关于Drug-Eluting Coronary Stents的原因,关于Drug-Eluting Coronary Stents的相关知识。 To the Editor: The article by Dibra et al. (Aug. 18 issue)1 advances our understanding of the differences between paclitaxel-eluting stents and sirolimus-eluting stents when used to prevent restenosis in patients with diabetes. However, in this study, the rate of in-segment restenosis was 16.5 percent in the paclitaxel-stent group and only 6.9 percent in the sirolimus-stent group (P=0.03) at nine months after intervention, and revascularization was performed in lesions that were complex (type B2 or C) in a high percentage: 74 percent in the paclitaxel-stent group, and 82 percent in the sirolimus-stent group. This is very different from the results of other studies in patients with diabetes, such as the SIRIUS (Sirolimus-Eluting Balloon-Expandable Stent in the Treatment of Patients with de Novo Native Coronary-Artery Lesions) trial,2 in which the rate of in-segment restenosis in the sirolimus-stent group was higher than that in the sirolimus-stent group in the study by Dibra et al. (18 percent vs. 6.9 percent at nine months) despite fewer complex lesions (59 percent vs. 82 percent) and without the inclusion of a target lesion in an ostium, a bifurcation, or an "unprotected" left main coronary artery or treatment of nontarget lesions in the same or a different coronary vessel during the index procedure. Do the authors have an explanation for this difference?
Jose A. Alarcón, M.D.
Juan M. Arribas, M.D.
Valeriano Ruiz, M.D.
Hospital Santiago Apostol
01080 Vitoria, Spain
josalar13@yahoo.es
References
Dibra A, Kastrati A, Mehilli J, et al. Paclitaxel-eluting or sirolimus-eluting stents to prevent restenosis in diabetic patients. N Engl J Med 2005;353:663-670.
Moussa I, Leon MB, Baim DS, et al. Impact of sirolimus-eluting stents on outcome in diabetic patients: a SIRIUS (SIRolImUS-coated Bx Velocity balloon-expandable stent in the treatment of patients with the de novo coronary artery lesions) substudy. Circulation 2004;109:2273-2278.
To the Editor: Dibra et al. reported more effective prevention of restenosis with the use of sirolimus-eluting stents than with paclitaxel-eluting stents in patients with diabetes. However, their findings may have resulted from factors not related to the antiproliferative agents used in the stents studied. Selective angiotensin II type 1–receptor blockers (ARBs) have been shown to prevent restenosis after stent implantation1; statins — used alone or in combination with ARBs — exert a similar effect.2 Surprisingly, the authors did not provide any data, particularly at the end of the follow-up period, regarding the use of these drugs, although 70 to 80 percent of the patients presented with hypertension, hypercholesterolemia, or both. Moreover, since diabetes is a progressive disease, blood glucose control and diabetes treatment may have changed during follow-up and thus influenced the course of coronary atherosclerosis,3 but again no data were given. Because glycemic control and vascular drugs affect endothelial function and structure, excluding these potential confounding factors raises doubts about the investigators' conclusion that sirolimus-eluting stents are superior in patients with diabetes.
Leszek Czupryniak, M.D., Ph.D.
Maciej Pawlowski, M.D.
Jerzy Loba, M.D., Ph.D.
Medical University of Lodz
90-153 Lodz, Poland
bigosik@poczta.onet.pl
References
Peters S, Trummel M, Meyners W, Koehler B, Westermann K. Valsartan versus ACE inhibition after bare metal stent implantation -- results of the VALVACE trial. Int J Cardiol 2005;98:331-335.
Nishikawa H, Miura S, Shimomura H, et al. Combined treatment with statin and angiotensin-receptor blocker after stenting as a useful strategy for prevention of coronary restenosis. J Cardiol 2005;45:107-113.
U. K. Prospective Diabetes Study Group. U.K. prospective diabetes study 16 -- overview of 6 years' therapy of type II diabetes: a progressive disease. Diabetes 1995;44:1249-1258.
To the Editor: Windecker et al. (Aug. 18 issue)1 reported the results of a randomized clinical trial called SIRTAX (Sirolimus-Eluting Stent Compared with Paclitaxel-Eluting Stent for Coronary Revascularization). Despite a late luminal loss within the stent of about 0.3 mm in the paclitaxel-stent group, similar to that observed in the TAXUS-IV trial,2 the incidence of target-lesion revascularization was significantly higher in the trial by Windecker et al. (8.3 percent, vs. 3.0 percent in the TAXUS-IV trial). We are wondering whether this difference may be attributed to very liberal performance of target-lesion revascularization in the SIRTAX trial, possibly as a result of different protocol requirements.
