Clinicians widely accept ACE inhibitors as first line therapy for CHF. ACE inhibitors have become first line therapy mainly because they were the first type of treatment to be evaluated in clinical trials. However, carvedilol may also be an acceptable first treatment for prevention of heart failure progression and reversal of remodeling.

The objective of the CARMEN trial was to challenge the prevailing practice of using ACE inhibitors as the mandatory first choice in this setting. Investigators compared carvedilol, enalapril and the combination of carvedilol and enalapril. Treatment continued for 18 months.

This parallel-group randomized study included 479 patients from 13 European countries. All patients had mild CHF, with left ventricular ejection fraction less than 40%. Most patients (65%) had NYHA Class II heart failure. The mean age was 62 years, and 81% were men.

Investigators assessed effect on left ventricular remodeling with transthoracic echocardiography at baseline, then at 6, 12 and 18 months. The primary endpoint of the study was change in this parameter from baseline to 18 months.

The following illustration shows that there was a significant improvement in left ventricular remodeling and function in the group of patients that received the combination of carvedilol and enalapril:

Furthermore, investigators observed reversal of left ventricular remodeling in patients who received carvedilol as monotherapy or in combination with enalapril. At 18 months, they saw an increase in left ventricular ejection fraction of approximately 3% in the combination group (p<0.001 versus baseline). These results did not occur in the enalapril monotherapy group.

Safety and tolerability was very similar in all three treatment groups. Serious adverse events occurred in 29% of patients in the carvedilol arm and in 28% of patients who received carvedilol plus enalapril. Adverse events leading to withdrawal occurred in 18% of patients in both groups. Dr. Remme added that there was no difference in tolerability between carvedilol and enalapril.

Dr. Remme said these results challenge the standard practice of prescribing an ACE inhibitor, then later prescribing a beta blocker if the patient remains symptomatic. Currently, guidelines in both the United States and Europe say that an ACE inhibitor should be first line treatment. Dr. Remme helped draft the 1997 and 2001 guidelines of the European Society of Cardiology. Now he thinks future guidelines should no longer state that ACE inhibitors need to be the first choice.

The results of this study give clinicians sufficient reason to consider using carvedilol or this combination as first line therapy, according to the investigator. Further research may show that first line carvedilol may produce better outcomes in certain patient populations.