title: Short-term and long-term hemodynamic and clinical effects of metoprolol alone and combined with amlodipine in patients with chronic heart failure.
abstract: BACKGROUND
  Initiation of beta-blocker therapy is often limited by worsening congestive heart failure, which may manifest as worsening hemodynamics. Deleterious hemodynamic effects might be mitigated with the vasodilation of combined calcium channel/beta-blocker therapy.
  
  
  RESULTS
  This prospective, randomized study assessed the safety and efficacy of metoprolol alone or combined with amlodipine on hemodynamic parameters at baseline, 2 hours after the first dose of study medication, and after 12 weeks of therapy in patients receiving background triple therapy for mild to severe heart failure. Functional, exercise, and hormonal status were assessed at baseline and end of study. Twenty-nine patients (mean age 50 +/- 12.1 years) were enrolled; 21 completed 12 weeks of treatment. Mean ejection fraction at baseline was 13.4% +/- 5.7%; 79% of patients had heart failure classified as New York Heart Association class III, and 66% had heart failure of idiopathic origin. Heart rate and blood pressure did not change with short-term therapy in either group. The first dose of both regimens produced significant increases in systemic vascular resistance and significant decreases in cardiac output and index and stroke volume and stroke work indexes; combination therapy acutely yielded small but statistically significant increases in pulmonary artery, pulmonary capillary wedge, and right atrial pressures. Long-term therapy with both regimens produced significant decreases in heart rate, systemic vascular resistance, and pulmonary capillary wedge pressure and significant increases in cardiac output and index and stroke volume and stroke work indexes. Combination therapy produced significant long-term decreases in blood pressure.
  
  
  CONCLUSIONS
  There was no further measurable benefit with the addition of amlodipine to metoprolol compared with the effects of metoprolol alone. Therapy with metoprolol alone and the combination of metoprolol and amlodipine was well tolerated in patients with mild to severe heart failure, as evidenced by a lack of adverse effects on hemodynamic parameters over the short term and clinical and hemodynamic improvement with long-term treatment.
authors.affiliation: Heart Failure Program, Cardiovascular Institute, Box 1030, Mount Sinai Schooll of Medicine, New York, NY 10029, USA. marrick.kukin@mssm.edu
authors.forename: M L
authors.initials: ML
authors.lastname: Kukin
authors.forename: R S
authors.initials: RS
authors.lastname: Freudenberger
authors.forename: M M
authors.initials: MM
authors.lastname: Mannino
authors.forename: J
authors.initials: J
authors.lastname: Kalman
authors.forename: M
authors.initials: M
authors.lastname: Steinmetz
authors.forename: C
authors.initials: C
authors.lastname: Buchholz-Varley
authors.forename: O N
authors.initials: ON
authors.lastname: Ocampo
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D017311:Amlodipine / Q000494:pharmacology* / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D017311:Amlodipine; D008790:Metoprolol