In cases of angiographically moderate restenosis, proven ischemia was required by the TAXUS-IV protocol to proceed to target-lesion revascularization, whereas symptoms were considered sufficient reason in the study by Windecker et al.1,2 Therefore, it would be helpful if Windecker et al. could provide details concerning the rate of target-lesion revascularization performed in patients who, at entry into the study, gave consent for follow-up angiography as compared with the rate in those who gave consent for only clinical follow-up.
Robert F. Bonvini, M.D.
Vitali Verin, M.D.
University Hospital of Geneva
1211 Geneva, Switzerland
robert.bonvini@hcuge.ch
References
Windecker S, Remondino A, Eberli FR, et al. Sirolimus-eluting and paclitaxel-eluting stents for coronary revascularization. N Engl J Med 2005;353:653-662.
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.
To the Editor: The comparative trials of sirolimus-eluting and paclitaxel-eluting stents, accompanied by an editorial,1 led to the conclusion that sirolimus-eluting stents "provide an angiographic and clinical edge" over paclitaxel-eluting stents. This assumption, driven by single-center trials with nonblinded randomization, may be incorrect and misleading. It contradicts the results of the REALITY (Prospective Randomized Multi-center Head-to-Head Comparison of the Sirolimus-Eluting Stent and the Paclitaxel-Eluting Stent ) trial,2 which failed to detect differences in restenosis or any clinical events and in whose group with diabetes paclitaxel was favored with respect to in-lesion restenosis.
In the SIRTAX trial, baseline characteristics of the patients were similar to those of patients enrolled in the SIRIUS3 and the TAXUS-IV4 trials. Although the results in the sirolimus-stent group in the SIRTAX trial are similar to those in the SIRIUS trial, the restenosis and revascularization rates in the paclitaxel-stent group of the SIRTAX trial are higher than those in the TAXUS-IV trial. It is hard to imagine that the biology is changing across continents. We believe that the conclusion of stent superiority should be driven only by trials that are blinded, randomized, and adequately powered (>80 percent) with clinically relevant end points in order to avert unnecessary confusion for patients and cardiologists.
Ron Waksman, M.D.
Roswitha M. Wolfram, M.D.
Washington Hospital Center
Washington, DC 20010
ron.waksman@medstar.net
References
Moliterno DJ. Healing Achilles -- sirolimus versus paclitaxel. N Engl J Med 2005;353:724-727.
Morice M-C, Serruys PW, Colombo A, et al. Eight-month outcome of the REALITY Study: a prospective, randomized, multi-center head-to-head comparison of the sirolimus-eluting stent (Cypher) and the paclitaxel-eluting stent (Taxus). Presented at the 2005 Annual Scientific Session of the American College of Cardiology, Orlando, Fla., March 6–9, 2005.
Moses JW, Leon MB, Popma JJ, et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 2003;349:1315-1323.
Stone GW, Ellis SG, Cox DA, et al. One-year clinical results with the slow-release, polymer-based, paclitaxel-eluting TAXUS stent: the TAXUS-IV trial. Circulation 2004;109:1942-1947.
To the Editor: After reviewing the results of the SIRTAX trial, by Windecker et al., and the Intracoronary Stenting and Angiographic Results: Do Diabetic Patients Derive Similar Benefit from Paclitaxel-Eluting and Sirolimus-Eluting Stents (ISAR-DIABETES) trial, by Dibra et al., we disagree with the comment of Moliterno, the editorialist, that sirolimus stents "provide an angiographic and clinical edge over . . . paclitaxel-eluting stents." A 44 percent reduction in the relative risk of target-lesion revascularization is not merely an "edge," particularly given the high event rate in question (1.2 million coronary interventions annually1).
Moliterno also states that the benefits were driven by soft outcomes, although coronary interventions are usually undertaken to improve angina and the quality of life. It would be unreasonable to expect differences in hard outcomes without much larger or longer trials. We also disagree that a "paclitaxel-eluting stent holds an edge on . . . deliverability . . . ," since successful implantation was achieved equally (99 percent) with both stents. Although it is true that the differences in outcome may be attributed to any of the three components of the drug-eluting stents, it is fair to conclude that the currently available sirolimus stents do not simply provide a clinical edge over their paclitaxel counterparts but, rather, represent a superior treatment strategy.
