Drug-Eluting Stents in Acute Myocardial Infarction
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《新英格兰医药杂志》
Primary percutaneous coronary intervention (PCI), when performed by an experienced team in a timely fashion, is a better reperfusion therapy than in-hospital thrombolysis in patients who have acute myocardial infarction with ST-segment elevation.1,2 Although randomized trials of primary balloon angioplasty and primary stenting have not demonstrated a mortality benefit of primary stenting and have shown conflicting results with regard to the risk of reinfarction,3,4 primary stenting of the infarct-related lesion has become standard treatment in most patients undergoing primary PCI.
Drug-eluting stents significantly reduce the risks of both restenosis and target-vessel revascularization after elective PCI, as compared with uncoated stents.5,6 Whether drug-eluting stents are also beneficial in the setting of primary PCI has been studied only in relatively small trials, just one of which randomly assigned patients prospectively.7 In this study, the composite end point of death, nonfatal reinfarction, stroke, or restenosis at 8 months was significantly lower among the 74 patients who received sirolimus-eluting stents than it was among the 74 patients who received uncoated stents (hazard ratio, 0.33; 95% confidence interval , 0.18 to 0.60; P<0.001). No significant differences in the rates of reinfarction or death were observed.
In this issue of the Journal, two randomized studies compare drug-eluting stents with uncoated stents in a relatively large population of patients who had acute myocardial infarction with ST-segment elevation and who were undergoing primary PCI.8,9 In the Paclitaxel-Eluting Stent versus Conventional Stent in Myocardial Infarction with ST-Segment Elevation (PASSION) trial, Laarman et al.8 randomly assigned 619 patients from two centers who presented with acute myocardial infarction with ST-segment elevation to receive a paclitaxel-eluting stent (Taxus Express2, Boston Scientific) or an uncoated stent (either Express2 or Liberté, both from Boston Scientific). The primary end point was a composite of death from cardiac causes, reinfarction requiring hospitalization, and ischemia-driven target-lesion revascularization within 12 months. No routine follow-up angiography was performed. The primary end point occurred in 8.8% of patients who received a paclitaxel-eluting stent, as compared with 12.8% of those who received an uncoated stent. This difference did not reach statistical significance (adjusted relative risk, 0.63; 95% CI, 0.37 to 1.07; P=0.09). Nonsignificant trends in favor of the paclitaxel-eluting stent, as compared with the uncoated stent, were observed for each of the components of the primary end point: death from cardiac causes (3.9% vs. 6.2%), reinfarction (1.7% vs. 2.0%), and target-lesion revascularization (5.3% vs. 7.8%). One late in-stent thrombosis was observed in the paclitaxel group and none in the uncoated-stent group.
In the Trial to Assess the Use of the Cypher Stent in Acute Myocardial Infarction Treated with Balloon Angioplasty (TYPHOON), Spaulding et al.9 randomly assigned 712 patients from 48 centers to receive a sirolimus-eluting stent (Cypher or Cypher Select, Cordis, Johnson & Johnson) or any commercially available uncoated stent. The primary end point was the composite of target-vessel–related death, reinfarction, and target-vessel revascularization at 1 year. After 8 months, follow-up angiography was performed among 174 patients. A significantly lower rate of target-vessel failure at 1 year was observed in the sirolimus-stent group than in the uncoated-stent group (7.3% vs. 14.3%, P=0.004). This difference was driven by a significant reduction in the rate of target-vessel revascularization in the sirolimus-stent group, as compared with the uncoated-stent group (5.6% vs. 13.4%, P<0.001), since rates of death (2.3% in the sirolimus-stent group and 2.2% in the uncoated-stent group) and reinfarction (1.1% and 1.4%, respectively) were almost identical. The total rates of in-stent thrombosis were also similar (3.4% and 3.6%, respectively); late stent thrombosis occurred in one patient in the sirolimus-stent group and in two patients in the uncoated-stent group. The rate of restenosis was lower in the sirolimus-stent group than in the uncoated-stent group in the angiographic substudy, a finding that was consistent with the lower overall rate of target-vessel revascularization in the sirolimus-stent group.
