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A randomized trial of polytetrafluoroethylene-membrane-covered stents compared with conventional stents in aortocoronary saphenous vein grafts
Conclusions: The authors conclude that compared with a bare metal stent, paclitaxel-eluting stents reduced in-stent neointimal formation and restenosis and improved 12month clinical outcome of patients with single de novo coronary lesions. Perspective: This trial showed that polymer-controlled slow and moderate release of paclitaxel reduces neointimal obstruction within the stent by 64% as measured by IVUS, angiographic restenosis by 73% and 74%, respectively, and 6- and 12-month MACE rates by 50% and 54% because of reductions in target-lesion revascularizations of 64% and 76%, respectively. The favorable impact on restenosis are similar in magnitude to recent reports on a sirolimus-coated stent system. The similar efficacy profiles of the two formulations may suggest that the dosing threshold to reduce restenosis is reached with the slow-release paclitaxel formulation, at least in low-risk, elective patients. DM
clinical events in patients with complex coronary lesions. Similar promising results have also been demonstrated with paclitaxel-coated stents in the TAXUS trials and the overall 9-month outcome of the drug-eluting stent group is similar between TAXUS IV and the SIRIUS trial (7.9% vs. 8.9% restenosis rate). A head-to-head comparison of the stents used in these trials is being planned and may help define the relative advantages of each stent. Future longer-term studies in larger cohorts are required to assess durability, effectiveness in other high-risk subsets of patients and costeffectiveness of this impressive therapy. A lingering concern in this and other trials of drug eluting stents is that trends for their effect on both MI and death are in the wrong direction. Stent thrombosis may be a particular concern with incomplete deployment. DM
Randomized Study to Assess the Effectiveness of Slow- and Moderate-Release Polymer-Based Paclitaxel-Eluting Stents for Coronary Artery Lesions
A Randomized Trial of PolytetrafluoroethyleneMembrane-Covered Stents Compared With Conventional Stents in Aortocoronary Saphenous Vein Grafts
Colombo A, Drzewiecki J, Banning A, et al., for the TAXUS II Study Group. Circulation 2003;108:788 –94.
Schachinger V, Hamm CW, Munzel T, et al., for the STING (Stents IN Grafts) Investigators. J Am Coll Cardiol 2003;42: 1360 –9.
Study Question: The study evaluated the safety and efficacy of two different release formulations of a paclitaxel-eluting stent in a group of patients. In addition, the study addressed four key issues associated with drug-eluting stents: stent thrombosis, edge restenosis, incomplete apposition and aneurysm formation. Methods: The study was a randomized, double-blind trial of 536 patients at 38 medical centers evaluating slow-release (SR) and moderate-release (MR) formulations of a polymerbased paclitaxel-eluting stent (TAXUS) for revascularization of single primary lesions in native coronary arteries. Cohort I compared TAXUS-SR with control stents, and Cohort II compared TAXUS-MR with a second control group. The primary end point was 6-month percent instent net volume obstruction measured by intravascular ultrasound. Secondary end points were 6-month angiographic restenosis and 6- and 12-month incidence of major adverse cardiac events [MACE], a composite of cardiac death, myocardial infarction and repeat revascularization. Results: At 6 months, percent net volume obstruction within the stent was significantly lower for TAXUS stents (7.9% SR and 7.8% MR) than for respective controls (23.2% and 20.5%; p⬍0.0001 for both). This corresponded with a reduction in angiographic restenosis from 17.9% to 2.3% in the SR cohort (p⬍0.0001) and from 20.2% to 4.7% in the MR cohort (p⫽0.0002). The incidence of major adverse cardiac events at 12 months was significantly lower (p⫽0.0192) in the TAXUS-SR (10.9%) and TAXUS-MR (9.9%) groups than in controls (22.0% and 21.4%, respectively), predominantly because of a significant reduction in repeat revascularization of the target lesion in TAXUS-treated patients.