Hani Jneid, M.D.
Ik-Kyung Jang, M.D.
Igor Palacios, M.D.
Massachusetts General Hospital
Boston, MA 02114
jneid.hani@mgh.harvard.edu
Dr. Jang reports having received a research grant and consulting fees from Boston Scientific and honoraria from Cordis and Johnson & Johnson.
References
American Heart Association. Heart disease and stroke statistics — 2005 update. (Accessed November 1, 2005, at http://americanheart.org/presenter.jhtml?identifier=3000090.)
Dr. Dibra and colleagues reply: Dr. Alarcón and colleagues point out the difference in angiographic-restenosis rates between patients in the sirolimus-stent group of our study and the subgroup of patients with diabetes in the sirolimus-stent group in the SIRIUS trial.1 However, results of subgroup analyses are not always reliable. Indeed, subgroup analyses of diabetic patients treated with sirolimus-eluting stents showed a restenosis rate of 17.6 percent in the SIRIUS trial1 and no restenosis at all in the RAVEL (Randomized Study with the Sirolimus-Coated Bx Velocity Balloon-Expandable Stent in the Treatment of Patients with de Novo Native Coronary Artery Lesions) trial.2 Only two randomized studies have specifically evaluated the use of sirolimus-eluting stents in diabetic patients; the restenosis rates were 7.7 percent in the DIABETES (Diabetes and Sirolimus-Eluting Stent) study3 and 6.9 percent in our ISAR-DIABETES study.
Dr. Czupryniak and colleagues are concerned about a potential bias introduced in the restenosis analysis by possible differences in glycemic control and in the use of selective ARBs and statins between the two groups in our study. Although there is insufficient evidence to support an influence of these factors on restenosis, we expanded our analysis to address these issues. There were no significant differences in either glycemic control or concomitant therapy between the two study groups. At the time of follow-up angiography, the mean (±SD) level of glycosylated hemoglobin was 7.3±1.1 percent among patients in the paclitaxel-stent group and 7.1±1.1 percent among patients in the sirolimus-stent group (P=0.28). After discharge, 5.6 percent of the patients in the paclitaxel-stent group and 4.0 percent in the sirolimus-stent group received ARBs (P=0.72); 85.6 percent of the patients in the paclitaxel-stent group and 84.8 percent in the sirolimus-stent group received statins (P=0.86); 88.8 percent of the patients in the paclitaxel-stent group and 88.0 percent of the patients in the sirolimus-stent group received angiotensin-converting–enzyme inhibitors (P=0.84); and 96.8 percent of the patients in the paclitaxel-stent group and 94.4 percent of the patients in the sirolimus-stent group received beta-blockers (P=0.35).
Adnan Kastrati, M.D.
Alban Dibra, M.D.
Albert Sch?mig, M.D.
Deutsches Herzzentrum
80636 Munich, Germany
Since publication of the article, Dr. Kastrati reports having received lecture fees from Bristol-Myers Squibb, Cordis, Lilly, and Medtronic.
References
Moussa I, Leon MB, Baim DS, et al. Impact of sirolimus-eluting stents on outcome in diabetic patients: a SIRIUS (SIRolImUS-coated Bx Velocity balloon-expandable stent in the treatment of patients with de novo coronary artery lesions) substudy. Circulation 2004;109:2273-2278.
Abizaid A, Costa MA, Blanchard D, et al. Sirolimus-eluting stents inhibit neointimal hyperplasia in diabetic patients: insights from the RAVEL Trial. Eur Heart J 2004;25:107-112.
DIABETes and sirolimus-Eluting Stent trial: the DIABETES Trial. (Accessed November 1, 2005, at http://www.tctmd.com/csportal/ShowBinary/BEA%20Repository/TCTMD%20Portal/EPSlidePresPool/ExpertPresentation_1111877875569//pdfFile.)
