Carvedilol is a competitive antagonist of beta1, beta2 and alpha1 adrenoreceptors and, unlike other beta blockers, it is a powerful antioxidant, inhibiting cytotoxicity from oxygen radicals. In addition to its cardioprotective properties, carvedilol also has been found to have a mild beneficial effect on lipid levels in hypertensive patients with dyslipidemia. Van der Does and associates investigated the safety of higher dosages of carvedilol in patients with angina who did not adequately respond to lower dosages and compared the effects of carvedilol with those of metoprolol.
All 367 patients in the double-blind, randomized, multicenter study had exertional angina that improved with short-acting nitrates or rest. Coronary artery disease had been documented by angiography, a positive stress test or a previous myocardial infarction. Ergometric exercise testing was done before randomization and after each treatment period. Exercise test variables were symptom-limited total exercise time, time to onset of anginal pain and time to onset of 1-mm ST-segment depression.
Patients were initially randomized to receive 25 mg of carvedilol twice daily or 50 mg of metoprolol twice daily for four weeks. After four weeks of therapy at the low dosages, carvedilol and metoprolol dosages were increased if the total exercise time after the low-dose therapy was less than one minute. In this phase of the study, the carvedilol dosage was increased to 50 mg twice daily and the metoprolol dosage was increased to 100 mg twice daily. These dosages were continued for an additional eight weeks, after which ergometric exercise testing was again performed.
Both groups had a reduction in ST-segment depression of approximately 40 percent; reductions in heart rate and systolic blood pressure were also similar. Compared with metoprolol, carvedilol was found to improve the time to 1-mm ST-segment depression. The difference in this effect was statistically significant.
The occurrence of adverse events was similar between groups and ranged in severity from episodes of bradycardia, supraventricular tachycardia, dyspnea with sweating and wheezing, and atrial fibrillation, to less serious events such as dizziness, bronchitis, headache, back pain and gastroenteritis. Adverse events were more common among patients over 65 years of age.
The authors conclude that both treatment regimens produced clinically important improvements in exercise-induced angina. Carvedilol appeared to exert a somewhat greater anti-ischemic effect, as indicated by the variable time to 1-mm ST-segment depression. Since the response to the two drugs was equivalent with respect to beta blockade, it is thought that the vasodilatory and antioxidative effects of carvedilol may contribute to its beneficial influence on myocardial ischemia.