Thus, in the PASSION trial, nonsignificant trends in favor of the paclitaxel-eluting stent were found for target-lesion revascularization, death, and reinfarction, whereas in the TYPHOON trial, the sirolimus-eluting stent was associated with a significant reduction in the rate of target-vessel revascularization, with rates of death and reinfarction very similar to those in the uncoated-stent group. It would be dangerous to conclude from these data that one drug-eluting stent is better than the other in primary PCI, since direct comparisons of the two stents for this indication are not available. In the two studies, the design, inclusion criteria, and definitions of end points were indeed slightly different. Yet, the results seem to be in line with those of studies that have compared these two types of stents in elective procedures — namely, lower rates of restenosis and repeated intervention with the sirolimus-eluting stent without significant differences in myocardial infarction or death.10,11 An alternative explanation for the different effect on repeated revascularization could be the use of particular uncoated stents. In the PASSION trial, two specific uncoated stents were used (making the polymer and paclitaxel the only difference between the two groups), whereas in the TYPHOON trial, any uncoated stent was allowed. This discrepancy may explain why the rates of repeated revascularization in the uncoated-stent group were higher in the TYPHOON trial than in the PASSION trial (13.4% vs. 7.8%). It also may explain the statistical difference in this end point, since the rates of revascularization for the drug-eluting stents were remarkably similar (5.6% for sirolimus and 5.3% for paclitaxel). Furthermore, the performance of follow-up angiography among 174 patients may have triggered additional revascularization procedures in the TYPHOON trial.
In conclusion, the data from these two trials indicate that drug-eluting stents can be used safely in the setting of primary PCI and are likely to reduce the need for repeated revascularization. However, the results do not demonstrate that criteria for selecting a drug-eluting stent for this indication should differ from those for elective procedures (e.g., diabetes, long lesions, and small vessels). Because of the cost, the need for prolonged treatment with thienopyridine, and the risk of late stent thrombosis (especially after premature discontinuation of thienopyridine therapy12), larger trials with hard clinical end points and longer follow-up are needed before routine implantation of drug-eluting stents can be recommended for all patients undergoing primary PCI.
No potential conflict of interest relevant to this article was reported.
Source Information
From the University of Leuven, Leuven, Belgium.
References
Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 2003;361:13-20.
Boersma E. Does time matter? A pooled analysis of randomized clinical trials comparing primary percutaneous coronary intervention and in-hospital fibrinolysis in acute myocardial infarction patients. Eur Heart J 2006;27:779-788.
Nordmann AJ, Hengstler P, Harr T, Young J, Bucher HC. Clinical outcomes of primary stenting versus balloon angioplasty in patients with myocardial infarction: a meta-analysis of randomized controlled trials. Am J Med 2004;116:253-262.
Zhu MM, Feit A, Chadow H, Alam M, Kwan T, Clark LT. Primary stent implantation compared with primary balloon angioplasty for acute myocardial infarction: a meta-analysis of randomized clinical trials. Am J Cardiol 2001;88:297-301.
Morice M-C, Serruys PW, Sousa JE, et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 2002;346:1773-1780.
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.
Valgimigli M, Percoco G, Malagutti P, et al. Tirofiban and sirolimus-eluting stent vs abciximab and bare-metal stent for acute myocardial infarction: a randomized trial. JAMA 2005;293:2109-2117.
Laarman GJ, Suttorp MJ, Dirksen MT, et al. Paclitaxel-eluting versus uncoated stents in primary percutaneous coronary intervention. N Engl J Med 2006;355:1105-1113.
Spaulding C, Henry P, Teiger E, et al. Sirolimus-eluting versus uncoated stents in acute myocardial infarction. N Engl J Med 2006;355:1093-1104.
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 MC, Colombo A, Meier B, et al. Sirolimus- vs paclitaxel-eluting stents in de novo coronary artery lesions: the REALITY trial: a randomized controlled trial. JAMA 2006;295:895-904.