Study Question: The investigators compared a conventional stent (Jostent Flex) with a polytetrafluoroethylene (PTFE)membrane-covered stent (Jostent Stentgraft) in patients undergoing vein graft intervention to assess superiority of covered stents. Methods: The study was a prospective multicenter study and included a total of 211 patients who were randomly assigned to receive either a Flex stent or Stentgraft. The primary end point was binary restenosis rate at 6 months by core lab quantitative coronary angiography. Results: Acute success and procedural events were comparable between the two groups. Restenosis rate was not significantly different between the Flex (20%) and the Stentgraft (29%) groups (p⫽0.15), although there was a nonsignificant trend toward a higher late occlusion rate in the Stentgraft group (7% vs. 16%, p⫽0.069) at follow-up. Likewise, after a mean observation period of 14 months, cumulative event rates (death, myocardial infarction or target lesion revascularization) were comparable in the two groups (31% vs. 31%, p⫽0.93). Conclusions: The authors concluded that this controlled trial does not indicate a superiority of the PTFE-membranecovered Stentgraft compared with a conventional stent with respect to acute results, restenosis or clinical event rates. Perspective: The current study demonstrates no advantage of stent grafts compared with conventional stents with respect to restenosis or clinical events in vein graft PCI. In fact, there was a trend toward a higher rate of total occlusions at follow-up in the stent graft group. The results are
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consistent with the results of the RECOVERS trial, which also failed to show any benefit of PTFE-covered stents in vein graft PCI. DM
treatment did not improve outcome compared with immediate intervention/revascularization accompanied by intense antiplatelet treatment. In patients with unstable coronary syndromes, the goal should be early cardiac catheterization and revascularization. DM
Evaluation of Prolonged Antithrombotic Pretreatment (“Cooling-Off” Strategy) Before Intervention in Patients With Unstable Coronary Syndromes
Mortality Risk Conferred by Small Elevations of Creatine Kinase-MB Isoenzyme After Percutaneous Coronary Intervention
Neumann FJ, Kastrati A, Pogatsa-Murray G, et al. JAMA 2003; 290:1593–9.
Ioannidis JPA, Karvouni E, Katritsis DG. J Am Coll Cardiol 2003; 42:1406 –11.
Study Question: The investigators tested the hypothesis whether prolonged antithrombotic pretreatment improves the outcome of catheter intervention in patients with acute unstable coronary syndromes compared with early intervention. Methods: The study was a randomized controlled trial enrolling patients admitted with symptoms of unstable angina plus either ST-segment depression or elevation of cardiac troponin T levels. Patients were randomly allocated to antithrombotic pretreatment for 3–5 days or to early intervention after pretreatment for less than 6 hours. In both groups, antithrombotic pretreatment consisted of intravenous unfractionated heparin (60-U/kg bolus followed by infusion adjusted to maintain partial thromboplastin time of 60 – 85 seconds), aspirin (500-mg intravenous bolus followed by 100-mg twice-daily oral dose), oral clopidogrel (600-mg loading dose followed by 75-mg twice-daily dose) and intravenous tirofiban (10-g/kg bolus followed by continuous infusion of 0.10 g/kg per min). Of the 410 patients enrolled, 207 were allocated to receive prolonged antithrombotic pretreatment and 203 to receive early intervention. The primary end point was a composite 30-day incidence of large nonfatal myocardial infarction or death from any cause. Results: The antithrombotic pretreatment and the early intervention groups were well matched with respect to major baseline characteristics and definitive treatment (catheter revascularization: 133 [64.3%] vs. 143 [70.4%], respectively; coronary artery bypass graft surgery: 16 [7.7%] vs. 16 [7.9%]). The primary end point was reached in 11.6% (three deaths, 21 infarctions) of the group receiving prolonged