Clinical research of large dosages of β-blocker (metoprolol) in treatment of heart failure

AIM: To compare the therapeutic effect of β-blockers at different dosages on heart failure (HF) patients and to elucidate the necessity of treating HF with target or maximum tolerance dosages of β-blockers. METHODS: A total of 182 patients with confirmed chronic HF were selected and divided randomly into normal-dosage group and high-dosage group. One hundred and sixty-two patients completed the study in which a daily dosage of 25 to 50 mg of metoprolol combined with basic therapy was administrated in normal-dosage group, whereas in high-dosage group, the dosage of metoprolol gradually increased until target or maximum tolerance dosage plus basic therapy. Clinical indexes in both groups (NYHA, heart rate, blood pressure, left ventricular end-diastolic dimension, left ventricular ejection fraction, plasma NE, BNP concentration and 6-min maximum walking distance) were compared after 12 weeks of metoprolol treatment of stable dosage. RESULTS: Eight-one patients completed the experiment in the high-dosage group with the final metoprolol dosage reaching (100±30)mg/day. Among the 81 patients, the metoprolol dosage was 75 mg/day for 36 patients (44.44%), 100 mg/day for 23 patients (28.40%), 125 mg/day for 12 patients (14.81%), 150 mg/day for 8 patients (9.88%), and 200 mg/day for 2 patients (2.47%). In the high-dosage group when compared before and after treatment, NYHA significantly improved, HR decreased from (85±9)l/min to (73±5)l/min, LVEF(%) increased from 41±4 to 44±5, NE(ng/L) decreased from 518±311 to 251±67, BNP(μg/L) decreased from 323±91 to 238±72, and the 6-min walking distance (m) increased from 331±49 to 339±44. Compared with those in normal dosage group, NYHA significantly improved whereas HR decreased from (83±9)l/min to (73±5)l/min, NE(ng/L) decreased from 389±286 to 251±67, and BNP(μg/L) decreased from 302±103 to 238±72. CONCLUSION: It is appropriate to use metoprolol to treat HF by gradually increasing the dosage and adjusting the dosage according to HR, BP, and HF indexes. Normal or high dosages of metoprolol improve cardiac remodeling, increase heart function and enhance exercise tolerance within 12 weeks but high dosages more efficiently control the HR. Large dosages of metoprolol inhibit the over activation of neural hormones, specifically in decreasing plasma NE and BNP concentration so as to improve its biological efficacy and ameliorate long-term prognosis of HF.