Carvedilol therapy significantly reduced plasma endothelin-1 levels (-2.1 vs 2.2 pg/ml; p<0.05) compared to placebo, correlating with functional and hemodynamic improvements in heart failure.
RCT (n=15)
Double-blind
2:1
Does carvedilol reduce plasma endothelin-1 levels, and do these changes reflect clinical response in patients with moderate to severe chronic heart failure?
Changes in plasma endothelin-1 levels correlate with functional and hemodynamic improvements, suggesting it may be a useful noninvasive marker of clinical response to beta-blocker therapy in chronic heart failure.
Absolute Event Rate: -2.1% vs 2.2%
p-value: p=< 0.05
Plasma levels of endothelin-1 are elevated in patients with chronic heart failure; however, it is unknown whether changes in plasma endothelin-1 levels accurately reflect clinical response to therapy in these patients. To determine this, we measured plasma endothelin-1 in addition to functional, hemodynamic, and other neurohormonal parameters as part of a double-blind, placebo-controlled study of the beta-blocker vasodilator carvedilol in patients with moderate to severe chronic heart failure. Patients were assigned (2:1 randomization) to receive carvedilol (25 mg twice daily, n = 10) or placebo (n = 5) for 14 weeks, with evaluations made before and after therapy. Compared to patients receiving placebo, patients receiving carvedilol improved significantly as assessed by the parameters described. These changes were paralleled by significant falls in endothelin-1 with carvedilol (-2.1 + 3.8 pg/ml) in comparison to placebo (2.2 + 3.9 pg/ml; p < 0.05 for between-group differences). Changes in endothelin-1 after treatment in both groups correlated significantly with changes in symptom severity, New York Heart Association class, 6-minute walk distance (r = 0.64 to 0.80; p < 0.05), hemodynamic parameters (ejection fraction, right atrial pressure, pulmonary artery diastolic pressure, pulmonary wedge pressure, right atrial pressure, and stroke volume index; r = 0.54 to 0.86; p < 0.05), and neurohormonal parameters (serum aldosterone and plasma norepinephrine (r = 0.74 to 0.76; p < 0.05). By stepwise regression analysis, change in endothelin-1 was an independent, noninvasive predictor of functional and hemodynamic responses to therapy in these patients. These findings suggest that endothelin-1 accurately reflects functional, hemodynamic, and neurohormonal responses to beta-blocker therapy in patients with congestive heart failure. Measurement of endothelin-1 may therefore be a useful, noninvasive approach to the evaluation of clinical response to drug therapy in these patients.
Krum et al. (1996) conducted an RCT in moderate to severe chronic heart failure (n=15). carvedilol vs. placebo was evaluated on Changes in plasma endothelin-1 levels (p=< 0.05). Carvedilol therapy significantly reduced plasma endothelin-1 levels (-2.1 vs 2.2 pg/ml; p<0.05) compared to placebo, correlating with functional and hemodynamic improvements in heart failure.