Carvedilol for prevention of restenosis after directional coronary atherectomy : final results of the European carvedilol atherectomy restenosis (EUROCARE) trial.

BACKGROUND: In addition to its known properties as a competitive, nonselective beta and alpha-1 receptor blocker, carvedilol directly inhibits vascular myocyte migration and proliferation and exerts antioxidant effects that are considerably greater than those of vitamin E or probucol. This provides the basis for an evaluation of carvedilol for the prevention of coronary restenosis. METHODS AND RESULTS: In a prospective, double-blind, randomized, placebo-controlled trial, 25 mg of carvedilol was given twice daily, starting 24 hours before scheduled directional coronary atherectomy and continuing for 5 months after a successful procedure. The primary end point was the minimal luminal diameter as determined during follow-up angiography 26+/-2 weeks after the procedure. Of 406 randomized patients, 377 underwent attempted atherectomy, and in 324 (88.9%), a

Comparison of safety and efficacy of carvedilol and metoprolol in stable angina pectoris.

In a double-blind, randomized, 3-month multicenter study, the safety and tolerability and the antianginal and anti-ischemic efficacy of carvedilol 25 to 50 mg twice daily were assessed in comparison with metoprolol 50 to 100 mg twice daily in younger and elderly patients with stable angina. After a 7-day placebo run-in at the end of which a symptom-limited bicycle ergometric exercise was performed, 368 patients were randomly allocated to the parallel treatment groups. After 4 weeks of therapy with a low dose, a further exercise test was performed and patients were titrated in single-blind fashion to the higher dose if the increase in total exercise time was < 1 minute, and there was no safety concern. After a further 8 weeks of treatment a third exercise test was performed. Carvedilol low dose/high dose was shown to be at least as safe and well tolerated as metoprolol low dose/high dose both in younger and elderly patients. There were no hitherto unknown adverse events and no marked change in the types of events after increase of the doses. Early adverse events after treatment initiation or uptitration were equal with both medications, indicating no particular risk associated with carvedilol's vasodilatory action. No rebound phenomena were observed. Both drugs showed good antianginal and anti-ischemic efficacy, with marked increases on uptitration including patients > or = 65 years of age. However, in the doses selected, which appeared equipotent with respect to beta blockade, carvedilol's improvement of time to 1-mm ST-segment depression was statistically significantly greater than that of metoprolol. This could be due to its additional vasodilatory or antioxidative actions. Based on the safety and efficacy data of the present study, use of the higher of the 2 recommended doses of carvedilol and metoprolol appears justified in younger and elderly patients without adequate therapeutic control at lower doses.

A double-blind comparison of the effects of carvedilol and captopril on serum lipid concentrations in patients with mild to moderate essential hypertension and dyslipidaemia.

We have studied 250 patients with mild to moderate essential hypertension (diastolic blood pressure 95-114 mmHg) and dyslipidaemia (high-density lipoprotein cholesterol (HDL-C) below 1.03 mmol.l-1, total cholesterol 5.17-9.05 mmol.l-1, and triglycerides 2.26-5.64 mmol.l-1) in a controlled double-blind, multicentre, parallel group trial. The patients took a fat-modified diet. After a 4-week placebo period, patients who continued to fulfil the selection criteria were randomly allocated to treatment with either carvedilol (a vasodilating beta-blocker) 25-50 mg o.d. (n = 116) or captopril (an ACE inhibitor) 25-50 mg o.d. (n = 117) for 6 months. In both groups there were favourable effects on the serum lipids. The relative changes (medians) in the carvedilol and captopril group were respectively: increase in HDL-C by 11% and 8%, decrease in total cholesterol by 11% and 10%, in low-density lipoprotein cholesterol by 16% and 12%, and in triglycerides by 13% and 14%. Equivalence of the two treatments was confirmed for the target variable change in HDL-C at a significance level of 5%. Reductions in supine systolic/diastolic blood pressures were comparable in the two groups (carvedilol: 23/19 mmHg, captopril: 20/18 mmHg). The improvement in lipid metabolism in patients treated with carvedilol is probably due to its alpha 1-blocking properties.

[Ovarian pseudocysts in female newborn infants: prenatal ultrasonic diagnosis and surgical consequences]. / Ovarialpseudozysten bei weiblichen Neugeborenen: Pränatale ultrasonographische Diagnose und chirurgische Konsequenz.

During the last year we diagnosed within the scope of preventive medical care of pregnant women in about the 30th pregnancy week, seven foetuses with abdominal cystic tumours by ultrasound examination. Postpartal ultrasound controls of the mature newborn confirmed the findings. After laparotomy we found ovarian pseudocysts with a volume up to 90 ccm. Histologically we could not identify ovarian tissue. In 66% of the cases we found small cysts on the contralateral ovary. Differential diagnosis and the possible complications must be considered. A laparotomy should be performed and only by high steroid serum level a conservative therapy with MPA should be considered. This is the case in premature newborn with an immature endocrine regulation mechanism.

Carvedilol versus verapamil in chronic stable angina: a multicentre trial.

OBJECTIVE: In a multicentre, double-blind, parallel group study, the anti-anginal and the anti-ischaemic efficacy of 12 weeks of therapy with the vasodilating beta-adrenoceptor-blocker carvedilol 25 mg b.i.d. was compared with verapamil 120 mg t.i.d. METHODS: During a 2-week placebo run-in period, patients were required to have two treadmill exercise tests (modified Bruce Protocol) differing by not more than 15% with regard to total exercise time (TET). Of 313 patients enrolled, 248 were randomized and 212 completed the study according to the protocol. RESULTS: The primary variable TET was analysed using the Cox Proportional Hazards Model to take into account censored values due to the patient stopping the exercise test for reasons other than angina. Forty-three per cent of patients allocated to carvedilol and 36% to verapamil did not stop with angina at the final visit. There was no difference in the TET between the groups, the risk ratio being 1.14 in favour of carvedilol (90% CI 0.85-1.52). TET increased from 378 s at baseline to 436 s at the final visit in the carvedilol group and from 386 to 438 s in the verapamil group. Results for time to angina and time to 1 mm ST-segment depression were similar. Compared to verapamil, carvedilol significantly reduced HR, systolic BP and rate pressure product at peak exercise. Analysis of 48 h Holter monitor data showed a greater reduction of HR and PVCs with carvedilol. Lown grading improved in both groups. Adverse events were reported by 48% (3.2% serious adverse events) of patients taking carvedilol and 58% (5.7% serious adverse events) taking verapamil. CONCLUSION: Carvedilol is at least as effective as verapamil in the management of chronic stable angina and demonstrated a favourable adverse event profile.