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Beta-blockers safely benefit patients with PAH
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Patients with pulmonary arterial hypertension who were treated with carvedilol had improved outcomes, according to a study published in JCI Insight.
“New therapies for right-sided heart failure and PAH have lagged behind left-sided heart failure, so there is vital need for new treatments,” W. H. Wilson Tang, MD, director of the Center for Clinical Genomics at the Cleveland Clinic, told Cardiology Today. “The fact that beta-blockers were well-tolerated and effective in lowering heart rates thereby improved the heart efficiency is a key observation, since doctors have been cautioned against using them in this setting for safety concerns. This study provided important new data that advances our knowledge of using this class of drugs in this chronic and life-threatening lung-associated vascular disease.”
Stabilized pulmonary hypertension
Samar Farha, MD, associate staff in the Respiratory Institute at the Cleveland Clinic, and colleagues analyzed data from 30 patients with PAH who were stabilized on pulmonary hypertension medications 30 days before enrollment. Patients monitored their BP at home during a 1-week run-in phase before being randomly assigned to dose-escalating carvedilol to the maximum-tolerated dose of 25 mg twice per day (n = 10; mean age, 53 years; 60% women), 3.125 mg carvedilol twice per day (n = 10; mean age, 42 years; 70% women) or placebo (n = 10; mean age, 38 years; 80% women). The medication was administered for 24 weeks.
Follow-up involved weekly phone calls and periodic weekly visits to monitor clinical status, evaluate adverse effects and collect outcome data.
Researchers also analyzed data from a control group (n = 12; mean age, 42 years; 83% women) for comparison.
The primary endpoint was the assessment of myocardial glucose uptake during fasting-gated fluorodeoxyglucose-PET. Secondary endpoints included changes in assessments such as echocardiographic parameters and 6-minute walk distance.
Patients assigned carvedilol had reduced heart rate. After adjusting for age, heart rate remained low in the dose-escalating carvedilol group vs. placebo at 1 month (P = .05) and 3 months (P = .07). Heart rate correlated with the dosage of carvedilol at 1 month (P = .006) and 3 months (P = .04).
Systolic BP decreased from baseline (122 mm Hg) in patients assigned carvedilol at the 1-month (114 mm Hg; P = .04) and 3-month follow-up visits (112 mm Hg; P = .08). Diastolic BP also decreased from baseline (81 mm Hg) at 1 month (71 mm Hg; P = .05) and 3 months (73 mm Hg; P = .03).
Effects on exercise
Six-minute walk distance did not differ among all three groups. Patients in the dose-escalating group had decreased heart rates at peak exercise and 1 minute after exercise. At 3 months, those in the low-fixed-dose group had increased heart rate recovery (36 beats per minute) vs. the placebo group (12 beats per minute; P = .03). After adjusting for age, there was still a difference (P = .01).
Patients in the dose-escalating group had a reduction in right ventricular glycolytic rate and an increase in beta-adrenergic receptor.
Right ventricular function was stable and cardiac output was maintained in patients assigned carvedilol.
“Longer-term studies are needed, but this is important progress in our efforts to find successful treatment for this debilitating lung disease,” Tang told Cardiology Today. – by Darlene Dobkowski
For more information:
W. H. Wilson Tang, MD, can be reached at tangw@ccf.org.
Disclosures: The authors report no relevant financial disclosures.
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