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 </=50% diameter stenosis was achieved without the use of a stent. Evaluable follow-up angiography was available in 292 eligible patients (90%). No differences in minimal luminal diameter (1.99+/-0.73 mm versus 2.00+/-0.74 mm), angiographic restenosis rate (23.4% versus 23.9%), target lesion revascularization (16.2 versus 14.5), or event-free survival (79.2% versus 79.7%) between the placebo and carvedilol groups were observed at 7 months. CONCLUSIONS: The maximum recommended daily dose of the antioxidant and beta-blocker carvedilol failed to reduce restenosis after successful atherectomy. These findings are in contrast to those of the Multivitamins and Probucol Trial, which raises doubts regarding the validity of the interpretation that restenosis reduction by probucol was via antioxidant effects. The relationship between antioxidant agents and restenosis remains to be elucidated.
RCT Entities:
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 </=50% diameter stenosis was achieved without the use of a stent. Evaluable follow-up angiography was available in 292 eligible patients (90%). No differences in minimal luminal diameter (1.99+/-0.73 mm versus 2.00+/-0.74 mm), angiographic restenosis rate (23.4% versus 23.9%), target lesion revascularization (16.2 versus 14.5), or event-free survival (79.2% versus 79.7%) between the placebo and carvedilol groups were observed at 7 months. CONCLUSIONS: The maximum recommended daily dose of the antioxidant and beta-blocker carvedilol failed to reduce restenosis after successful atherectomy. These findings are in contrast to those of the Multivitamins and Probucol Trial, which raises doubts regarding the validity of the interpretation that restenosis reduction by probucol was via antioxidant effects. The relationship between antioxidant agents and restenosis remains to be elucidated.
Authors: Stefanie A Fahlbusch; Dimitrios Tsikas; Christina Mehls; Frank-Mathias Gutzki; Rainer H Böger; Jürgen C Frölich; Dirk O Stichtenoth Journal: Eur J Clin Pharmacol Date: 2004-03-05 Impact factor: 2.953
Authors: Hermann Blessberger; Sharon R Lewis; Michael W Pritchard; Lizzy J Fawcett; Hans Domanovits; Oliver Schlager; Brigitte Wildner; Juergen Kammler; Clemens Steinwender Journal: Cochrane Database Syst Rev Date: 2019-09-23