Spertus JA, Kettelkamp R, Vance C, et al. Prevalence, predictors, and outcomes of premature discontinuation of thienopyridine therapy after drug-eluting stent placement: results from the PREMIER registry. Circulation 2006;113:2803-2809.(Frans Van de Werf, M.D., )
Drug-eluting stents significantly reduce the risks of both restenosis and target-vessel revascularization after elective PCI, as compared with uncoated stents.5,6 Whether drug-eluting stents are also beneficial in the setting of primary PCI has been studied only in relatively small trials, just one of which randomly assigned patients prospectively.7 In this study, the composite end point of death, nonfatal reinfarction, stroke, or restenosis at 8 months was significantly lower among the 74 patients who received sirolimus-eluting stents than it was among the 74 patients who received uncoated stents (hazard ratio, 0.33; 95% confidence interval , 0.18 to 0.60; P<0.001). No significant differences in the rates of reinfarction or death were observed.
In this issue of the Journal, two randomized studies compare drug-eluting stents with uncoated stents in a relatively large population of patients who had acute myocardial infarction with ST-segment elevation and who were undergoing primary PCI.8,9 In the Paclitaxel-Eluting Stent versus Conventional Stent in Myocardial Infarction with ST-Segment Elevation (PASSION) trial, Laarman et al.8 randomly assigned 619 patients from two centers who presented with acute myocardial infarction with ST-segment elevation to receive a paclitaxel-eluting stent (Taxus Express2, Boston Scientific) or an uncoated stent (either Express2 or Liberté, both from Boston Scientific). The primary end point was a composite of death from cardiac causes, reinfarction requiring hospitalization, and ischemia-driven target-lesion revascularization within 12 months. No routine follow-up angiography was performed. The primary end point occurred in 8.8% of patients who received a paclitaxel-eluting stent, as compared with 12.8% of those who received an uncoated stent. This difference did not reach statistical significance (adjusted relative risk, 0.63; 95% CI, 0.37 to 1.07; P=0.09). Nonsignificant trends in favor of the paclitaxel-eluting stent, as compared with the uncoated stent, were observed for each of the components of the primary end point: death from cardiac causes (3.9% vs. 6.2%), reinfarction (1.7% vs. 2.0%), and target-lesion revascularization (5.3% vs. 7.8%). One late in-stent thrombosis was observed in the paclitaxel group and none in the uncoated-stent group.
In the Trial to Assess the Use of the Cypher Stent in Acute Myocardial Infarction Treated with Balloon Angioplasty (TYPHOON), Spaulding et al.9 randomly assigned 712 patients from 48 centers to receive a sirolimus-eluting stent (Cypher or Cypher Select, Cordis, Johnson & Johnson) or any commercially available uncoated stent. The primary end point was the composite of target-vessel–related death, reinfarction, and target-vessel revascularization at 1 year. After 8 months, follow-up angiography was performed among 174 patients. A significantly lower rate of target-vessel failure at 1 year was observed in the sirolimus-stent group than in the uncoated-stent group (7.3% vs. 14.3%, P=0.004). This difference was driven by a significant reduction in the rate of target-vessel revascularization in the sirolimus-stent group, as compared with the uncoated-stent group (5.6% vs. 13.4%, P<0.001), since rates of death (2.3% in the sirolimus-stent group and 2.2% in the uncoated-stent group) and reinfarction (1.1% and 1.4%, respectively) were almost identical. The total rates of in-stent thrombosis were also similar (3.4% and 3.6%, respectively); late stent thrombosis occurred in one patient in the sirolimus-stent group and in two patients in the uncoated-stent group. The rate of restenosis was lower in the sirolimus-stent group than in the uncoated-stent group in the angiographic substudy, a finding that was consistent with the lower overall rate of target-vessel revascularization in the sirolimus-stent group.
