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Beta Blockade Reduces Heart Rate the Most in Sickest Heart Failure Patients But Does Not Increase Overall Survival: Presented at AHA

By Ed Susman

ORLANDO, FL -- November 10, 2003 -- Researchers probing the results of the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF) say that agent lowers heart rate the most in the sickest patients.

But that reduced resting heart rate does not translate to the greater reduction in mortality generated overall in the landmark study, said John Wikstrand, MD, Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden, and a senior medical adviser in clinical sciences at AstraZeneca.

"There is not a simple relationship between the reduction in heart rate and risk reduction in heart failure patients," Dr. Wikstrand said in his oral presentation here on November 10^th at the American Heart Association's Scientific Sessions 2003.

Dr. Wikstrand and colleagues reviewed the data accumulated in the MERIT-HF study and divided the 3,991 patients into quintiles based on their resting heart rate at study entry. For treatment randomization, 1,990 were assigned to metoprolol and 2,001 to placebo.

To analyze the risk reducing effect of metoprolol CR/XL within each quintile independent of baseline differences, the researchers performed Cox proportional regression analysis.

They found that in quintiles 1-4, the heart rate lowering results were similar. However, the metoprolol patients had a decrease in heart rate from 97 to 75 beats per minute (BPM), which was statistically different from the lowest quintile, which had a decrease in heart rate from 70 to 63 BMP after treatment. The net reduction -- taking into account placebo effects -- resulted in a 14-BMP reduction in the highest quintile.

While Dr. Wikstrand was able to demonstrate that treatment with metoprolol resulted in a reduced heartbeat when compared with placebo, the overall benefit did not differ among the quintiles in metoprolol patients. He noted that the mortality reduction of 41% in the lowest quintile was the same as the 41% reduction in the highest quintile.

He suggested that scientists might have predicted that the greater reduction in heart rate would correlate with a greater reduction in mortality among those patients, generally seen as the sickest of the heart failure patients in the study. But that correlation was not elucidated from the data, he said.

Although the study did not examine exercise heart rate among the nearly 4,000 patients in the study, Dr. Wikstrand, in responded to questions, said, "I am convinced we would see the same pattern."

He also noted that patients in the highest heart rate quintile were also able to tolerate the highest dose of metoprolol -- about 166 mg. The target dose was 200 mg. The lowest dose was taken by those with the lowest heart rate. Dr. Wikstrand suggested that doctors were reluctant to up-titrate the patients in the lowest quintile in fear that heart rate would be reduced too far.


[Study title: Resting Heart Rate and Mortality and Hospitalizations in Chronic Heart Failure Experiences from MERIT-HF. Abstract 1724]

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