[Intracoronary Stenting and Angiographic Results Strut Thickness Effect on Restenosis Outcome (ISAR-STEREO) Trial].

BACKGROUND: Increased thrombogenicity and smooth muscle cell proliferative response induced by the metal struts compromise the advantages of coronary stenting. The objective of this randomized, multicenter study was to ascertain whether a reduced strut thickness of a stent is associated with improved follow-up angiographic and clinical results. METHODS AND RESULTS: The study covered 651 patients with stenosis in the native coronary arteries > 2.8 mm in diameter. They were randomly assigned to receive 1 of 2 commercially available stents of comparable design but different thickness: 326 patients to the thin-strut stent (strut thickness of 50 microm) and 325 patients to the thicker-strut stent (strut thickness of 140 microm). The primary end point was the angiographic restenosis (> or = 50% diameter luminal stenosis at follow-up angiography). The secondary end points were the incidence of reinterventions due to restenosis-induced ischemia and the total rate of death and myocardial infarctions at 1 year (a combined end point). The incidence of angiographic restenosis was 15.0% in the thin-strut group and 25.8% in the thick-strut group (relative risk, 0.58; 95% CI, 0.39 to 0.87; p = 0.003). Clinical restenosis was also significantly reduced. Reinterventions were made in 8.6% of the thin-strut patients and in 13.8% of the thick-strut patients (relative risk, 0.62; 95% CI, 0.39 to 0.99; p = 0.03). No difference was observed in the combined 1-year rate of death and myocardial infarction. CONCLUSIONS: The use of a thin-strut device is associated with a significant reduction of angiographic and clinical restenosis after coronary artery stenting. These findings may have relevant implications for the currently most widely used percutaneous coronary intervention.

Statin effect on thrombin inhibitor effectiveness during percutaneous coronary intervention: a post-hoc analysis from the ISAR-REACT 3 trial.

OBJECTIVE: To determine whether statin therapy influences the efficacy of thrombin inhibitor bivalirudin or unfractionated heparin (UFH) during PCI. SETTING AND PATIENTS: The post-hoc analysis of the ISAR-REACT 3 Trial included 4,570 patients: 3,106 patients were on statin therapy and 1,464 patients were not on statin therapy at the time of PCI procedure. MAIN OUTCOME MEASURES: The primary outcome of this analysis was the 30-day composite of death, myocardial infarction, target vessel revascularization (TVR) or major bleeding. RESULTS: The primary outcome occurred in 7.9% patients (n = 246) in the statin group versus 9.8% (n = 143) in the non-statin group (P = 0.036). There was an interaction in univariate (P = 0.028) and multivariable (P = 0.026) analysis between pre-PCI statin therapy and the type of antithrombotic therapy regarding myocardial infarction. In the statin group, bivalirudin significantly reduced the incidence of major bleeding (2.6 vs. 4.3%, P = 0.013) with no significant difference in the incidence of myocardial infarction (4.9 vs. 5.2%; P = 0.73) compared with UFH. In the non-statin group, bivalirudin was inferior to UFH regarding the incidence of myocardial infarction (7.1 vs. 4.1%, P = 0.013), yet major bleeding remained lower among bivalirudin-treated patients (4.0 vs. 5.2%, P = 0.25). CONCLUSION: This post-hoc analysis suggests the existence of an interaction between statin therapy before PCI and antithrombotic therapy during PCI. Patients receiving bivalirudin therapy at the time of PCI showed less periprocedural myocardial infarction when on pre-PCI statin therapy which has to be investigated in further studies.

Erythropoietin in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a randomized, double-blind trial.

BACKGROUND: Erythropoietin improves myocardial function in experimental models of myocardial infarction. The aim of the present study was to determine the value of erythropoietin in patients with acute ST-elevation myocardial infarction. METHODS AND RESULTS: This randomized, double-blind study included 138 patients admitted with acute ST-elevation myocardial infarction and treated with primary percutaneous coronary intervention. Patients were randomly assigned to receive epoetin-ß (3.33×104 U, n=68) or placebo (n=70) immediately and at 24 and 48 hours after percutaneous coronary intervention. The primary end point was left ventricular ejection fraction after 6 months measured by MRI. Other end points included infarct size at 5 days and 6 months. Clinical adverse events (death, recurrent myocardial infarction, stroke, and infarct-related artery revascularization) were investigated at 30 days and 6 months. Left ventricular ejection fraction at 6-month follow-up was 52.0±9.1% in the erythropoietin group compared with 51.8±9.3% in the placebo group (P=0.92). Five days after percutaneous coronary intervention, left ventricular ejection fraction was 49.4±8.0% in the erythropoietin group and 50.8±7.3% in the placebo group (P=0.32); infarct size was 26.8±20.9% and 28.3±24.4% (P=0.76) and decreased to 17.3±14.3% and 20.9±16.4% at 6-month follow-up (P=0.27). The cumulative 6-month incidence of death, recurrent myocardial infarction, stroke or target vessel revascularization was 13.2% in the erythropoietin group and 5.7% in the placebo group (hazard ratio, 2.36; 95% confidence interval, 0.73 to 7.66; P=0.15). CONCLUSIONS: In patients with acute ST-elevation myocardial infarction treated with primary percutaneous coronary intervention, erythropoietin treatment did not improve left ventricular ejection fraction or reduce infarct size but may increase clinical adverse events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00390832.

