Beta Blockers Have Positive Effect in Pulmonary Arterial Hypertension

Cleveland Clinic team addresses critical need

A team of Cleveland Clinic researchers has determined that beta blockers may help treat pulmonary arterial hypertension (PAH).

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Right-sided heart failure is the leading cause of death in PAH patients. Right ventricular dysfunction occurs independently of increased blood pressure, yet all currently approved PAH treatments target the pulmonary vessels rather than address 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; beta blockers are the cornerstone therapy in left-sided heart failure.

“There is a critical need for new therapies to support right ventricular function in pulmonary hypertension,” said lead author Serpil Erzurum, MD, practicing pulmonologist and 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.”

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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. Results showed 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.

Decreased functional lung capacity a myth

Previously, the use of beta blockers in PAH patients had not been widely studied due mostly to 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, MD, study co-author and staff cardiologist in the Section of Heart Failure and Cardiac Transplantation Medicine in the Sydell and Arnold Miller Family Heart & Vascular Institute 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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Samar Fahra, MD, associate staff in the Respiratory Institute, 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.