antithrombotic pretreatment and in 5.9% (no deaths, 12 infarctions) of the group receiving early intervention (relative risk, 1.96 [95% confidence interval, 1.01–3.82]; p⫽0.04). This outcome was attributable to events occurring before catheterization; after catheterization, both groups incurred 11 events each (p⫽0.92). Conclusions: The authors concluded that in patients with unstable coronary syndromes, deferral of intervention for prolonged antithrombotic pretreatment does not improve the outcome compared with immediate intervention accompanied by intense antiplatelet treatment. Perspective: This randomized controlled trial in patients with unstable coronary syndromes demonstrated that deferral of intervention for prolonged antithrombotic pre-
Study Question: The investigators assessed whether small creatine kinase-MB isoenzyme (CK-MB) elevations after percutaneous coronary intervention (PCI) affect the subsequent mortality risk. Methods: The study was a meta-analysis of seven studies with CK-MB measurements and survival outcomes on 23,230 subjects who underwent PCI. Data were combined with random effects models. Results: Mean follow-up was 6 –34 months per study. By random effects, 19% of patients (95% confidence interval [CI] 16%–23%) had one- to fivefold CK-MB elevations, while only 6% (95% CI, 5–9%) had ⬎fivefold elevations. Compared to subjects with normal CK-MB, there was a dose-response relationship with relative risks for death being 1.5 (95% CI, 1.2–1.8, no between-study heterogeneity) with one- to threefold CK-MB elevations, 1.8 (95% CI, 1.4 –2.4, no between-study heterogeneity) with three- to fivefold CK-MB elevations and 3.1 (95% CI, 2.3– 4.2, borderline between-study heterogeneity) with over fivefold CK-MB elevations (p⬍0.001 for all). Conclusions: The authors concluded that any increase in CK-MB after PCI is associated with a small, but statistically and clinically significant, increase in the subsequent risk of death. Perspective: This meta-analysis based on data from over 23,000 subjects demonstrates the clinical significance of small CK-MB elevations after PCI. Any CK-MB increase appears to be associated with a potential increase in the subsequent risk of death. Given that minor elevations are far more common than more pronounced CK-MB increases, their mortality impact may be considerable in the population of patients undergoing PCI. DM
A Comparison of Two Invasive Strategies in Patients With Non-ST Elevation Acute Coronary Syndromes: Results of the Early or Late Intervention in unStable Angina (ELISA) Pilot Study: 2b/3a Upstream Therapy and Acute Coronary Syndromes van’t Hof AWJ, de Vries ST, Dambrink JE, et al. Eur Heart J 2003;24:1401–5.
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clinical events in patients with complex coronary lesions. Similar promising results have also been demonstrated with paclitaxel-coated stents in the TAXUS trials and the overall 9-month outcome of the drug-eluting stent group is similar between TAXUS IV and the SIRIUS trial (7.9% vs. 8.9% restenosis rate). A head-to-head comparison of the stents used in these trials is being planned and may help define the relative advantages of each stent. Future longer-term studies in larger cohorts are required to assess durability, effectiveness in other high-risk subsets of patients and costeffectiveness of this impressive therapy. A lingering concern in this and other trials of drug eluting stents is that trends for their effect on both MI and death are in the wrong direction. Stent thrombosis may be a particular concern with incomplete deployment. DM
Randomized Study to Assess the Effectiveness of Slow- and Moderate-Release Polymer-Based Paclitaxel-Eluting Stents for Coronary Artery Lesions
A Randomized Trial of PolytetrafluoroethyleneMembrane-Covered Stents Compared With Conventional Stents in Aortocoronary Saphenous Vein Grafts
Colombo A, Drzewiecki J, Banning A, et al., for the TAXUS II Study Group. Circulation 2003;108:788 –94.
Schachinger V, Hamm CW, Munzel T, et al., for the STING (Stents IN Grafts) Investigators. J Am Coll Cardiol 2003;42: 1360 –9.
