Carvedilol shows benefits for PAH without airway deterioration

Beta blockers may offer a new avenue of therapy for pulmonary arterial hypertension (PAH), according to findings from researchers at the Cleveland Clinic. The study was published in JCI Insight.

PAH is a progressive, debilitating lung disease that is caused by elevated blood pressure in the pulmonary arteries. It typically leads to right-sided heart failure and death within 5 to 7 years of diagnosis.

While right ventricular dysfunction occurs independently of elevated blood pressure, all currently approved treatments for PAH target the pulmonary vessels instead of the heart dysfunction that is more likely to be the cause of death in affected patients.

However, for more than 40 years the cornerstone of therapy for left-sided heart failure has been to target left ventricular dysfunction with beta blockers. The use of beta blockers in patients with PAH has not been widely studied, perhaps due to mostly anecdotal concerns of decreased functional lung capacity.

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

In a double-blind, randomized study, Cleveland Clinic investigators assessed the use of carvedilol use in a group of 30 patients with PAH. Participants received either placebo, low fixed-dose, or escalating doses of carvedilol during the 6-month trial.

Results showed that carvedilol lowered heart rates in correlation with the dose, improved heart rate recovery from exercise, and did not worsen heart failure or lead to airflow deterioration. This suggests that carvedilol is safe in patients with PAH for 6 months, with evidence of improved outcomes that could prevent right-sided heart failure.

“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 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.”

The study was supported by NIH grants, and in part by the National Center for Advancing Translational Sciences.

To read more about the study, click here.