Dr. Windecker and colleagues reply: Drs. Bonvini and Verin correctly outline differences in the definition of target-lesion revascularization between the SIRTAX and TAXUS-IV trials.1 However, SIRTAX was a multilesion trial, and therefore the rate of target-lesion revascularization, reported per patient, should be higher than in a single-lesion study such as TAXUS-IV. The rate of target-lesion revascularization per lesion in SIRTAX was 3.5 percent for the sirolimus group and 5.9 percent for the paclitaxel group. The following considerations further substantiate our findings. First, the SIRTAX definition of target-lesion revascularization is common to many coronary-stent trials,2 including SIRIUS, and reflects clinical practice to intervene in symptomatic patients with stenoses of 50 percent or more. Second, severe late loss (1.2 mm) occurred more frequently with paclitaxel than with sirolimus stents (10.7 percent vs. 5.8 percent, P=0.02). Third, differences in rates of target-lesion revascularization persisted after a post hoc analysis disregarding revascularization driven exclusively by angiography (4.4 percent in the sirolimus-stent group vs. 7.1 percent in the paclitaxel-stent group, P=0.07). Fourth, rates of target-vessel failure at six months (4.2 percent in the sirolimus-stent group vs. 7.1 percent in the paclitaxel-stent group, P=0.05) were different before follow-up angiography and similar to those in BASKET (Basel Stent Cost-Effectiveness Trial),3 another trial comparing sirolimus and paclitaxel stents in a real-world setting (5.7 percent vs. 8.5 percent, P not significant). Fifth, a meta-analysis of six randomized trials comparing sirolimus and paclitaxel stents4 showed rates of target-lesion revascularization (5.1 percent in the sirolimus-stent group vs. 7.8 percent in the paclitaxel-stent group, P=0.001) that were similar to those in SIRTAX.
Stephan Windecker, M.D.
Peter Jüni, M.D.
Bernhard Meier, M.D.
University Hospital Bern
3010 Bern, Switzerland
stephan.windecker@insel.ch
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.
Cutlip DE, Chauhan MS, Baim DS, et al. Clinical restenosis after coronary stenting: perspectives from multicenter clinical trials. J Am Coll Cardiol 2002;40:2082-2089.
Kaiser C, Brunner-La Rocca HP, Buser PT, et al. Incremental cost-effectiveness of drug-eluting stents compared with a third-generation bare-metal stent in a real-world setting: randomised Basel Stent Kosten Effektivitats Trial (BASKET). Lancet 2005;366:921-929.
Kastrati A, Dibra A, Eberle S, et al. Sirolimus-eluting stents vs paclitaxel-eluting stents in patients with coronary artery disease: meta-analysis of randomized trials. JAMA 2005;294:819-825.
Dr. Moliterno replies: The sharply contrasting views of respected leaders, as illustrated by the letters of Drs. Waksman and Wolfram and Dr. Jneid et al., demonstrate the need for large-scale trials in the era of drug-eluting stents. My interpretation of SIRTAX and ISAR-DIABETES is supported by a separate meta-analysis.1 This study included all randomized head-to-head trials of drug-eluting stents and 3669 patients (5 percent from a single-center trial, 58 percent from two-center trials, and 37 percent from a multicenter trial). The odds ratio for target-vessel revascularization was 0.64 (95 percent confidence interval, 0.49 to 0.84) favoring the sirolimus-eluting stent. Although the largest study, REALITY,2 found no difference between the stents, it did have low rates of late luminal loss and revascularization. The odds ratio for target-vessel revascularization in the REALITY trial was 0.92 (95 percent confidence interval, 0.57 to 1.49), favoring the sirolimus-eluting stent, and fits within the confidence intervals of all the previous trials, suggesting that it is in fact consistent with them.
With respect to the comments of Jneid et al.: the overall odds ratio for target-vessel revascularization of 0.64 translates into a 34 percent reduction in risk with sirolimus-eluting stents, which is comparable to the reduction in restenosis provided by bare-metal stents as compared with balloon angioplasty. As noted by Drs. Waksman and Wolfram, the data driving this difference in target-vessel revascularization are from a limited number of study centers. So, if we choose to look most skeptically at these results and consider only the upper confidence limit, the relative risk reduction could be as low as 14 percent and the absolute risk reduction would be as low as 1.1 percent. This weakest-effect scenario means that approximately 90 patients would need to be treated with a sirolimus-eluting stent, rather than a paclitaxel-eluting stent, to prevent one additional target-vessel revascularization. Yet, among patient groups with higher rates of average late luminal loss and clinical restenosis, the benefit of sirolimus-eluting stents appears more distinct.
Jneid et al. disagree with my notion that the Taxus stent has an edge in deliverability. Admittedly, I based this view on my personal experience and that of many colleagues. I do not agree that the similar rates of successful stent implantation from a selected cohort indicate similar deliverability. We would have to presume that the guide support, wire stiffness, extent of predilation, and procedural fluoroscopic times were the same in order for these two stents to be deemed similar in this regard.
David J. Moliterno, M.D.
