Use of carvedilol in patients with congestive heart failure 

Kevin P. O’Reilly, MD
EBM Conference
8 August 1997

Clinical Scenario:
A 61 year old white male with ischemic heart disease and systolic dysfunction (CHF) who, while on an optimal regimen of an ACE inhibitor, diuretic, and digoxin, continues to experience orthopnea and shortness of breath with usual daily activities. Would initiation of treatment with carvedilol benefit this patient ?

Clinical Bottom Lines:

(1) Following 19 months of follow-up in patients with ischemia-related CHF, carvedilol produced a statistically significant improvement in the combined endpoint of mortality and hospitalizations (p = 0.02) and borderline statistical significance in hospitalizations alone (p = 0.05).

(2) Following 12 months of treatment carvedilol provided some improvement in LV function with a 5.3% absolute increase in LVEF and a decrease in LV size as compared with placebo.

(3) Carvedilol did not improve symptoms of CHF or exercise tolerance in patients with ischemic heart disease.

The Evidence:

A randomized, double-blind, placebo-controlled trial conducted at 20 hospitals by the Australia / New Zealand Heart Failure Research Collaborative Group (Lancet 1997; 349: 375-380)

Comments:

(1) The study was well conducted with excellent randomization of patients between the treatment and control groups (excepting that the participants were 80% male).

(2) Carvedilol produced an improvement in LV function as seen in increased LVEF and decreased LV size and also decreased the risk of the combined event of death or hospitalizations (RRR=21%, ARR=13%, NNT=8; p = 0.02).

(3) Although carvedilol did decrease serious clinical events and improve LV function, it did not improve functional capacity (ETT duration or 6 minute walk distance) or symptoms as evaluated at 12 month follow-up. It should be noted that at 6 month follow-up there were significant trends toward worsening of the NYHA class (p = 0.05) and the SAS score (p = 0.02) with carvedilol compared with placebo. When using this drug one should remain aware of patients’ quality of life.

(4) Effects of carvedilol on hospitalization alone achieved borderline statistical significance (RRR=18%, ARR=10%, NNT=8; p = 0.05) and did not achieve significance for mortality alone (RRR=23.8%, ARR=3%, NNT=33; p > 0.1).

(5) Given the effects of carvedilol on CHF symptoms and the careful monitoring provided to the study patients there is some concern for the general use of carvedilol.

(6) Given the results, carvedilol most likely has some impact on mortality, however there have been too few deaths in carvedilol trials to allow accurate calculation of the drug’s effect on survival, therefore larger studies are needed.