Key result
Adding carvedilol to digoxin improves LVEF and symptoms in CHF with AF despite unchanged BNP.
Why the study?
Does carvedilol improve BNP levels and cardiac function in patients with chronic heart failure and persistent atrial fibrillation?
RCT (n=47)
double-blind
randomised
Does carvedilol improve BNP levels and cardiac function in patients with chronic heart failure and persistent atrial fibrillation?
Absolute Event Rate: 28% vs -6%
p-value: p=0.11
In patients with CHF and persistent AF, carvedilol improves symptoms and cardiac function, but these clinical improvements are not reflected by changes in BNP levels.
Carvedilol addition to digoxin improves LVEF and symptoms in CHF with persistent AF; challenges BNP as a surrogate for clinical response.
OBJECTIVES: We sought to determine the relationship between changes in natriuretic peptides and symptoms as a consequence of introducing beta-blocker therapy, in patients with chronic heart failure (CHF) and persistent atrial fibrillation (AF). METHODS: In a randomised, double-blind, placebo-controlled study involving 47 patients with CHF and persistent AF (mean age 68 years and 62% men), we analysed the individual change (Δ) in B-type natriuretic peptide (BNP) level to the introduction of carvedilol (titrated to a target dose of 25 mg twice daily, group A) or placebo (group B) in addition to background treatment with digoxin. Symptoms score, 6-min walk distance, New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), heart rate (24-hour ECG) and BNP were measured at baseline and at 4 months. RESULTS: LVEF (Δ median +5 vs. +0.4, p = 0.048), symptoms score (Δ median -4 vs. 0, p = 0.04), NYHA class (Δ median -33% vs. +3% in NYHA class 3-4, p = 0.046) and heart rate [Δ median 24-hour ventricular rate (VR) -19 vs. -2, p < 0.0001] improved with combination therapy of digoxin and carvedilol compared to digoxin alone, but BNP (Δ median +28 vs. -6 , p = 0.11) trended in the opposite direction. There was no relationship between the degree of symptomatic improvement or VR control and BNP response. CONCLUSION: After the introduction of carvedilol, clinical outcome appears unrelated to BNP changes in patients with CHF and AF. Changes in BNP cannot be used as a marker of clinical response in terms of symptoms or cardiac function in this setting.
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Khand et al. (2015) conducted an RCT in chronic heart failure (CHF) and persistent atrial fibrillation (AF) (n=47). carvedilol vs. placebo was evaluated on Change in B-type natriuretic peptide (BNP) level (p=0.11). In patients with CHF and persistent AF, adding carvedilol to digoxin improved LVEF, symptoms, and heart rate, but clinical outcomes were unrelated to BNP changes (Δ median +28 vs. -6, p=0.11).
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