Effects of carvedilol on plasma B-type natriuretic peptide concentration and symptoms in patients with heart failure and preserved ejection fraction

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Abstract

Although the benefits of carvedilol in patients with heart failure and depressed ejection fraction (EF) have been elucidated, those in patients with preserved EF are not understood. We enrolled 40 patients with mild or moderate heart failure and EF ≥45%. They were randomly assigned to carvedilol (n = 19) or conventional therapy (n = 21). After 12 months of treatment, carvedilol significantly improved all end points (plasma concentration of B-type natriuretic peptide [BNP] from 175 (35 to 209) to 106 (52 to 160) pg/ml, mean (95% confidence interval) p <0.01; New York Heart Association functional class from 2.37 (2.13 to 2.61) to 1.56 (1.21 to 1.91), p <0.01; exercise capacity estimated with the Specific Activity Scale from 4.75 (4.50 to 5.00) to 5.68 (5.22 to 6.14) METs, p <0.02), whereas conventional therapy did not (plasma BNP concentration from 150 (114 to 186) to 174 (100 to 248) pg/ml; New York Heart Association functional class from 2.29 (2.08 to 2.50) to 2.11 (1.73 to 2.49); exercise capacity from 4.57 (4.34 to 4.80) to 4.72 (4.41 to 5.03) METs). Univariate regression analyses showed that only the use of carvedilol was correlated with the decrease in plasma BNP concentration (p <0.03). Multivariate analyses demonstrated that an ischemic cause of heart failure (p <0.02), high plasma concentration of BNP (p <0.02), left ventricular dilation (p <0.03), and use of carvedilol (p <0.04) at baseline were predictive of a decrease in plasma concentration of BNP. In conclusion, carvedilol potentially decreased neurohumoral activation, decreased symptoms, and increased exercise capacity in patients with heart failure and preserved EF.

Section snippets

Patients

We initially enrolled 48 consecutive outpatients referred to our heart failure clinic at Nagoya City University Hospital from April 1, 2000 to March 31, 2001, due to heart failure according to New York Heart Association (NYHA) functional class II or III and stage C of American College of Cardiology/American Heart Association guidelines for the evaluation and management of chronic heart failure in the adult.6 All patients met Framingham criteria for diagnosis of heart failure. LVEF, as assessed

Patient characteristics

There was no significant difference in baseline characteristics and treatment of patients between groups as listed in Table 1. Mean dosage of carvedilol at the end of the study was 10.9 mg/day (10.0, 77 to 14.0). Each patient using an angiotensin-converting enzyme inhibitor received 5 mg/day of enalapril. No patient received >80 mg/day of furosemide or >16 mg/day of torsemide. We administered 80 mg/day of valsartan to 2 patients on conventional therapy in whom treatment had failed.

Treatment failure and tolerability

Treatment

Discussion

In the present study, the addition of carvedilol to conventional therapy for 12 months decreased plasma BNP concentrations, alleviated symptoms, and increased exercise capacity in patients with heart failure and LVEF ≥45%. Treatment with carvedilol was tolerated as well as conventional therapy. Effects of β-adrenergic blockers in patients with preserved EF have not been tested in randomized trials except for the Swedish Evaluation of Diastolic Dysfunction in Congestive Heart Failure (SWEDIC),

References (25)

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