University of Kentucky
Lexington, KY 40536
moliterno@uky.edu
References
Kastrati A, Dibra A, Eberle S, et al. Sirolimus-eluting stents vs paclitaxel-eluting stents in patients with coronary artery disease: meta-analysis of randomized trials. JAMA 2005;294:819-825.
Morice M-C, Serruys PW, Colombo A, et al. Eight-month outcome of the REALITY Study: a prospective, randomized, multi-center head-to-head comparison of the sirolimus-eluting stent (Cypher) and the paclitaxel-eluting stent (Taxus). Presented at the 2005 Annual Scientific Session of the American College of Cardiology, Orlando, Fla., March 6–9, 2005. (文章出处：《新英格兰医药杂志》)
Jose A. Alarcón, M.D.
Juan M. Arribas, M.D.
Valeriano Ruiz, M.D.
Hospital Santiago Apostol
01080 Vitoria, Spain
josalar13@yahoo.es
References
Dibra A, Kastrati A, Mehilli J, et al. Paclitaxel-eluting or sirolimus-eluting stents to prevent restenosis in diabetic patients. N Engl J Med 2005;353:663-670.
Moussa I, Leon MB, Baim DS, et al. Impact of sirolimus-eluting stents on outcome in diabetic patients: a SIRIUS (SIRolImUS-coated Bx Velocity balloon-expandable stent in the treatment of patients with the de novo coronary artery lesions) substudy. Circulation 2004;109:2273-2278.
To the Editor: Dibra et al. reported more effective prevention of restenosis with the use of sirolimus-eluting stents than with paclitaxel-eluting stents in patients with diabetes. However, their findings may have resulted from factors not related to the antiproliferative agents used in the stents studied. Selective angiotensin II type 1–receptor blockers (ARBs) have been shown to prevent restenosis after stent implantation1; statins — used alone or in combination with ARBs — exert a similar effect.2 Surprisingly, the authors did not provide any data, particularly at the end of the follow-up period, regarding the use of these drugs, although 70 to 80 percent of the patients presented with hypertension, hypercholesterolemia, or both. Moreover, since diabetes is a progressive disease, blood glucose control and diabetes treatment may have changed during follow-up and thus influenced the course of coronary atherosclerosis,3 but again no data were given. Because glycemic control and vascular drugs affect endothelial function and structure, excluding these potential confounding factors raises doubts about the investigators' conclusion that sirolimus-eluting stents are superior in patients with diabetes.
Leszek Czupryniak, M.D., Ph.D.
Maciej Pawlowski, M.D.
Jerzy Loba, M.D., Ph.D.
Medical University of Lodz
90-153 Lodz, Poland
bigosik@poczta.onet.pl
References
Peters S, Trummel M, Meyners W, Koehler B, Westermann K. Valsartan versus ACE inhibition after bare metal stent implantation -- results of the VALVACE trial. Int J Cardiol 2005;98:331-335.
Nishikawa H, Miura S, Shimomura H, et al. Combined treatment with statin and angiotensin-receptor blocker after stenting as a useful strategy for prevention of coronary restenosis. J Cardiol 2005;45:107-113.
U. K. Prospective Diabetes Study Group. U.K. prospective diabetes study 16 -- overview of 6 years' therapy of type II diabetes: a progressive disease. Diabetes 1995;44:1249-1258.
To the Editor: Windecker et al. (Aug. 18 issue)1 reported the results of a randomized clinical trial called SIRTAX (Sirolimus-Eluting Stent Compared with Paclitaxel-Eluting Stent for Coronary Revascularization). Despite a late luminal loss within the stent of about 0.3 mm in the paclitaxel-stent group, similar to that observed in the TAXUS-IV trial,2 the incidence of target-lesion revascularization was significantly higher in the trial by Windecker et al. (8.3 percent, vs. 3.0 percent in the TAXUS-IV trial). We are wondering whether this difference may be attributed to very liberal performance of target-lesion revascularization in the SIRTAX trial, possibly as a result of different protocol requirements.
In cases of angiographically moderate restenosis, proven ischemia was required by the TAXUS-IV protocol to proceed to target-lesion revascularization, whereas symptoms were considered sufficient reason in the study by Windecker et al.1,2 Therefore, it would be helpful if Windecker et al. could provide details concerning the rate of target-lesion revascularization performed in patients who, at entry into the study, gave consent for follow-up angiography as compared with the rate in those who gave consent for only clinical follow-up.
Robert F. Bonvini, M.D.
Vitali Verin, M.D.
