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First-dose response to angiotensin-converting enzyme inhibition in congestive cardiac failure: a Malaysian experience
N T Navookarasu1, A R Rahman, I Abdullah
1Kuching General Hospital, Sarawak.
Insights
Angiotensin converting enzyme (ACE) inhibitors are underused due to fear of first-dose hypotension. Perindopril, unlike other ACE inhibitors, did not cause this side effect in patients with congestive heart failure.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Angiotensin converting enzyme (ACE) inhibitors are crucial for managing heart failure, reducing morbidity and mortality.
- Underuse of ACE inhibitors is partly attributed to concerns regarding first-dose hypotension.
Purpose of the Study:
- To evaluate the incidence of first-dose hypotension with various ACE inhibitors.
- To compare the hemodynamic effects of perindopril against other ACE inhibitors and placebo.
Main Methods:
- A double-blind, randomized, placebo-controlled study involving 80 patients with congestive heart failure.
- Patients were assigned to receive placebo, captopril, enalapril, perindopril, or lisinopril.
- Blood pressure monitoring was conducted over a 5-hour period post-drug administration.
Main Results:
- Perindopril (2 mg) did not significantly lower mean arterial pressure compared to placebo (drop of 5.29 mmHg vs 5.89 mmHg).
- Other ACE inhibitors (enalapril, lisinopril, captopril) caused significant drops in mean arterial pressure (13.28 mmHg, 15.04 mmHg, 16.76 mmHg, respectively).
- These significant drops were statistically different from placebo (p < 0.05).
Conclusions:
- Perindopril is a unique ACE inhibitor that does not induce first-dose hypotension in patients with congestive heart failure.
- This finding may help overcome a barrier to the wider clinical use of ACE inhibitors in heart failure management.
Abstract:
Despite their proven value in reducing morbidity and mortality in different grades of heart failure, angiotensin converting enzyme (ACE) inhibitors continue to be underused. One reason for this is clinicians' apprehension of first-dose hypotension. We conducted a double-blind, randomised, placebo-controlled parallel group study to investigate the effect of various ACE inhibitors on first-dose hypotension. Eighty unselected patients were randomised into five treatment groups: placebo, captopril 6.25 mg, enalapril 2.5 mg, perindopril 2 mg and lisinopril 2.5 mg. Blood pressure was measured at baseline, half hourly for two hours and hourly for three hours after drug treatment. The maximum drops in mean arterial pressure (in mmHg +/- SD) were placebo 5.89 +/- 2.65, perindopril 5.29 +/- 2.49, enalapril 13.28 +/- 3.31, lisinopril 15.04 +/- 5.74 and captopril 16.76 +/- 5.74 (all p < 0.05 vs placebo except for perindopril). Perindopril, unlike the other ACE inhibitors studied, did not produce first-dose hypotension following its initiation in patients with congestive heart failure.