All concepts, explanations, trials, and studies have been re-written in plain English and may contain errors. I am not a doctor ----------------------------------------------------------- Source: Basic Res Cardiol 2000;95 Suppl 1:I98-103 Title: MERIT-HF mortality and morbidity data. Authors: Hjalmarson A, Fagerberg B. INTRODUCTION: This study tested whether the beta-1-blocker metoprolol CR/XL (Toprol XL) added to standard CHF therapy reduces mortality symptoms in patients with low ejection fractions. This was a double-blind randomized study with 3991 class 2-4 patients having ejection fraction less than 40%, stable on standard therapy. Toprol XL dose was raised over 8 weeks starting at 12.5mg in class 3-4 patients and at 25mg in class 2 patients. Target dose was 200mg once daily. Primary endpoints were all-cause mortality and combined all-cause mortality plus hospitalization. Also gathered was cause-specific data on hospitalization, heart class and quality of life. Average follow-up was one year. FINDINGS: All-cause mortality was reduced in the Toprol XL group compared to the placebo group. A) 145 patient deaths in the Toprol XL group B) 217 patient deaths in the placebo group There were less sudden deaths in the metoprolol group (79 versus 132 deaths in the placebo group). There were fewer deaths from worsening heart failure in the metoprolol group (30 versus 58 deaths in the placebo group). Total mortality or hospitalizations due to worsening heart failure was reduced (311 versus 439 events in the placebo group). There were fewer hospitalizations due to worsening heart failure (317 versus 451 in the placebo group) and fewer days in the hospital due to worsening heart failure (3401 versus 5303 days in the placebo group). There was also an improvement in heart class. More patients taking placebo quit due to adverse effects. CONCLUSIONS: In CHF patients metoprolol CR/XL once per day improved survival by 34%, sudden death by 41%, and deaths from worsening heart failure by 49%. In addition to improved survival, there were also fewer hospitalizations for worsening heart failure, improved heart class and quality of life. Metoprolol XL was well tolerated. PMID: 11192362 =========================================================== Source: JAMA 2000 Mar 8;283(10):1295-302 Title: The Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT-HF) Authors: MERIT-HF Study Group. Comments in: ACP J Club. 2000 Sep-Oct;133(2):46 JAMA. 2000 Jul 26;284(4):436; discussion 436-7 JAMA. 2000 Mar 8;283(10):1335-7 INTRODUCTION: This study tested the effects of controlled-release metoprolol on total mortality, hospitalizations, symptoms, and quality of life in heart failure patients. This was a randomized, double-blind controlled trial, done from February 14, 1997 to October 31, 1998. Average follow-up was one year. Three hundred thirteen centers in 14 countries participated, using 3991 class 2-4 heart failure patients. Ejection fraction was 40% or less and patients were taking standard CHF therapy. Class 2 patients started at 25mg metoprolol CR/XL once per day. Class 3-4 patients started at 12.5mg per day. Dose was raised to a target dose of 200mg once per day in 1,990 patients while 2,001 patients took placebo. Quality of life was measured in a substudy of 741 patients. All endpoints were improved in the metoprolol group. Total mortality or all-cause hospitalizations was 641 versus 767 events in the placebo group - a risk reduction of 19%. Total mortality or hospitalizations for worsening heart failure were 311 versus 439 events in the placebo group - a risk reduction of 31%. Hospitalizations for worsening heart failure were 317 versus 451 in the placebo group. Days in the hospital for worsening heart failure were 3401 versus 5303 days in the placebo group. Heart class improved in the metoprolol CR/XL group. CONCLUSIONS: In this study of patients with symptomatic heart failure, metoprolol CR/XL improved survival, reduced hospitalizations for worsening heart failure, improved heart class, and improved patient quality of life. PMID: 10714728 =========================================================== Source: J Am Coll Cardiol 2000 Dec;36(7):2072-80 Title: Antiremodeling effects on the left ventricle during beta-blockade with metoprolol in the treatment of chronic heart failure. Authors: Groenning BA, Nilsson JC, Sondergaard L, Fritz-Hansen T, Larsson HB, Hildebrandt PR. INTRODUCTION: This study tested the effects of the beta1-blocker Toprol XL on left ventricular size and function in heart failure patients. This was a randomized, placebo-controlled, double-blind substudy to MERIT-HF. Forty-one patients were examined by MRI 3 times in a 6-month period, measuring left ventricle size and function. Both end-diastolic volume (150 ml/m2 to 126 ml/m2 after 6 months) and end-systolic volume (107 ml/m2 to 81 ml/m2) went down. Ejection fraction increased in the metoprolol CR/XL group from 29% to 37%. No changes were seen in the placebo group. Left ventricle mass went down in both groups. CONCLUSIONS: This study shows that the beta1-blocker metoprolol CR/XL fights heart remodeling (enlargement) in CHF patients. PMID: 11127443 ============================================================ Source: Lancet 1999 Jun 12;353(9169):2001-7 Title: Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF) Comment in: ACP J Club. 2000 Jan-Feb;132(1):3 Lancet. 1999 Jun 12;353(9169):1988-9 Lancet. 1999 Oct 23;354(9188):1471-2 INTRODUCTION: This study tested whether metoprolol CR/XL taken once daily, in addition to standard therapy, would lower mortality in CHF patients. This was a a double-blind, randomised, controlled study. We enrolled 3991 class 2-4 heart failure patients with ejection fraction of 40% or less on standard therapy. Class 3-4 patients started at 12.5mg Toprol XL while class 2 patients started at 25mg once daily. Toprol XL was taken by 1,990 patients and placebo was taken by 2,001 patients. Target dose was 200mg once daily. Primary endpoint was all-cause mortality. The study was stopped early. Average follow-up was one year. All-cause mortality was lower in the beat-blocker group (145 versus 217 deaths in the placebo group). There were fewer sudden deaths in the beta-blocker group (79 versus 132 in the placebo group). There were fewer deaths from worsening heart failure in the beta-blocker group (30 versus 58 in the placebo group). CONCLUSIONS: Metoprolol CR/XL once daily added to standard therapy improved survival. The drug was well tolerated. PMID: 10376614