One-year clinical outcomes with abciximab in acute myocardial infarction: results of the BRAVE-3 randomized trial.

PURPOSE: In the Bavarian Reperfusion Alternatives Evaluation (BRAVE)-3 study upstream administration of abciximab additional to 600 mg clopidogrel loading did not reduce the infarct size in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary interventions. The aim of this study was to investigate 1-year clinical outcomes in the BRAVE-3 study patients. METHODS: A total of 800 patients with acute STEMI within 24 h from symptom onset, all treated with 600 mg of clopidogrel were randomized in a double-blind fashion to receive either abciximab (n = 401) or placebo (n = 399) in the intensive care unit before being sent to the catheterization laboratory. RESULTS: The main outcome of interest of the present study, the composite of death, recurrent myocardial infarction, stroke or revascularization of the infarct-related artery (IRA) at 1 year, was 23.0% (92 patients) in the abciximab versus 25.7% (102 patients) in the placebo group [relative risk (RR) = 0.90, 95% confidence interval (CI) 0.67-1.20; P = 0.46]. The combined incidence of death, recurrent myocardial infarction or stroke was 9.3% in the abciximab group versus 6.0% in the placebo group (RR = 1.55, 95% CI 0.93-2.58; P = 0.09). There was a significant reduction of the IRA revascularization with abciximab compared to placebo (16.3 vs. 22.3%, RR = 0.71, 95% CI 0.52-0.98; P = 0.04). CONCLUSION: In patients with STEMI, all receiving 600 mg clopidogrel, abciximab did not improve overall clinical outcomes at 1 year after primary coronary stenting.

Paclitaxel- versus sirolimus-eluting stents for unprotected left main coronary artery disease.

OBJECTIVES: The aim of this trial was to compare the safety and efficacy of paclitaxel-eluting stents (PES) and sirolimus-eluting stents (SES) for treatment of unprotected left main coronary artery (uLMCA) disease. BACKGROUND: Both PES and SES have reduced the risk of restenosis, particularly in high-risk patient and lesion subsets. However, their comparative performance in uLMCA lesions is not known. METHODS: In this randomized study, 607 patients with symptomatic coronary artery disease undergoing percutaneous coronary intervention for uLMCA were enrolled: 302 were assigned to receive a PES (Taxus, Boston Scientific, Natick, Massachusetts) and 305 assigned to receive a SES (Cypher, Cordis, Johnson & Johnson, New Brunswick, New Jersey). The primary end point was the combined incidence of death, myocardial infarction, and target lesion revascularization (TLR) at 1 year. The secondary end point was angiographic restenosis on the basis of the LMCA area analysis at follow-up angiography. RESULTS: At 1 year the cumulative incidence of death, myocardial infarction, or TLR was 13.6% in the PES and 15.8% in the SES group (relative risk [RR]: 0.85, 95% confidence interval [CI]: 0.56 to 1.29, p = 0.44). One patient in the PES group (0.3%) and 2 patients in the SES group (0.7%) experienced definite stent thrombosis (p = 0.57). Mortality at 2 years was 10.7% in the PES and 8.7% in the SES group (RR: 1.14, 95% CI: 0.66 to 1.95, p = 0.64). Angiographic restenosis was 16.0% with PES and 19.4% with SES (RR: 0.82, 95% CI: 0.57 to 1.19, p = 0.30). CONCLUSIONS: Implantation of either PES or SES in uLMCA lesions is safe and effective; both of these drug-eluting stents provide comparable clinical and angiographic outcomes. (Drug-Eluting-Stents for Unprotected Left Main Stem Disease [ISAR-LEFT-MAIN]; NCT00133237).

