 24, 2019 - New tool helps physiotherapy students to master complex fine motor skills
March 24, 2019 - The AMR Centre secures £2.3m funding boost
March 24, 2019 - Study examines effects of taking ondansetron during first trimester of pregnancy
March 24, 2019 - Researchers identify a more effective treatment for cancer
March 24, 2019 - Open-source solution for multiparametric optical mapping of the heart’s electrical activity
March 24, 2019 - New nanotechnology approach shows promise in treating triple negative breast cancer
March 24, 2019 - Trevena Announces Publication of APOLLO-1 Results in The Journal of Pain Research Highlighting Oliceridine’s Potential for Management of Moderate-to-Severe Acute Pain
March 24, 2019 - Maternal deaths following C-section 50 times higher in Africa compared to high-income countries
March 24, 2019 - Apple watch could detect irregular heart beat says study
March 24, 2019 - Queen Mary University of London’s BCI boosts radionuclide imaging capabilities with MILabs VECTor technology
March 24, 2019 - Girls should be encouraged to gain more ball skills, shows study
March 24, 2019 - Acute doses of synthetic cannabinoid can impair critical thinking and memory
March 24, 2019 - Presence of bacteria in urine does not always point to infection, shows study
March 24, 2019 - Scientists identify a new role for nerve-supporting cells
March 24, 2019 - Hidden differences between pathology of CTE and Alzheimer’s disease discovered
March 24, 2019 - Knowing causative genes of osteoporosis may open door to more effective treatments
March 24, 2019 - Toilet-seat based cardiovascular monitoring system getting ready to begin commercialization
March 24, 2019 - New model for intensive care identifies factors that send ill patients to ICU
March 24, 2019 - Recommendations Issued for HSCT in Multiple Myeloma
March 24, 2019 - Deep brain stimulation provides sustained relief for severe depression
March 24, 2019 - “Statistical significance” may soon be a thing of past?
March 24, 2019 - Researchers track effects of epigenetic marks carried by sperm chromosomes
March 24, 2019 - AHA News: Family Adopts Three Children With Three Different Heart Conditions
March 24, 2019 - Research into opioid painkillers could provide clues for safer drug development
March 23, 2019 - Lung cancer survivor recounts her lifetime struggles
March 23, 2019 - Radial and femoral approach for PCI achieve similar results in terms of survival
March 23, 2019 - Study sheds light on the optimal timing of coronary angiography in NSTEMI patients
March 23, 2019 - Excess hormones could cause a condition that can lead to blindness in women, study finds
March 23, 2019 - Dramatic shifts in first-time opioid prescriptions bring hope, concern
March 23, 2019 - Antidepressant drugs may not work when neurons are out of shape
March 23, 2019 - TTUHSC El Paso to establish endowed chair in neurology through a major grant
March 23, 2019 - New device approved by FDA for treating patients with moderate-to-severe heart failure
March 23, 2019 - People with peripheral artery disease have lower Omega-3 Index, shows research
March 23, 2019 - Trigger warnings have minimal impact on how people respond to content, shows research
March 23, 2019 - Gilead Announces Data From Two Studies Supporting Further Development of GS-6207, a Novel, Investigational HIV-1 Capsid Inhibitor as a Component of Future Long-Acting HIV Therapies
March 23, 2019 - Selfish genetic elements amplify inflammation and age-related diseases
March 23, 2019 - Study provides new understanding of how the brain recovers from damage caused by stroke
