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Acute anti-ischemic effects of perindoprilat in men with coronary artery disease and their relation with left
G L Bartels1, F M van den Heuvel, D J van Veldhuisen
1Sticares Cardiovascular Research Foundation, Rotterdam, The Netherlands.
Insights
Perindoprilat effectively reduces acute myocardial ischemia in patients with coronary artery disease. Its anti-ischemic effects are more pronounced in patients with left ventricular dysfunction, suggesting a potential therapeutic benefit.
Area of Science:
- Cardiology
- Pharmacology
- Cardiovascular Research
Background:
- Long-term angiotensin-converting enzyme (ACE) inhibition is known to reduce ischemic events in coronary artery disease (CAD).
- The acute anti-ischemic effects of ACE inhibition and its impact on patients with pre-existing left ventricular (LV) dysfunction remain unclear.
Purpose of the Study:
- To investigate the effects of perindoprilat on pacing-induced acute myocardial ischemia.
- To determine if left ventricular (LV) function influences the anti-ischemic properties of perindoprilat.
Main Methods:
- A double-blind trial involving 25 patients with exercise-induced ischemia.
- Patients received either perindoprilat (n=14) or placebo (n=11).
- Subgroups with and without LV dysfunction (LV ejection fraction <0.40) were analyzed within the perindoprilat group.
Main Results:
- Perindoprilat significantly blunted increases in systemic vascular resistance and LV end-diastolic pressure during pacing-induced ischemia.
- Perindoprilat inhibited ischemia-induced increases in norepinephrine uptake and reduced ST-segment depression by 32% compared to placebo.
- In patients with LV dysfunction, perindoprilat significantly reduced LV end-diastolic pressure by 67%, prevented myocardial lactate production, and showed greater inhibition of arterial norepinephrine increase.
Conclusions:
- Perindoprilat effectively reduces acute, pacing-induced myocardial ischemia in normotensive patients.
- The anti-ischemic benefits of perindoprilat are more pronounced in patients with left ventricular dysfunction compared to those with normal LV function.
Abstract:
Long-term angiotensin-converting enzyme (ACE) inhibition may reduce ischemic events in patients with coronary artery disease, but whether it protects against acute ischemia or the effects of preexisting left ventricular (LV) dysfunction on potential anti-ischemic properties is unknown. We performed a double-blind trial in 25 patients with exercise-induced ischemia. The effects of perindoprilat on pacing-induced myocardial ischemia were examined. Fourteen patients received perindoprilat and 11 patients received placebo. Based on LV function, 2 subgroups were formed in the perindoprilat group: 7 patients with LV dysfunction (LV ejection fraction <0.40), and 7 patients with normal LV function. After receiving the study medication, the pacing test was repeated. During the first pacing test both groups developed ischemia. After perindoprilat administration, the increase in systemic vascular resistance and LV end-diastolic pressure were significantly blunted (p <0.05). Further, the ischemia-induced increase in arterial and cardiac uptake of norepinephrine was inhibited by perindoprilat, and the increase in atrial natriuretic peptide was less pronounced; also, ST-segment depression was reduced by 32% compared with placebo (all p <0.05). In the group with LV dysfunction, perindoprilat reduced LV end-diastolic pressure significantly by 67% and myocardial lactate production was prevented, but this did not happen in the group with normal LV function. In addition, the increase in arterial norepinephrine was reduced by 74% and 33%, respectively (p <0.05). These results indicate that perindoprilat reduced acute, pacing-induced ischemia in normotensive patients. In patients with (asymptomatic) LV dysfunction these effects were more pronounced than in patients with normal LV function.