Study Question: The study evaluated the safety and efficacy of two different release formulations of a paclitaxel-eluting stent in a group of patients. In addition, the study addressed four key issues associated with drug-eluting stents: stent thrombosis, edge restenosis, incomplete apposition and aneurysm formation. Methods: The study was a randomized, double-blind trial of 536 patients at 38 medical centers evaluating slow-release (SR) and moderate-release (MR) formulations of a polymerbased paclitaxel-eluting stent (TAXUS) for revascularization of single primary lesions in native coronary arteries. Cohort I compared TAXUS-SR with control stents, and Cohort II compared TAXUS-MR with a second control group. The primary end point was 6-month percent instent net volume obstruction measured by intravascular ultrasound. Secondary end points were 6-month angiographic restenosis and 6- and 12-month incidence of major adverse cardiac events [MACE], a composite of cardiac death, myocardial infarction and repeat revascularization. Results: At 6 months, percent net volume obstruction within the stent was significantly lower for TAXUS stents (7.9% SR and 7.8% MR) than for respective controls (23.2% and 20.5%; p⬍0.0001 for both). This corresponded with a reduction in angiographic restenosis from 17.9% to 2.3% in the SR cohort (p⬍0.0001) and from 20.2% to 4.7% in the MR cohort (p⫽0.0002). The incidence of major adverse cardiac events at 12 months was significantly lower (p⫽0.0192) in the TAXUS-SR (10.9%) and TAXUS-MR (9.9%) groups than in controls (22.0% and 21.4%, respectively), predominantly because of a significant reduction in repeat revascularization of the target lesion in TAXUS-treated patients.
Study Question: The investigators compared a conventional stent (Jostent Flex) with a polytetrafluoroethylene (PTFE)membrane-covered stent (Jostent Stentgraft) in patients undergoing vein graft intervention to assess superiority of covered stents. Methods: The study was a prospective multicenter study and included a total of 211 patients who were randomly assigned to receive either a Flex stent or Stentgraft. The primary end point was binary restenosis rate at 6 months by core lab quantitative coronary angiography. Results: Acute success and procedural events were comparable between the two groups. Restenosis rate was not significantly different between the Flex (20%) and the Stentgraft (29%) groups (p⫽0.15), although there was a nonsignificant trend toward a higher late occlusion rate in the Stentgraft group (7% vs. 16%, p⫽0.069) at follow-up. Likewise, after a mean observation period of 14 months, cumulative event rates (death, myocardial infarction or target lesion revascularization) were comparable in the two groups (31% vs. 31%, p⫽0.93). Conclusions: The authors concluded that this controlled trial does not indicate a superiority of the PTFE-membranecovered Stentgraft compared with a conventional stent with respect to acute results, restenosis or clinical event rates. Perspective: The current study demonstrates no advantage of stent grafts compared with conventional stents with respect to restenosis or clinical events in vein graft PCI. In fact, there was a trend toward a higher rate of total occlusions at follow-up in the stent graft group. The results are
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40
consistent with the results of the RECOVERS trial, which also failed to show any benefit of PTFE-covered stents in vein graft PCI. DM
treatment did not improve outcome compared with immediate intervention/revascularization accompanied by intense antiplatelet treatment. In patients with unstable coronary syndromes, the goal should be early cardiac catheterization and revascularization. DM
Evaluation of Prolonged Antithrombotic Pretreatment (“Cooling-Off” Strategy) Before Intervention in Patients With Unstable Coronary Syndromes
Mortality Risk Conferred by Small Elevations of Creatine Kinase-MB Isoenzyme After Percutaneous Coronary Intervention
Neumann FJ, Kastrati A, Pogatsa-Murray G, et al. JAMA 2003; 290:1593–9.
Ioannidis JPA, Karvouni E, Katritsis DG. J Am Coll Cardiol 2003; 42:1406 –11.