March 23, 2019 - CRISPR/Cas libraries could revolutionize drug discovery
March 23, 2019 - Allergic reaction during pregnancy may alter sexual-development in offspring’s brain
March 23, 2019 - Seeing through a robot’s eyes helps those with profound motor impairments
March 23, 2019 - Recent research shows that ease of breastfeeding after C-section differs culturally
March 23, 2019 - Newly discovered parameters offer more control over efficient release of drugs
March 23, 2019 - ‘De-tabooing’ of abortion- Women would like more support from health care community
March 23, 2019 - Anti-TB drugs can increase susceptibility to Mtb reinfection
March 23, 2019 - New survey indicates need of attention to neglected tropical diseases
March 23, 2019 - Innovative in vitro method to develop easy-to-swallow medicine for children and older people
March 23, 2019 - Sugary drinks could raise risk of early deaths finds study
March 23, 2019 - Lian wins ENGINE grant for stem-cell-based therapy to treat Type 1 diabetes
March 23, 2019 - Overall, Physicians Are Happy and Enjoy Their Lives
March 23, 2019 - Researchers discover how blood vessels protect the brain during inflammation
March 23, 2019 - CDC study shows modest improvement in optimal hospital breastfeeding policy
March 23, 2019 - Family-based prevention program to reduce alcohol use among older teens
March 23, 2019 - Remote monitoring of implanted defibrillators in heart failure patients prevents hospitalizations
March 23, 2019 - Appropriate doffing of personal protective equipment may reduce healthcare worker contamination
March 23, 2019 - Window screens can suppress mosquito populations, reduce malaria in Tanzania
March 23, 2019 - Researchers discover new biomarker for postoperative liver dysfunction
March 23, 2019 - Pregnancy history may be linked to cognitive function in older women, finds study
March 23, 2019 - Study shows ticagrelor is equally safe and effective as clopidogrel after heart attack
March 23, 2019 - FDA Approves First Drug for Postpartum Depression, Zulresso (brexanolone)
March 23, 2019 - New guidelines outline new treatment management for psoriasis
March 23, 2019 - Thermally abused cooking oil may promote progression of breast cancer
March 23, 2019 - High-fructose corn syrup fuels growth of colon tumors in mice
March 23, 2019 - Partnership aims at establishing best practices to promote diversity in clinical trials
March 23, 2019 - New study examines presence of microbes in tap water from residences, office buildings
March 23, 2019 - Early life trauma may affect brain structure, contribute to major depressive disorder
March 23, 2019 - NIH starts clinical trial of drug to treat cravings associated with opioid use disorder
March 23, 2019 - Cervix bacteria, immune factors could be a warning signal of premature birth, reports new research
March 23, 2019 - Worst-ever emergency care performance figures underscore the need to focus on staffing
March 23, 2019 - The Current issue of “The view from here” is concerned with Cancer
March 23, 2019 - Mouse model validates how ‘good’ and ‘bad’ bacteria affect acne
March 23, 2019 - Individual amygdala neurons respond to touch, imagery and sounds
March 23, 2019 - Combination of two topical creams can prevent cancer
March 23, 2019 - Study suggests depression screening when assessing African-Americans for schizophrenia
March 23, 2019 - New electronic support system for choosing drug treatment based on patient’s genotype
Inhaled therapy for heart failure fails to meet either primary or secondary endpoints