University Hospital of Geneva
1211 Geneva, Switzerland
robert.bonvini@hcuge.ch
References
Windecker S, Remondino A, Eberli FR, et al. Sirolimus-eluting and paclitaxel-eluting stents for coronary revascularization. N Engl J Med 2005;353:653-662.
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.
To the Editor: The comparative trials of sirolimus-eluting and paclitaxel-eluting stents, accompanied by an editorial,1 led to the conclusion that sirolimus-eluting stents "provide an angiographic and clinical edge" over paclitaxel-eluting stents. This assumption, driven by single-center trials with nonblinded randomization, may be incorrect and misleading. It contradicts the results of the REALITY (Prospective Randomized Multi-center Head-to-Head Comparison of the Sirolimus-Eluting Stent and the Paclitaxel-Eluting Stent ) trial,2 which failed to detect differences in restenosis or any clinical events and in whose group with diabetes paclitaxel was favored with respect to in-lesion restenosis.
In the SIRTAX trial, baseline characteristics of the patients were similar to those of patients enrolled in the SIRIUS3 and the TAXUS-IV4 trials. Although the results in the sirolimus-stent group in the SIRTAX trial are similar to those in the SIRIUS trial, the restenosis and revascularization rates in the paclitaxel-stent group of the SIRTAX trial are higher than those in the TAXUS-IV trial. It is hard to imagine that the biology is changing across continents. We believe that the conclusion of stent superiority should be driven only by trials that are blinded, randomized, and adequately powered (>80 percent) with clinically relevant end points in order to avert unnecessary confusion for patients and cardiologists.
Ron Waksman, M.D.
Roswitha M. Wolfram, M.D.
Washington Hospital Center
Washington, DC 20010
ron.waksman@medstar.net
References
Moliterno DJ. Healing Achilles -- sirolimus versus paclitaxel. N Engl J Med 2005;353:724-727.
Morice M-C, Serruys PW, Colombo A, et al. Eight-month outcome of the REALITY Study: a prospective, randomized, multi-center head-to-head comparison of the sirolimus-eluting stent (Cypher) and the paclitaxel-eluting stent (Taxus). Presented at the 2005 Annual Scientific Session of the American College of Cardiology, Orlando, Fla., March 6–9, 2005.
Moses JW, Leon MB, Popma JJ, et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 2003;349:1315-1323.
Stone GW, Ellis SG, Cox DA, et al. One-year clinical results with the slow-release, polymer-based, paclitaxel-eluting TAXUS stent: the TAXUS-IV trial. Circulation 2004;109:1942-1947.
To the Editor: After reviewing the results of the SIRTAX trial, by Windecker et al., and the Intracoronary Stenting and Angiographic Results: Do Diabetic Patients Derive Similar Benefit from Paclitaxel-Eluting and Sirolimus-Eluting Stents (ISAR-DIABETES) trial, by Dibra et al., we disagree with the comment of Moliterno, the editorialist, that sirolimus stents "provide an angiographic and clinical edge over . . . paclitaxel-eluting stents." A 44 percent reduction in the relative risk of target-lesion revascularization is not merely an "edge," particularly given the high event rate in question (1.2 million coronary interventions annually1).
Moliterno also states that the benefits were driven by soft outcomes, although coronary interventions are usually undertaken to improve angina and the quality of life. It would be unreasonable to expect differences in hard outcomes without much larger or longer trials. We also disagree that a "paclitaxel-eluting stent holds an edge on . . . deliverability . . . ," since successful implantation was achieved equally (99 percent) with both stents. Although it is true that the differences in outcome may be attributed to any of the three components of the drug-eluting stents, it is fair to conclude that the currently available sirolimus stents do not simply provide a clinical edge over their paclitaxel counterparts but, rather, represent a superior treatment strategy.
Hani Jneid, M.D.
Ik-Kyung Jang, M.D.
Igor Palacios, M.D.
Massachusetts General Hospital
Boston, MA 02114
jneid.hani@mgh.harvard.edu
Dr. Jang reports having received a research grant and consulting fees from Boston Scientific and honoraria from Cordis and Johnson & Johnson.
References
American Heart Association. Heart disease and stroke statistics — 2005 update. (Accessed November 1, 2005, at http://americanheart.org/presenter.jhtml?identifier=3000090.)
