August 31, 2017, Cleveland: A team of Cleveland Clinic researchers found that a common heart disease medication, beta blockers, may help treat pulmonary arterial hypertension (PAH), a debilitating lung disease.
Caused by high blood pressure in the pulmonary arteries, PAH is a progressive disease which usually leads to right-sided heart failure and death within five to seven years of diagnosis. In fact, right-sided heart failure is the leading cause of death in PAH patients.
Right ventricular dysfunction (which leads to right-sided heart failure) occurs independently of increased blood pressure, yet all currently approved PAH treatments target the pulmonary vessels, rather than address the heart dysfunction that is the more likely cause of death in these patients.
In contrast, targeting left ventricular dysfunction has been the foundation of left-sided heart failure therapy for nearly 40 years. Specifically, beta-adrenergic receptor blockade ("beta blockers") have been a cornerstone therapy for improving left ventricular function.
"There is a critical need for new therapies to support right ventricular function in pulmonary hypertension," said lead author Serpil C. Erzurum, M.D., Chair of Cleveland Clinic Lerner Research Institute. "While treatments with beta blockers such as carvedilol are standard therapy in patients with left-sided heart failure, successful therapies in right-sided heart failure and PAH have lagged behind. Longer-term studies are needed but our initial analysis shows that carvedilol may also benefit patients with PAH, who currently have few available treatment options."
The Cleveland Clinic team assessed carvedilol use in a group of 30 patients with PAH in a double-blind, randomized study. The participants received either placebo, low fixed-dose, or escalating doses of carvedilol over a six-month period. They found that the drug lowered heart rate in correlation with carvedilol dose, improved heart rate recovery from exercise, and did not worsen heart failure or lead to airflow deterioration. The findings suggest carvedilol is safe to use in PAH patients for six months with evidence of improved outcomes that could prevent right-sided heart failure.
Previously, the use of beta blockers in PAH patients has not been widely studied due to mostly anecdotal concerns about decreased functional lung capacity.
"There is good reason to consider beta blockers for the right ventricular failure in PAH," said W. H. Wilson Tang, M.D., study co-author and advanced heart failure/transplant cardiologist at Cleveland Clinic. "The fact that beta blockers were well-tolerated and effective in lowering heart rates thereby improving the heart efficiency is unto itself a key observation, since doctors have been cautioned against using them in this setting for safety concerns. This study provides important new data that advances our knowledge of using this class of drugs in this chronic and life-threatening lung-associated vascular disease."
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Dr. Erzurum holds the Alfred Lerner Memorial Chair in Innovative Biomedical Research and is a member of the medical staff in Lerner Research Institute's Department of Pathobiology and Cleveland Clinic's Respiratory Institute.
Samar Fahra, M.D., is first author on the study, which was published in JCI Insight. This work was supported by National Institutes of Health (NIH) grants R01HL115008 and R01HL60917 and in part by the National Center for Advancing Translational Sciences, UL1TR000439.
About Cleveland Clinic
Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. U.S. News & World Report consistently names Cleveland Clinic as one of the nation's best hospitals in its annual "America's Best Hospitals" survey. Among Cleveland Clinic's 51,000 employees are more than 3,500 full-time salaried physicians and researchers and 14,000 nurses, representing 140 medical specialties and subspecialties. Cleveland Clinic's health system includes a 165-acre main campus near downtown Cleveland, 10 regional hospitals, more than 150 northern Ohio outpatient locations - including 18 full-service family health centers and three health and wellness centers - and locations in Weston, Fla.; Las Vegas, Nev.; Toronto, Canada; Abu Dhabi, UAE; and London, England. In 2016, there were 7.1 million outpatient visits, 161,674 hospital admissions and 207,610 surgical cases throughout Cleveland Clinic's health system. Patients came for treatment from every state and 180 countries. Visit us at clevelandclinic.org. Follow us at twitter.com/ClevelandClinic.
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About the Lerner Research Institute
The Lerner Research Institute is home to Cleveland Clinic's laboratory, translational and clinical research. Its mission is to promote human health by investigating in the laboratory and the clinic the causes of disease and discovering novel approaches to prevention and treatments; to train the next generation of biomedical researchers; and to foster productive collaborations with those providing clinical care. Lerner researchers publish more than 1,500 articles in peer-reviewed biomedical journals each year. Lerner's total annual research expenditure was $260 million in 2016 (with $140 million in competitive federal funding, placing Lerner in the top five research institutes in the nation in federal grant funding). Approximately 1,500 people (including approximately 200 principal investigators, 240 research fellows, and about 150 graduate students) in 12 departments work in research programs focusing on heart and vascular, cancer, brain, eye, metabolic, musculoskeletal, inflammatory and fibrotic diseases. The Lerner has more than 700,000 square feet of lab, office and scientific core services space. Lerner faculty oversee the curriculum and teach students enrolled in the Cleveland Clinic Lerner College of Medicine (CCLCM) of Case Western Reserve University - training the next generation of physician-scientists. Institute faculty also participate in multiple doctoral programs, including the Molecular Medicine PhD Program, which integrates traditional graduate training with an emphasis on human diseases. The Lerner is a significant source of commercial property, generating 64 invention disclosures, 15 licenses, 121 patents, and one new spinoff company in 2016. Visit us at http://www.lerner.ccf.org. Follow us on Twitter at http://www.twitter.com/CCLRI.
Journal
JCI Insight