Inhaled therapy for heart failure fails to meet either primary or secondary endpoints

image_pdfDownload PDFimage_print

Four weeks of treatment with a novel inhaled medication failed to improve exercise capacity, daily activity levels, severity of symptoms or quality of life in patients with a type of heart failure for which no effective treatment options currently exist, according to research presented at the American College of Cardiology’s 67th Annual Scientific Session.

The first multicenter trial of an inhaled therapy for heart failure fell short of meeting either its primary or secondary endpoints, said Barry A. Borlaug, MD, professor of medicine at Mayo Clinic in Rochester, Minnesota, and principal investigator for the study.

The trial involved patients who have heart failure with preserved ejection fraction (HFpEF). Of the approximately 6 million Americans with heart failure, roughly half have HFpEF. As the population ages, the number of people with this type of heart failure is expected to increase. To date, no treatment has conclusively shown to improve outcomes in patients with HFpEF, Borlaug said.

“We are disappointed that this treatment strategy failed to live up to the promise it had shown in preliminary studies,” Borlaug said. “We need to redouble our efforts to find an effective approach to treating this patient population, which represents a huge unmet public health need.”

Ejection fraction is a measure of how much blood the heart can pump out each time it contracts. With a normal ejection fraction, 50 percent to 70 percent of the blood in the heart is pumped out with each heartbeat. In heart failure with reduced ejection fraction—the better known, and more treatable, form of the disease—weakness of the heart muscle means that only 40 percent or less of the blood in the heart is pumped out with each heartbeat. In HFpEF, by contrast, the ejection fraction is normal. But because the heart muscle is abnormally stiff the heart has difficulty filling with an adequate amount of blood.  

“With a stiff heart, the effort involved in filling it with blood leads to high pressure, which backs up into the lungs, causing lung pressure to increase and creating a feeling of shortness of breath,” Borlaug said.

Nitric oxide, a gas produced by cells that line the body’s arteries, plays a key role in relaxing blood vessels and decreasing heart muscle stiffness. Previous research suggested that increasing nitric oxide activity in the body might help to improve shortness of breath in patients with HFpEF. However, prior studies have not identified an effective way of delivering the nitric oxide to the bloodstream.

The current study tested inorganic nitrite, a byproduct of the breakdown of nitric oxide in the body that can be converted back into nitric oxide during physical activity. Preliminary studies suggested that inhalation of inorganic nitrite could reduce pressure in the heart and improve exercise capacity.

The trial enrolled 105 patients who had HFpEF causing shortness of breath and fatigue with ordinary or mild physical activity. Their median age was 68 years; 57 percent were women, 81 percent had high blood pressure and 31 percent had diabetes. Patients were randomly assigned to receive either the medication or a placebo, administered with a nebulizer three times a day for four weeks. All patients were trained in how to use the nebulizer to inhale the medication.

After four weeks, the two groups switched, so that by the end of the study all patients had received both the study medication and the placebo. The study was double-blinded, meaning that neither patients nor their doctors knew who was receiving which treatment.

The primary endpoint was change in maximal exercise capacity, or the maximum amount of oxygen that the body can consume, which is an indicator of cardiac output, Borlaug said. Secondary endpoints included changes in patients’ daily activity levels, measured by portable accelerometers that they wore; quality of life; and severity of heart failure symptoms.  

After analyzing patient data collected at the end of the study, researchers found no significant differences for any of the primary or secondary endpoints. At baseline, exercise capacity (peak oxygen consumption) was severely depressed (13.5 mL/kg/min). In the group receiving nitrite, there was no effect on peak VO2 as compared with the placebo group. Similarly, there was no significant between-group differences in daily activity levels, health-related quality of life scores, symptom severity classification, echocardiographic and exercise measures, or NT-proBNP levels, which reflect the degree of stress on the heart. There were no differences in serious adverse events.

There are several factors that may have influenced the trial outcomes, Borlaug said. First, patients needed to use the nebulizer three times a day for about 10 minutes each time.

“It’s arduous to take any medication three times a day,” he said. “Needing to set aside time three times every day to do a 10-minute treatment could have interfered with adherence.”

The research team will be analyzing study data on adherence, he said.

Second, four weeks of treatment may not have provided sufficient exposure to the medication to improve exercise capacity or quality of life, and the duration of time where the medicine remains active in the blood stream may not have been long enough.

Third, the study did not require patients to increase their activity levels as part of its design. Prior studies have suggested that exercise training can improve exercise capacity and quality of life in people with HFpEF, he said.

“The medication may be like the gas that can make the car go, but without a spark to ignite it, the car doesn’t move,” he said.

Borlaug said he is currently conducting another study that is looking at whether patients with HFpEF who get both exercise training and the nitrite medication do better than similar patients who get exercise training and a placebo.

The current study was conducted in the Heart Failure Network, which is funded by a grant from the National Heart, Lung, and Blood Institute. Aires Pharmaceuticals Inc. provided additional funding, as well as the device and investigational drug.

Source:

http://www.acc.org/about-acc/press-releases/2018/03/10/10/39/sun-1045am-inhaled-therapy-ineffective-in-difficult-to-treat-heart-failure

Tagged with:

About author

Related Articles