Dr. Dibra and colleagues reply: Dr. Alarcón and colleagues point out the difference in angiographic-restenosis rates between patients in the sirolimus-stent group of our study and the subgroup of patients with diabetes in the sirolimus-stent group in the SIRIUS trial.1 However, results of subgroup analyses are not always reliable. Indeed, subgroup analyses of diabetic patients treated with sirolimus-eluting stents showed a restenosis rate of 17.6 percent in the SIRIUS trial1 and no restenosis at all in the RAVEL (Randomized Study with the Sirolimus-Coated Bx Velocity Balloon-Expandable Stent in the Treatment of Patients with de Novo Native Coronary Artery Lesions) trial.2 Only two randomized studies have specifically evaluated the use of sirolimus-eluting stents in diabetic patients; the restenosis rates were 7.7 percent in the DIABETES (Diabetes and Sirolimus-Eluting Stent) study3 and 6.9 percent in our ISAR-DIABETES study.
Dr. Czupryniak and colleagues are concerned about a potential bias introduced in the restenosis analysis by possible differences in glycemic control and in the use of selective ARBs and statins between the two groups in our study. Although there is insufficient evidence to support an influence of these factors on restenosis, we expanded our analysis to address these issues. There were no significant differences in either glycemic control or concomitant therapy between the two study groups. At the time of follow-up angiography, the mean (±SD) level of glycosylated hemoglobin was 7.3±1.1 percent among patients in the paclitaxel-stent group and 7.1±1.1 percent among patients in the sirolimus-stent group (P=0.28). After discharge, 5.6 percent of the patients in the paclitaxel-stent group and 4.0 percent in the sirolimus-stent group received ARBs (P=0.72); 85.6 percent of the patients in the paclitaxel-stent group and 84.8 percent in the sirolimus-stent group received statins (P=0.86); 88.8 percent of the patients in the paclitaxel-stent group and 88.0 percent of the patients in the sirolimus-stent group received angiotensin-converting–enzyme inhibitors (P=0.84); and 96.8 percent of the patients in the paclitaxel-stent group and 94.4 percent of the patients in the sirolimus-stent group received beta-blockers (P=0.35).
Adnan Kastrati, M.D.
Alban Dibra, M.D.
Albert Sch?mig, M.D.
Deutsches Herzzentrum
80636 Munich, Germany
Since publication of the article, Dr. Kastrati reports having received lecture fees from Bristol-Myers Squibb, Cordis, Lilly, and Medtronic.
References
Moussa I, Leon MB, Baim DS, et al. Impact of sirolimus-eluting stents on outcome in diabetic patients: a SIRIUS (SIRolImUS-coated Bx Velocity balloon-expandable stent in the treatment of patients with de novo coronary artery lesions) substudy. Circulation 2004;109:2273-2278.
Abizaid A, Costa MA, Blanchard D, et al. Sirolimus-eluting stents inhibit neointimal hyperplasia in diabetic patients: insights from the RAVEL Trial. Eur Heart J 2004;25:107-112.
DIABETes and sirolimus-Eluting Stent trial: the DIABETES Trial. (Accessed November 1, 2005, at http://www.tctmd.com/csportal/ShowBinary/BEA%20Repository/TCTMD%20Portal/EPSlidePresPool/ExpertPresentation_1111877875569//pdfFile.)
Dr. Windecker and colleagues reply: Drs. Bonvini and Verin correctly outline differences in the definition of target-lesion revascularization between the SIRTAX and TAXUS-IV trials.1 However, SIRTAX was a multilesion trial, and therefore the rate of target-lesion revascularization, reported per patient, should be higher than in a single-lesion study such as TAXUS-IV. The rate of target-lesion revascularization per lesion in SIRTAX was 3.5 percent for the sirolimus group and 5.9 percent for the paclitaxel group. The following considerations further substantiate our findings. First, the SIRTAX definition of target-lesion revascularization is common to many coronary-stent trials,2 including SIRIUS, and reflects clinical practice to intervene in symptomatic patients with stenoses of 50 percent or more. Second, severe late loss (1.2 mm) occurred more frequently with paclitaxel than with sirolimus stents (10.7 percent vs. 5.8 percent, P=0.02). Third, differences in rates of target-lesion revascularization persisted after a post hoc analysis disregarding revascularization driven exclusively by angiography (4.4 percent in the sirolimus-stent group vs. 7.1 percent in the paclitaxel-stent group, P=0.07). Fourth, rates of target-vessel failure at six months (4.2 percent in the sirolimus-stent group vs. 7.1 percent in the paclitaxel-stent group, P=0.05) were different before follow-up angiography and similar to those in BASKET (Basel Stent Cost-Effectiveness Trial),3 another trial comparing sirolimus and paclitaxel stents in a real-world setting (5.7 percent vs. 8.5 percent, P not significant). Fifth, a meta-analysis of six randomized trials comparing sirolimus and paclitaxel stents4 showed rates of target-lesion revascularization (5.1 percent in the sirolimus-stent group vs. 7.8 percent in the paclitaxel-stent group, P=0.001) that were similar to those in SIRTAX.
