Cardioselective beta-blockade with atenolol and acebutolol following acute myocardial infarction: a multiple-dose haemodynamic comparison
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Beta-blockers like atenolol and acebutolol have unclear haemodynamic relevance in acute myocardial infarction patients. This study found no significant haemodynamic differences between them, suggesting intrinsic sympathomimetic activity may be irrelevant post-infarction.
Area of Science:
- Cardiology
- Pharmacology
Background:
- The haemodynamic impact of beta-blocker properties like cardioselectivity and intrinsic sympathomimetic activity (ISA) in acute myocardial infarction (AMI) patients is not fully understood.
- Beta-blocking drugs are crucial in managing AMI, but their ancillary properties require further investigation.
Purpose of the Study:
- To compare the dose-response haemodynamic effects of atenolol and acebutolol in patients with uncomplicated AMI.
- To determine if the intrinsic sympathomimetic activity (ISA) of acebutolol influences haemodynamics differently from the cardioselective effects of atenolol.
Main Methods:
- A single-blind, dose-response, crossover study was conducted in patients within 18 hours of AMI.
- Intravenous doses of atenolol (1-8 mg) and acebutolol (10-80 mg) were administered, achieving therapeutic plasma concentrations.
- Haemodynamic parameters including blood pressure, heart rate, cardiac output, and vascular resistance were measured.
Main Results:
- Both atenolol and acebutolol significantly decreased systolic blood pressure, heart rate, cardiac output, stroke volume, and stroke work index.
- Systemic vascular resistance increased with both drugs, while pulmonary artery occluded pressure showed varied responses.
- No statistically significant haemodynamic differences were observed between atenolol and acebutolol.
Conclusions:
- The intrinsic sympathomimetic activity (ISA) of acebutolol did not produce statistically significant haemodynamic differences compared to atenolol in AMI patients.
- This finding may indicate that acebutolol's ISA is insufficient or haemodynamically irrelevant given the heightened sympathetic tone post-AMI.
- Further research is needed to clarify the role of ISA in beta-blocker therapy for acute myocardial infarction.
Abstract:
In patients with acute myocardial infarction the haemodynamic relevance of the ancillary pharmacological properties of cardioselectivity and of intrinsic sympathomimetic activity (ISA) possessed by beta-blocking drugs is unclear. The dose-response effects of atenolol and acebutolol, two cardioselective compounds, the latter also possessing a degree of ISA, were therefore compared in a single-blind, dose-response, crossover study in patients within 18 h of suffering an uncomplicated acute myocardial infarction. The logarithmic cumulative dosage schedule achieved plasma concentrations in the clinical therapeutic ranges for both atenolol (0.05 +/- 0.04-0.19 +/- 0.03 micrograms/ml) and acebutolol (0.22 +/- 0.14-0.8 +/- 0.29 micrograms/ml). Incremental doses of intravenous atenolol (cumulative, 1-8 mg) resulted in significant decreases in systolic blood pressure, heart rate, cardiac output, stroke volume, and stroke work index (p less than 0.01 for each). Pulmonary artery occluded pressure (p less than 0.05) and systemic vascular resistance (p less than 0.01) increased. Incremental doses of intravenous acebutolol (cumulative, 10-80 mg) also resulted in significant decreases in systolic blood pressure, heart rate, cardiac output, stroke volume, and stroke work index (p less than 0.01 for each). Systemic vascular resistance increased (p less than 0.01); there was no consistent change in the pulmonary artery occluded pressure. Within the limits of the experimental protocol, the additional property of ISA possessed by acebutolol resulted in no statistically significant haemodynamic differences from atenolol. This may reflect either an insufficient degree of ISA possessed by acebutolol to confirm the original hypothesis, or its haemodynamic irrelevance in the presence of the increased sympathetic tone that is frequently present following acute myocardial infarction.