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Minimal dose for effective clinical outcome and predictive factors for responsiveness to carvedilol: Japanese chronic

Hiroshi Okamoto1, Masatsugu Hori, Masunori Matsuzaki

  • 1Department of Cardiovascular Medicine, National Hospital Organization, Hokkaido Medical Center, Sapporo, Japan. okamotoh@med.hokudai.ac.jp

International Journal of Cardiology
|December 19, 2012
PubMed

Insights

Minimal carvedilol doses effectively manage chronic heart failure (CHF) by reducing heart rate (HR) and BNP, not just by dose. Early reductions in HR and BNP predict long-term outcomes in CHF patients.

Area of Science:

  • Cardiology
  • Pharmacology
  • Genetics

Background:

  • Optimal beta-blocker dosing for chronic heart failure (CHF) survival benefits remains unclear.
  • Predictive parameters for morbidity and mortality in CHF patients require identification.

Purpose of the Study:

  • To determine the minimal effective dose of carvedilol for survival benefits in Japanese CHF patients.
  • To identify the best predictive parameter for effective outcomes in CHF treatment.

Main Methods:

  • A prospective, randomized trial involving 364 mild to moderate CHF patients.
  • Patients received daily carvedilol doses of 2.5, 5, or 20mg alongside standard therapy.
  • A 3-year follow-up assessed clinical outcomes, echocardiographic parameters, and genetic polymorphisms.

Main Results:

  • Carvedilol reduced resting heart rate (HR) and B-type natriuretic peptide (BNP) with dose-response in the early period.
  • Left ventricular ejection fraction (LVEF) increased and left ventricular diastolic diameter (LVDd) decreased, without dose-response.
  • No significant difference in the primary endpoint (mortality/hospitalization); however, early HR and BNP reductions predicted outcomes, and adverse events were dose-dependent.
  • Osteopontin (OPN) genotype G-156 del was associated with event-free survival.

Conclusions:

  • Low-dose carvedilol is effective when HR and/or BNP are reduced, guiding therapy by these markers, particularly initial HR reduction.
  • Carvedilol dosage should be guided by physiological response (HR, BNP) rather than solely by dose.
  • Osteopontin (OPN) may serve as a genetic marker for predicting long-term event-free survival in CHF.
Abstract

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