Stephan Windecker, M.D.
Peter Jüni, M.D.
Bernhard Meier, M.D.
University Hospital Bern
3010 Bern, Switzerland
stephan.windecker@insel.ch
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.
Cutlip DE, Chauhan MS, Baim DS, et al. Clinical restenosis after coronary stenting: perspectives from multicenter clinical trials. J Am Coll Cardiol 2002;40:2082-2089.
Kaiser C, Brunner-La Rocca HP, Buser PT, et al. Incremental cost-effectiveness of drug-eluting stents compared with a third-generation bare-metal stent in a real-world setting: randomised Basel Stent Kosten Effektivitats Trial (BASKET). Lancet 2005;366:921-929.
Kastrati A, Dibra A, Eberle S, et al. Sirolimus-eluting stents vs paclitaxel-eluting stents in patients with coronary artery disease: meta-analysis of randomized trials. JAMA 2005;294:819-825.
Dr. Moliterno replies: The sharply contrasting views of respected leaders, as illustrated by the letters of Drs. Waksman and Wolfram and Dr. Jneid et al., demonstrate the need for large-scale trials in the era of drug-eluting stents. My interpretation of SIRTAX and ISAR-DIABETES is supported by a separate meta-analysis.1 This study included all randomized head-to-head trials of drug-eluting stents and 3669 patients (5 percent from a single-center trial, 58 percent from two-center trials, and 37 percent from a multicenter trial). The odds ratio for target-vessel revascularization was 0.64 (95 percent confidence interval, 0.49 to 0.84) favoring the sirolimus-eluting stent. Although the largest study, REALITY,2 found no difference between the stents, it did have low rates of late luminal loss and revascularization. The odds ratio for target-vessel revascularization in the REALITY trial was 0.92 (95 percent confidence interval, 0.57 to 1.49), favoring the sirolimus-eluting stent, and fits within the confidence intervals of all the previous trials, suggesting that it is in fact consistent with them.
With respect to the comments of Jneid et al.: the overall odds ratio for target-vessel revascularization of 0.64 translates into a 34 percent reduction in risk with sirolimus-eluting stents, which is comparable to the reduction in restenosis provided by bare-metal stents as compared with balloon angioplasty. As noted by Drs. Waksman and Wolfram, the data driving this difference in target-vessel revascularization are from a limited number of study centers. So, if we choose to look most skeptically at these results and consider only the upper confidence limit, the relative risk reduction could be as low as 14 percent and the absolute risk reduction would be as low as 1.1 percent. This weakest-effect scenario means that approximately 90 patients would need to be treated with a sirolimus-eluting stent, rather than a paclitaxel-eluting stent, to prevent one additional target-vessel revascularization. Yet, among patient groups with higher rates of average late luminal loss and clinical restenosis, the benefit of sirolimus-eluting stents appears more distinct.
Jneid et al. disagree with my notion that the Taxus stent has an edge in deliverability. Admittedly, I based this view on my personal experience and that of many colleagues. I do not agree that the similar rates of successful stent implantation from a selected cohort indicate similar deliverability. We would have to presume that the guide support, wire stiffness, extent of predilation, and procedural fluoroscopic times were the same in order for these two stents to be deemed similar in this regard.
David J. Moliterno, M.D.
University of Kentucky
Lexington, KY 40536
moliterno@uky.edu
References
Kastrati A, Dibra A, Eberle S, et al. Sirolimus-eluting stents vs paclitaxel-eluting stents in patients with coronary artery disease: meta-analysis of randomized trials. JAMA 2005;294:819-825.
Morice M-C, Serruys PW, Colombo A, et al. Eight-month outcome of the REALITY Study: a prospective, randomized, multi-center head-to-head comparison of the sirolimus-eluting stent (Cypher) and the paclitaxel-eluting stent (Taxus). Presented at the 2005 Annual Scientific Session of the American College of Cardiology, Orlando, Fla., March 6–9, 2005. (文章出处：《新英格兰医药杂志》)
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