Does open-label carvedilol titrated to the maximum dose improve long-term survival, left ventricular remodeling, and symptoms in heart failure patients?
Long-term carvedilol therapy in heart failure patients produces sustained improvements in left ventricular remodeling and symptoms, with particularly good long-term survival in patients with nonischemic etiology.
The authors measured long-term outcomes of patients who initiated carvedilol between 1990 and 1992 to test the hypothesis that carvedilol produces sustained benefits in heart failure patients. The study population consisted of 57 patients who completed a carvedilol placebo-controlled phase II trial. Patients were given open-label carvedilol and were titrated to the maximum dose. Patients were assessed by serial multigated acquisition, echocardiography, and symptom scores. Survival was assessed for all patients and censored as of January 1, 2004. Survival for ischemic vs nonischemic patients was compared using the log-rank test and further compared using Cox regression, controlling for covariates. Etiology of heart failure was ischemic in 15 patients and nonischemic in 42 patients. Median follow-up was 12.9 years. Resting left ventricular ejection fraction (LVEF) and heart failure symptom scores improved at 4 months of treatment and were sustained at 24 months. Left ventricular internal diameter in systole (LVIDS) and left ventricular internal diameter in diastole decreased significantly at 4 and 8 months, respectively, and LVIDS continued to improve at 24 months. Overall mortality was 43% in nonischemic patients and 73% in ischemic patients. In a multivariate analysis, ischemic etiology and baseline LVEF were significant predictors of mortality. Carvedilol produces sustained improvements in left ventricular remodeling and symptoms. Long-term survival is good, particularly in nonischemic patients.
MacGregor et al. (2009) studied this question.