Efficacy and safety of carvedilol in treatment of heart failure with chronic kidney disease: A meta-analysis of randomized trials

Ravinder K. Wali, Malini Iyengar, Gerald J. Beck, David M. Chartyan, Michel Chonchol, Mary Ann Lukas, Christopher Cooper, Jonathan Himmelfarb, Matthew R. Weir, Tomas Berl, William L. Henrich, Alfred K. Cheung

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Background-The safety and efficacy of different types ofβ-blocker therapy in patients with non-dialysis-dependent chronic kidney disease (CKD) and systolic heart failure (HF) are not well described. We assessed whether treatment of systolic HF with carvedilol is efficacious and safe in adults with CKD. Methods and Results-We performed a post hoc analysis of pooled individual patient data (n=4217) from 2 multinational, double-blinded, placebo-controlled, randomized trials, CAPRICORN (Carvedilol Postinfarct Survival Control in Left Ventricular Dysfunction Study) and COPERNICUS (Carvedilol Prospective Randomized, Cumulative Survival study). Primary outcome was all-cause mortality. Secondary outcomes included cardiovascular mortality, HF mortality, first HF hospitalization, the composite of cardiovascular mortality or first HF hospitalization, and sudden cardiac death. Non-dialysis-dependent CKD was defined by estimated glomerular filtration rate ≤60 mL/min/1.73 m 2, using the abbreviated Modification of Diet in Renal Disease equation. CKD was present in 2566 of 4217 (60.8%) of the cohort, 50.4% of whom were randomly assigned to carvedilol therapy. Within the CKD group, treatment with carvedilol decreased the risks of all-cause mortality (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.63 to 0.93; P=0.007), cardiovascular mortality (HR, 0.76; 95% CI, 0.62 to 0.94; P=0.011), HF mortality (HR, 0.68; 95% CI, 0.52 to 0.88; P=0.003), first hospitalization for HF (HR, 0.74; 95% CI, 0.61 to 0.88; P=0.0009), and the composite of cardiovascular mortality or HF hospitalization (HR, 0.75; 95% CI, 0.65 to 0.87; P<0.001) but was without significant effect on sudden cardiac death (HR, 0.76; 95% CI, 0.56 to 1.05; P=0.098). There was no significant interaction between treatment arm and study type. Carvedilol was generally well tolerated by both groups of patients, with an increased relative incidence in transient increase in serum creatinine without need for dialysis and other electrolyte changes in the CKD patients. However, in a sensitivity analysis among HF subjects with estimated glomerular filtration rate <45 mL/min/1.73 m2 (CKD stage 3b), the efficacy of carvedilol was not significantly different from placebo. Conclusions-This analysis suggests that the benefits of carvedilol therapy in patients with systolic left ventricular dysfunction with or without symptoms of HF are consistent even in the presence of mild to moderate CKD. Whether carvedilol therapy is similarly efficacious in HF patients with more advanced kidney disease requires further study. (Circ Heart Fail. 2011;4:18-26.)

Original languageEnglish (US)
Pages (from-to)18-26
Number of pages9
JournalCirculation: Heart Failure
Volume4
Issue number1
DOIs
StatePublished - Jan 1 2011

Keywords

  • Carvedilol
  • Chronic heart failure
  • Chronic kidney disease
  • Meta-analysis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Efficacy and safety of carvedilol in treatment of heart failure with chronic kidney disease: A meta-analysis of randomized trials'. Together they form a unique fingerprint.

  • Cite this

    Wali, R. K., Iyengar, M., Beck, G. J., Chartyan, D. M., Chonchol, M., Ann Lukas, M., Cooper, C., Himmelfarb, J., Weir, M. R., Berl, T., Henrich, W. L., & Cheung, A. K. (2011). Efficacy and safety of carvedilol in treatment of heart failure with chronic kidney disease: A meta-analysis of randomized trials. Circulation: Heart Failure, 4(1), 18-26. https://doi.org/10.1161/CIRCHEARTFAILURE.109.932558