Paclitaxel-Eluting Coronary Stents
http://www.100md.com
《新英格兰医药杂志》
To the Editor: The optimal duration of clopidogrel therapy after percutaneous coronary intervention is the subject of ongoing debate. Stone et al. (Jan. 15 issue)1 report the efficacy of paclitaxel-eluting stents as compared with bare-metal stents in reducing the rates of restenosis at nine months. Although clopidogrel therapy for six months was prescribed to prevent late thrombosis, the authors question the benefit of prolonged thienopyridine therapy in patients who have received a drug-eluting stent. Do the authors recommend a change in the duration of dual antiplatelet therapy for patients who have received these stents? As contemporary clinical practice suggests, drug-eluting stents are used for more complex lesions (i.e., bifurcation lesions), which are associated with higher rates of late thrombosis than are simple lesions.2
Clopidogrel therapy for at least 12 months is indicated for the prevention of late thrombosis after intracoronary radiation for in-stent restenosis.3 An additional benefit with 12 months of clopidogrel therapy has been demonstrated in patients undergoing elective percutaneous coronary intervention with a bare-metal stent.4 Furthermore, prolonged administration of clopidogrel in patients with acute coronary syndromes, many of whom will proceed to undergo coronary intervention, has established benefits.5 Clopidogrel therapy for six months may be insufficient in the era of drug-eluting stents.
Andrew E. Ajani, M.D.
Royal Melbourne Hospital
3050 Melbourne, Australia
Ron Waksman, M.D.
Washington Hospital Center
Washington, DC 20010
ron.waksman@medstar.net
References
Stone GW, Ellis SG, Cox DA, et al. A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease. N Engl J Med 2004;350:221-231.
Lemos PA, Serruys PW, van Domburg RT, et al. Unrestricted utilization of sirolimus-eluting stents compared with conventional bare stent implantation in the "real world": the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) Registry. Circulation 2004;109:190-195.
Waksman R, Ajani AE, Pinnow E, et al. Twelve versus six months of clopidogrel to reduce major cardiac events in patients undergoing gamma-radiation therapy for in-stent restenosis: Washington Radiation for In-Stent restenosis Trial (WRIST) 12 versus WRIST PLUS. Circulation 2002;106:776-778.
Steinhubl SR, Berger PB, Mann JT III, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 2002;288:2411-2420.
The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001;345:494-502.
The authors reply: Although studies in patients with acute coronary syndromes who undergo angioplasty suggest that the administration of thienopyridines should be continued for at least 9 to 12 months,1,2 prolonged therapy may be economically burdensome, and the risk of stent thrombosis should an interruption of thienopyridine therapy become necessary is unknown. In our study (TAXUS-IV), clopidogrel therapy for six months was empirically recommended to provide a wide margin of safety, although research in single-stent porcine models in vivo has shown equivalent rates of endothelialization with slow-release paclitaxel-eluting stents and bare-metal stents (Boston Scientific: unpublished data). It is unknown whether a shorter duration of thienopyridine therapy is sufficient for simple lesions or whether prolonged administration is required for complex lesions; this point will require formal testing.
Apart from providing protection against stent thrombosis, long-term administration of thienopyridine after angioplasty may promote freedom from future adverse cardiovascular events, either by preventing or mitigating plaque rupture or by decreasing the risk of spontaneous or device-induced thromboembolism. In this regard, the encouraging results of the CREDO (Clopidogrel for the Reduction of Events during Observation) trial require replication, since the administration of clopidogrel before stenting contributed to the late benefits seen with long-term use of clopidogrel.2 In the absence of evidence that thienopyridine administration for more than 1 year has an acceptable cost–benefit ratio and is cost effective, we recommend 6 to 12 months of clopidogrel after implantation of a drug-eluting stent.
Gregg W. Stone, M.D.
Cardiovascular Research Foundation
New York, NY 10022
gstone@crf.org
Stephen G. Ellis, M.D.
Cleveland Clinic Foundation
Cleveland, OH 44195
Mary E. Russell, M.D.
Boston Scientific
Natick, MA 01760
References
The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001;345:494-502.
Steinhubl SR, Berger PB, Mann JT III, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 2002;288:2411-2420.
Clopidogrel therapy for at least 12 months is indicated for the prevention of late thrombosis after intracoronary radiation for in-stent restenosis.3 An additional benefit with 12 months of clopidogrel therapy has been demonstrated in patients undergoing elective percutaneous coronary intervention with a bare-metal stent.4 Furthermore, prolonged administration of clopidogrel in patients with acute coronary syndromes, many of whom will proceed to undergo coronary intervention, has established benefits.5 Clopidogrel therapy for six months may be insufficient in the era of drug-eluting stents.
Andrew E. Ajani, M.D.
Royal Melbourne Hospital
3050 Melbourne, Australia
Ron Waksman, M.D.
Washington Hospital Center
Washington, DC 20010
ron.waksman@medstar.net
References
Stone GW, Ellis SG, Cox DA, et al. A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease. N Engl J Med 2004;350:221-231.
Lemos PA, Serruys PW, van Domburg RT, et al. Unrestricted utilization of sirolimus-eluting stents compared with conventional bare stent implantation in the "real world": the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) Registry. Circulation 2004;109:190-195.
Waksman R, Ajani AE, Pinnow E, et al. Twelve versus six months of clopidogrel to reduce major cardiac events in patients undergoing gamma-radiation therapy for in-stent restenosis: Washington Radiation for In-Stent restenosis Trial (WRIST) 12 versus WRIST PLUS. Circulation 2002;106:776-778.
Steinhubl SR, Berger PB, Mann JT III, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 2002;288:2411-2420.
The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001;345:494-502.
The authors reply: Although studies in patients with acute coronary syndromes who undergo angioplasty suggest that the administration of thienopyridines should be continued for at least 9 to 12 months,1,2 prolonged therapy may be economically burdensome, and the risk of stent thrombosis should an interruption of thienopyridine therapy become necessary is unknown. In our study (TAXUS-IV), clopidogrel therapy for six months was empirically recommended to provide a wide margin of safety, although research in single-stent porcine models in vivo has shown equivalent rates of endothelialization with slow-release paclitaxel-eluting stents and bare-metal stents (Boston Scientific: unpublished data). It is unknown whether a shorter duration of thienopyridine therapy is sufficient for simple lesions or whether prolonged administration is required for complex lesions; this point will require formal testing.
Apart from providing protection against stent thrombosis, long-term administration of thienopyridine after angioplasty may promote freedom from future adverse cardiovascular events, either by preventing or mitigating plaque rupture or by decreasing the risk of spontaneous or device-induced thromboembolism. In this regard, the encouraging results of the CREDO (Clopidogrel for the Reduction of Events during Observation) trial require replication, since the administration of clopidogrel before stenting contributed to the late benefits seen with long-term use of clopidogrel.2 In the absence of evidence that thienopyridine administration for more than 1 year has an acceptable cost–benefit ratio and is cost effective, we recommend 6 to 12 months of clopidogrel after implantation of a drug-eluting stent.
Gregg W. Stone, M.D.
Cardiovascular Research Foundation
New York, NY 10022
gstone@crf.org
Stephen G. Ellis, M.D.
Cleveland Clinic Foundation
Cleveland, OH 44195
Mary E. Russell, M.D.
Boston Scientific
Natick, MA 01760
References
The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001;345:494-502.
Steinhubl SR, Berger PB, Mann JT III, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 2002;288:2411-2420.