Short-term and long-term hemodynamic and clinical effects of metoprolol alone and combined with amlodipine in patients with chronic heart failure

• Published in: The American heart journal Vol. 138; no. 2; pp. 261 - 268
• Main Authors: Kukin, Marrick L., Freudenberger, Ronald S., Mannino, Michael M., Kalman, Jill, Steinmetz, Marilyn, Buchholz-Varley, Cathleen, Ocampo, Ofelia N.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01-08-1999; Elsevier
• Subjects: Adrenergic beta-Antagonists - pharmacology; Adrenergic beta-Antagonists - therapeutic use; Adult; Amlodipine - pharmacology; Amlodipine - therapeutic use; Biological and medical sciences; Calcium Channel Blockers - pharmacology; Calcium Channel Blockers - therapeutic use; Cardiotonic agents; Cardiovascular system; Drug Therapy, Combination; Female; Heart Failure - drug therapy; Heart Failure - physiopathology; Hemodynamics - drug effects; Humans; Male; Medical sciences; Metoprolol - pharmacology; Metoprolol - therapeutic use; Middle Aged; Pharmacology. Drug treatments; Prospective Studies; Time Factors; Treatment Outcome; Vascular Resistance - drug effects; Human; Heart failure; Drug combination; Cardiotonic agent; Metoprolol; Treatment efficiency; Cardiovascular disease; Chemotherapy; Chronic; Treatment; Heart disease; Amlodipine; Dihydropyridine derivatives; Hemodynamics
• ISSN: 0002-8703; 1097-6744
• DOI: 10.1016/S0002-8703(99)70110-9

Background Initiation of β-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/β-blocker therapy.
Methods and 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. (Am Heart J 1999;138:261-8.)