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Differences in first dose response to angiotensin converting enzyme inhibition in congestive heart failure: a placebo
R J MacFadyen1, K R Lees, J L Reid
1University Department of Medicine and Therapeutics, University of Glasgow.
Insights
This study compared initial responses to low-dose angiotensin converting enzyme inhibitors in elderly heart failure patients. Enalapril caused a prolonged blood pressure drop, while perindopril showed minimal hypotensive effects, suggesting differential acute responses.
Area of Science:
- Cardiology
- Pharmacology
- Geriatrics
Background:
- Chronic heart failure (CHF) is a prevalent condition in the elderly.
- Angiotensin converting enzyme inhibitors (ACEIs) are a cornerstone of CHF management.
- Understanding the acute hemodynamic effects of initiating ACEI therapy is crucial for patient safety.
Purpose of the Study:
- To compare the first-dose hemodynamic responses to low-dose captopril, enalapril, and perindopril in elderly patients with stable CHF.
- To assess differences in blood pressure, heart rate, and neurohormonal markers following initial ACEI administration.
Main Methods:
- A double-blind, randomized, placebo-controlled, parallel-group study.
- 48 elderly patients (58-85 years) with symptomatic stable CHF were enrolled.
- Patients received a single low oral dose of placebo, captopril (6.25 mg), enalapril (2.5 mg), or perindopril (2 mg).
Main Results:
- All ACEIs demonstrated varying degrees of blood pressure reduction and ACE inhibition.
- Captopril induced a rapid but transient fall in blood pressure.
- Enalapril resulted in a delayed, longer-lasting hypotensive effect associated with bradycardia.
- Perindopril showed minimal blood pressure changes, similar to placebo, despite comparable ACE inhibition to enalapril.
Conclusions:
- This study is the first to suggest qualitative differences in the acute response to structurally similar ACEIs like enalapril and perindopril.
- Low-dose perindopril appears to have a lower risk of causing acute hypotension in heart failure patients.
- The observed differences may be attributed to variations in local tissue angiotensin generation or other unelucidated mechanisms.
Objective:
To compare the first dose responses to low dose angiotensin converting enzyme inhibitors (captopril, enalapril, and perindopril) in elderly patients with stable chronic heart failure.
Design:
Double blind, randomised, placebo controlled, parallel, group prospective study of elderly patients with stable chronic heart failure.
Setting:
General hospital in-patient admissions for supervised diuretic withdrawal (24-48 hours) and the introduction of angiotensin converting enzyme inhibitor therapy.
Patients:
48 unselected elderly (58-85 years) patients with symptomatic but stable chronic heart failure (New York Heart Association grades II-IV) confirmed by clinical history, examination, and cardiological investigations. Patients gave their written and informed consent to receive their initial treatment under double blind conditions; blood pressure was monitored and blood samples taken to measure the pharmacokinetic and neurohormonal responses.
Intervention:
Patients were randomised to receive a daily oral dose of placebo, captopril (6.25 mg), enalapril (2.5 mg), or perindopril (2 mg).
Main Outcome Measures:
Blood pressure and heart rate responses, drug concentration, and plasma renin and ACE activities. Differences between treatment groups were analysed by analysis of variance.
Results:
The four randomised groups of patients had similar age, severity of heart failure (NYHA class), pretreatment diuretic dosage, plasma renin activity, and serum electrolyte state. Placebo treatment caused a modest but significant diurnal fall in blood pressure. Captopril produced a significant early (1.5 hours) and brief fall in blood pressure. The blood pressure fall with enalapril was later (4-10 hours), longer lasting, and was associated with significant slowing of supine heart rate. Though perindopril produced a similar plasma ACE inhibition to that produced by enalapril, it only caused changes in blood pressure that were similar to those caused by placebo.
Conclusions:
This controlled study is the first to indicate a qualitative difference in the acute response to angiotensin converting enzyme inhibitors with similar structure and metabolism (that is, enalapril and perindopril). Low dose perindopril seems to be less likely to cause hypotension in patients with heart failure. The explanation for the differences is unclear but may reflect differential effects on local tissue angiotensin generation.