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Carvedilol improves endothelium-dependent dilatation in patients with coronary artery disease
Y Matsuda1, H Akita, M Terashima
1First Department of Internal Medicine, Kobe University School of Medicine, Kobe, Japan.
Insights
Long-term carvedilol treatment improved endothelial function in patients with coronary artery disease (CAD) by reducing oxidative stress. This suggests carvedilol
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Oxidative Stress Research
Background:
- Endothelial dysfunction, characterized by impaired flow-mediated dilatation (FMD), is prevalent in coronary artery disease (CAD) and linked to increased oxidative stress.
- Carvedilol, a beta-blocker with known in vitro antioxidant properties, has not been clinically evaluated for its effects on endothelial dysfunction in CAD patients.
Purpose of the Study:
- To investigate the clinical efficacy of carvedilol in improving endothelial function in patients with established coronary atherosclerosis.
- To assess whether carvedilol's effects on endothelial function are related to its antioxidant activity.
Main Methods:
- A randomized, placebo-controlled study involving 29 CAD patients (17 with myocardial infarction, 12 with angina) and 13 healthy controls.
- Brachial artery flow-mediated dilatation (FMD) and nitroglycerin-induced dilatation were measured using high-resolution ultrasound before and after short-term (2 hours) and long-term (4 months) treatment with carvedilol or placebo.
- Plasma levels of thiobarbituric acid-reactive substances (TBARS) were measured as an indicator of oxidative stress.
Main Results:
- Patients with CAD exhibited significantly lower FMD compared to controls, while nitroglycerin-induced dilatation was comparable.
- Long-term carvedilol treatment significantly improved FMD (from 5.1% to 7.8%, P <.01) but short-term treatment did not.
- Carvedilol significantly reduced plasma TBARS levels after long-term treatment, indicating a decrease in oxidative stress, whereas placebo had no significant effect on FMD or TBARS.
Conclusions:
- Long-term administration of carvedilol effectively improves endothelial function in patients with coronary artery disease.
- The observed improvement in endothelial function is likely attributable to carvedilol's antioxidant properties, which reduce systemic oxidative stress.
Objective:
Flow-mediated, endothelium-dependent dilatation (FMD) of the coronary and peripheral circulation is impaired by increased oxidative stress in patients with coronary artery disease (CAD). Carvedilol is a novel beta-blocker that also shows an antioxidant effect in vitro. However, the effect of carvedilol on endothelial dysfunction associated with established coronary atherosclerosis has not been examined in the clinical setting.
Methods:
We studied 29 patients with CAD, including 17 with recent myocardial infarction and 12 with stable effort angina pectoris. Nineteen patients received carvedilol (10 with infarction and 9 with angina), and 10 were treated with placebo (7 with infarction and 3 with angina). We also studied 13 age- and sex-matched control subjects. Brachial FMD during reactive hyperemia and nitroglycerin-induced, endothelium-independent dilatation were assessed by high-resolution ultrasound.
Results:
FMD was smaller in patients with CAD compared with controls, although nitroglycerin-induced dilatation was similar. Carvedilol significantly improved FMD after long-term treatment (5. 1% +/- 0.4% at baseline to 7.8% +/- 0.3% after 4 months; P <.01) but not after short-term treatment (5.1% +/- 0.4% at baseline to 5.0% +/- 0.7% after 2 hours). Placebo therapy had no effect on endothelial dysfunction. Neither carvedilol nor placebo had an effect on nitroglycerin-induced dilatation after short- and long-term treatment. Long-term carvedilol therapy also significantly decreased the plasma level of thiobarbituric acid-reactive substances compared with placebo (carvedilol, 5.8 +/- 0.4 nmol/mL to 4.6 +/- 0.3 nmol/mL, P <.01; placebo, 5.9 +/- 0.4 nmol/mL to 5.8 +/- 0.4 nmol/mL, P = not significant).
Conclusion:
These findings suggest that the improvement of endothelial function by carvedilol may be caused by its antioxidant activity.