MERIT-HF--description of the trial

The MERIT-HF study was a randomized, double-blind, placebo-controlled trial with a single-blind, two-week placebo run-in period. There were two primary objectives: total mortality; and the combined endpoint of total mortality or all-cause hospitalizations (time to first event). Several other combined endpoints were also predefined, as were number of hospitalizations due to heart failure and other cardiovascular causes, withdrawal of study medicine due to all causes, and due to worsening heart failure, and change in NYHA class. The effect on Quality of Life was assessed in a substudy. The major inclusion criteria were symptomatic heart failure for at least 3 months corresponding to NYHA class II-IV; and a left ventricular ejection fraction of 0.40 or less in 40 to 80 year old men and women. The patients had to be on optimal treatment for at least 2 weeks prior to randomization, defined in principle as any combination of diuretics and an ACE inhibitor. The recommended starting dose was half a 25 mg tablet of metoprolol CR/Zok once daily in patients in NYHA functional class III-IV, and one 25 mg tablet once daily in patients in NYHA class II. It was recommended to double the dose after each 2-week period in order to reach the highest tolerated dose aiming for a target dose level of 200 mg once daily of metoprolol CR/Zok or placebo. This dosage regimen could be modified according to the judgement of the investigator. Randomization began on February 14, 1997, and the last patient was randomized April 14, 1998. 1990 patients were randomized to metoprolol CR/Zok and 2001 to placebo. The International Steering Committee stopped the study by October 31, 1998, upon recommendation from the Independent Safety Committee. The second pre-planned interim analysis (50% point) had shown that the pre-defined criterion for termination of the study was met and exceeded. The mean follow-up time was 1 year.