Thus, in the PASSION trial, nonsignificant trends in favor of the paclitaxel-eluting stent were found for target-lesion revascularization, death, and reinfarction, whereas in the TYPHOON trial, the sirolimus-eluting stent was associated with a significant reduction in the rate of target-vessel revascularization, with rates of death and reinfarction very similar to those in the uncoated-stent group. It would be dangerous to conclude from these data that one drug-eluting stent is better than the other in primary PCI, since direct comparisons of the two stents for this indication are not available. In the two studies, the design, inclusion criteria, and definitions of end points were indeed slightly different. Yet, the results seem to be in line with those of studies that have compared these two types of stents in elective procedures — namely, lower rates of restenosis and repeated intervention with the sirolimus-eluting stent without significant differences in myocardial infarction or death.10,11 An alternative explanation for the different effect on repeated revascularization could be the use of particular uncoated stents. In the PASSION trial, two specific uncoated stents were used (making the polymer and paclitaxel the only difference between the two groups), whereas in the TYPHOON trial, any uncoated stent was allowed. This discrepancy may explain why the rates of repeated revascularization in the uncoated-stent group were higher in the TYPHOON trial than in the PASSION trial (13.4% vs. 7.8%). It also may explain the statistical difference in this end point, since the rates of revascularization for the drug-eluting stents were remarkably similar (5.6% for sirolimus and 5.3% for paclitaxel). Furthermore, the performance of follow-up angiography among 174 patients may have triggered additional revascularization procedures in the TYPHOON trial.
In conclusion, the data from these two trials indicate that drug-eluting stents can be used safely in the setting of primary PCI and are likely to reduce the need for repeated revascularization. However, the results do not demonstrate that criteria for selecting a drug-eluting stent for this indication should differ from those for elective procedures (e.g., diabetes, long lesions, and small vessels). Because of the cost, the need for prolonged treatment with thienopyridine, and the risk of late stent thrombosis (especially after premature discontinuation of thienopyridine therapy12), larger trials with hard clinical end points and longer follow-up are needed before routine implantation of drug-eluting stents can be recommended for all patients undergoing primary PCI.
No potential conflict of interest relevant to this article was reported.
Source Information
From the University of Leuven, Leuven, Belgium.
References
Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 2003;361:13-20.
Boersma E. Does time matter? A pooled analysis of randomized clinical trials comparing primary percutaneous coronary intervention and in-hospital fibrinolysis in acute myocardial infarction patients. Eur Heart J 2006;27:779-788.
Nordmann AJ, Hengstler P, Harr T, Young J, Bucher HC. Clinical outcomes of primary stenting versus balloon angioplasty in patients with myocardial infarction: a meta-analysis of randomized controlled trials. Am J Med 2004;116:253-262.
Zhu MM, Feit A, Chadow H, Alam M, Kwan T, Clark LT. Primary stent implantation compared with primary balloon angioplasty for acute myocardial infarction: a meta-analysis of randomized clinical trials. Am J Cardiol 2001;88:297-301.
Morice M-C, Serruys PW, Sousa JE, et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 2002;346:1773-1780.
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.
Valgimigli M, Percoco G, Malagutti P, et al. Tirofiban and sirolimus-eluting stent vs abciximab and bare-metal stent for acute myocardial infarction: a randomized trial. JAMA 2005;293:2109-2117.
Laarman GJ, Suttorp MJ, Dirksen MT, et al. Paclitaxel-eluting versus uncoated stents in primary percutaneous coronary intervention. N Engl J Med 2006;355:1105-1113.
Spaulding C, Henry P, Teiger E, et al. Sirolimus-eluting versus uncoated stents in acute myocardial infarction. N Engl J Med 2006;355:1093-1104.
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 MC, Colombo A, Meier B, et al. Sirolimus- vs paclitaxel-eluting stents in de novo coronary artery lesions: the REALITY trial: a randomized controlled trial. JAMA 2006;295:895-904.
Spertus JA, Kettelkamp R, Vance C, et al. Prevalence, predictors, and outcomes of premature discontinuation of thienopyridine therapy after drug-eluting stent placement: results from the PREMIER registry. Circulation 2006;113:2803-2809.(Frans Van de Werf, M.D., )