Key result
Low-dose carvedilol for 1 week significantly reduced right ventricular systolic pressure by an average of 13 mmHg compared to baseline in patients with pulmonary hypertension.
Why the study?
Following evidence of safety and possible benefit of carvedilol in PAH-associated right heart failure over 6 months, this study evaluated the short-term cardiovascular effects and early mechanistic biomarkers of carvedilol therapy.
Does low-dose carvedilol improve right ventricular systolic pressure and endothelial function biomarkers in patients with pulmonary hypertension?
Cohort (n=42)
Open-label
Yes
Does low-dose carvedilol improve right ventricular systolic pressure and endothelial function biomarkers in patients with pulmonary hypertension?
A 1-week trial of low-dose carvedilol in pulmonary hypertension can identify a responder phenotype characterized by a significant drop in right ventricular systolic pressure and better baseline endothelial function.
Short-term carvedilol may identify RVSP responders in pulmonary hypertension; extends beta-blocker data but leaves durability and outcomes open.
Background: The therapeutic benefits of β-blockers are well established in left heart failure. The Pulmonary Arterial Hypertension Treatment with Carvedilol for Heart Failure [PAHTCH] study showed safety and possible benefit of carvedilol in pulmonary arterial hypertension (PAH) associated right heart failure over 6 months. This study aims at evaluating the short-term cardiovascular effects and early mechanistic biomarkers of carvedilol therapy. Methods: Thirty patients with pulmonary hypertension (PH) received low dose carvedilol (3.125 mg twice daily) for 1 week prior to randomization to placebo, low-dose or dose-escalating carvedilol therapy. Echocardiography was performed at baseline and 1 week. Exercise capacity was assessed by 6-minute walk distance (6MWD). The L-arginine/ nitric oxide pathway and other biological markers of endothelial function were measured. Results: All participants tolerated one week of carvedilol without adverse effects. After 1 week of carvedilol, 6MWD and heart rate at peak exercise did not vary (both p > 0.1). Heart rate at rest and 1-minute post walk dropped significantly (both p < 0.05) with a trend for increase in heart rate recovery (p = 0.08). Right ventricular systolic pressure (RVSP) decreased by an average of 13mmHg (p = 0.002). Patients who had a decrease in RVSP of more than 10mm Hg were defined as responders (n = 17), and those with a lesser drop as non-responders (n = 13). Responders had a significant drop in pulmonary vascular resistance (PVR) after one week of carvedilol (p = 0.004). In addition, responders had a greater decrease in heart rate at rest and 1-minute post walk compared to non-responders (both p < 0.05). Responders had higher plasma arginine and global bioavailability of arginine at baseline compared to non-responders (p = 0.03 and p = 0.05 respectively). After one week of carvedilol, responders had greater increase in urinary nitrate (p = 0.04). Responders treated with carvedilol had a sustained drop in RVSP and PVR after 6 months of carvedilol with no change in cardiac output. Conclusions: Low-dose carvedilol for one week can potentially identify a PH responder phenotype that may benefit from β-blockers that is associated with less endothelial dysfunction.
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Cheong et al. (2018) conducted a cohort in Pulmonary Hypertension (n=42). Carvedilol vs. Baseline was evaluated on Right ventricular systolic pressure (RVSP) (-13 mmHg, p=0.002). Low-dose carvedilol for 1 week significantly reduced right ventricular systolic pressure by an average of 13 mmHg compared to baseline in patients with pulmonary hypertension.
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