Study Question: The investigators tested the hypothesis whether prolonged antithrombotic pretreatment improves the outcome of catheter intervention in patients with acute unstable coronary syndromes compared with early intervention. Methods: The study was a randomized controlled trial enrolling patients admitted with symptoms of unstable angina plus either ST-segment depression or elevation of cardiac troponin T levels. Patients were randomly allocated to antithrombotic pretreatment for 3–5 days or to early intervention after pretreatment for less than 6 hours. In both groups, antithrombotic pretreatment consisted of intravenous unfractionated heparin (60-U/kg bolus followed by infusion adjusted to maintain partial thromboplastin time of 60 – 85 seconds), aspirin (500-mg intravenous bolus followed by 100-mg twice-daily oral dose), oral clopidogrel (600-mg loading dose followed by 75-mg twice-daily dose) and intravenous tirofiban (10-g/kg bolus followed by continuous infusion of 0.10 g/kg per min). Of the 410 patients enrolled, 207 were allocated to receive prolonged antithrombotic pretreatment and 203 to receive early intervention. The primary end point was a composite 30-day incidence of large nonfatal myocardial infarction or death from any cause. Results: The antithrombotic pretreatment and the early intervention groups were well matched with respect to major baseline characteristics and definitive treatment (catheter revascularization: 133 [64.3%] vs. 143 [70.4%], respectively; coronary artery bypass graft surgery: 16 [7.7%] vs. 16 [7.9%]). The primary end point was reached in 11.6% (three deaths, 21 infarctions) of the group receiving prolonged antithrombotic pretreatment and in 5.9% (no deaths, 12 infarctions) of the group receiving early intervention (relative risk, 1.96 [95% confidence interval, 1.01–3.82]; p⫽0.04). This outcome was attributable to events occurring before catheterization; after catheterization, both groups incurred 11 events each (p⫽0.92). Conclusions: The authors concluded that in patients with unstable coronary syndromes, deferral of intervention for prolonged antithrombotic pretreatment does not improve the outcome compared with immediate intervention accompanied by intense antiplatelet treatment. Perspective: This randomized controlled trial in patients with unstable coronary syndromes demonstrated that deferral of intervention for prolonged antithrombotic pre-
Study Question: The investigators assessed whether small creatine kinase-MB isoenzyme (CK-MB) elevations after percutaneous coronary intervention (PCI) affect the subsequent mortality risk. Methods: The study was a meta-analysis of seven studies with CK-MB measurements and survival outcomes on 23,230 subjects who underwent PCI. Data were combined with random effects models. Results: Mean follow-up was 6 –34 months per study. By random effects, 19% of patients (95% confidence interval [CI] 16%–23%) had one- to fivefold CK-MB elevations, while only 6% (95% CI, 5–9%) had ⬎fivefold elevations. Compared to subjects with normal CK-MB, there was a dose-response relationship with relative risks for death being 1.5 (95% CI, 1.2–1.8, no between-study heterogeneity) with one- to threefold CK-MB elevations, 1.8 (95% CI, 1.4 –2.4, no between-study heterogeneity) with three- to fivefold CK-MB elevations and 3.1 (95% CI, 2.3– 4.2, borderline between-study heterogeneity) with over fivefold CK-MB elevations (p⬍0.001 for all). Conclusions: The authors concluded that any increase in CK-MB after PCI is associated with a small, but statistically and clinically significant, increase in the subsequent risk of death. Perspective: This meta-analysis based on data from over 23,000 subjects demonstrates the clinical significance of small CK-MB elevations after PCI. Any CK-MB increase appears to be associated with a potential increase in the subsequent risk of death. Given that minor elevations are far more common than more pronounced CK-MB increases, their mortality impact may be considerable in the population of patients undergoing PCI. DM
A Comparison of Two Invasive Strategies in Patients With Non-ST Elevation Acute Coronary Syndromes: Results of the Early or Late Intervention in unStable Angina (ELISA) Pilot Study: 2b/3a Upstream Therapy and Acute Coronary Syndromes van’t Hof AWJ, de Vries ST, Dambrink JE, et al. Eur Heart J 2003;24:1401–5.
ACC CURRENT JOURNAL REVIEW Jan 2004
41