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

Background Initiation of beta-blocker therapy is often limited by worsening congestive heart failure, which may manifest as worsening hemodynamics. De leterious hemodynamic effects might be mitigated with the vasodilation of c ombined calcium channel/beta-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 thera py for mild to severe heart failure. Functional, exercise, and hormonal sta tus 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. M ean election fraction at baseline was 13.4% +/- 5.7%; 79% of patients had h eart failure classified as New York Heart Association class III, and 66% ha d 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 reg imens produced significant increases in systemic vascular resistance and si gnificant decreases in cardiac output and index and stroke volume and strok e 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 signi ficant decreases in heart rate, systemic vascular resistance, and pulmonary capillary wedge pressure and significant increases in cardiac output and i ndex and stroke volume and stroke work indexes. Combination therapy produce d significant long-term decreases in blood pressure. Conclusions There was no further measurable benefit with the addition of am lodipine to metoprolol compared with the effects of metoprolol alone. Thera py with metoprolol alone and the combination of metoprolol and amlodipine w as well tolerated in patients with mild to severe heart failure, as evidenc ed by a lack of adverse effects on hemodynamic parameters over the short te rm and clinical and hemodynamic improvement with long-term treatment.