A study, “Pulmonary arterial hypertension treatment with carvedilol for heart failure: a randomized controlled trial,” published in the journal JCI Insights, concluded that carvedilol improved heart rate recovery and reduced right ventricular (RV) metabolic rate.
Carvedilol, a beta blocker, is known to reverse cardiac remodeling and improve overall cardiac outcomes. Although scientists don’t fully understand its mechanism of action, the use of carvedilol or other beta blockers does reduce mortality in heart failure patients.
The U.S. Food and Drug Administration (FDA) approved carvedilol in 1995 to treat chronic heart failure, left ventricular dysfunction and hypertension. Despite its demonstrated therapeutic potential, the use of such medicines to treat PAH and right ventricular failure had not been fully addressed.
“There is a critical need for new therapies to support right ventricular function in pulmonary hypertension,” Dr. Serpil C. Erzurum, chair of the Cleveland Clinic Lerner Research Institute and the study’s senior author, said in a news release. “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,” Erzurum said of the study, which was supported by the National Institutes of Health and the National Center for Advancing Translational Sciences.
In the PAHTCH trial (NCT01586156), Cleveland Clinic researchers enrolled 30 PAH patients with diagnosed stable, chronic, mild to severe heart failure and randomly assigned them to one of the three study arms. The patients received either 3.125 mg of carvedilol twice daily; carvedilol in a dose escalation plan – 3.125 mg, 6.25 mg, 12.5 mg and 25 mg twice daily, one dose per week — or a placebo for up to six months.
Carvedilol was found to be safe and well tolerated. The treatment didn’t worsen the patients’ heart condition or their respiratory capacity, and no serious adverse effects were reported during the study time frame. It did induce a reduction in heart rate correlated with drug dosage. It also improved heart rate recovery from exercise. Taken together, these findings suggest that carvedilol can be used to prevent right heart failure progression in PAH patients.
“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,” said study co-author Dr. W.H. Wilson Tang, an advanced heart failure and transplant cardiologist at Cleveland Clinic. “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.”