Abciximab in patients with acute ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention after clopidogrel loading: a randomized double-blind trial.

BACKGROUND: The glycoprotein IIb/IIIa receptor inhibitor abciximab has improved the efficacy of primary percutaneous coronary interventions in patients with acute myocardial infarction. However, it is not known whether abciximab remains beneficial after adequate clopidogrel loading in patients with acute ST-segment-elevation myocardial infarction. METHODS AND RESULTS: A total of 800 patients with acute ST-segment-elevation myocardial infarction within 24 hours from symptom onset, all treated with 600 mg clopidogrel, were randomly assigned in a double-blind fashion to receive either abciximab (n=401) or placebo (n=399) in the intensive care unit before being sent to the catheterization laboratory. The primary end point, infarct size measured by single-photon emission computed tomography with technetium-99m sestamibi before hospital discharge, was 15.7+/-17.2% (mean+/-SD) of the left ventricle in the abciximab group and 16.6+/-18.6% of the left ventricle in the placebo group (P=0.47). At 30 days, the composite of death, recurrent myocardial infarction, stroke, or urgent revascularization of the infarct-related artery was observed in 20 patients in the abciximab group (5.0%) and 15 patients in the placebo group (3.8%) (relative risk, 1.3; 95% CI, 0.7 to 2.6; P=0.40). Major bleeding complications were observed in 7 patients in each group (1.8%). CONCLUSIONS: Upstream administration of abciximab is not associated with a reduction in infarct size in patients presenting with acute myocardial infarction within 24 hours of symptom onset and receiving 600 mg clopidogrel.

A randomized clinical trial to evaluate the safety and efficacy of a percutaneous left ventricular assist device versus intra-aortic balloon pumping for treatment of cardiogenic shock caused by myocardial infarction.

OBJECTIVES: The aim of this study was to test whether the left ventricular assist device (LVAD) Impella LP2.5 (Abiomed Europe GmbH, Aachen, Germany) provides superior hemodynamic support compared with the intra-aortic balloon pump (IABP). BACKGROUND: Cardiogenic shock caused by left ventricular failure is associated with high mortality in patients with acute myocardial infarction (AMI). An LVAD may help to bridge patients to recovery from left ventricular failure. METHODS: In a prospective, randomized study, 26 patients with cardiogenic shock were studied. The primary end point was the change of the cardiac index (CI) from baseline to 30 min after implantation. Secondary end points included lactic acidosis, hemolysis, and mortality after 30 days. RESULTS: In 25 patients the allocated device (n = 13 IABP, n = 12 Impella LP2.5) could be safely placed. One patient died before implantation. The CI after 30 min of support was significantly increased in patients with the Impella LP2.5 compared with patients with IABP (Impella: DeltaCI = 0.49 +/- 0.46 l/min/m(2); IABP: DeltaCI = 0.11 +/- 0.31 l/min/m(2); p = 0.02). Overall 30-day mortality was 46% in both groups. CONCLUSIONS: In patients presenting with cardiogenic shock caused by AMI, the use of a percutaneously placed LVAD (Impella LP 2.5) is feasible and safe, and provides superior hemodynamic support compared with standard treatment using an intra-aortic balloon pump. (Efficacy Study of LV Assist Device to Treat Patients With Cardiogenic Shock [ISAR-SHOCK]; NCT00417378).

Bivalirudin versus unfractionated heparin during percutaneous coronary intervention.

BACKGROUND: Whether bivalirudin is superior to unfractionated heparin in patients with stable or unstable angina who undergo percutaneous coronary intervention (PCI) after pretreatment with clopidogrel is unknown. METHODS: We enrolled 4570 patients with stable or unstable angina (with normal levels of troponin T and creatine kinase MB) who were undergoing PCI after pretreatment with a 600-mg dose of clopidogrel at least 2 hours before the procedure; 2289 patients were randomly assigned in a double-blind manner to receive bivalirudin, and 2281 to receive unfractionated heparin. The primary end point was the composite of death, myocardial infarction, urgent target-vessel revascularization due to myocardial ischemia within 30 days after randomization, or major bleeding during the index hospitalization (with a net clinical benefit defined as a reduction in the incidence of the end point). The secondary end point was the composite of death, myocardial infarction, or urgent target-vessel revascularization. RESULTS: The incidence of the primary end point was 8.3% (190 patients) in the bivalirudin group as compared with 8.7% (199 patients) in the unfractionated-heparin group (relative risk, 0.94; 95% confidence interval [CI], 0.77 to 1.15; P=0.57). The secondary end point occurred in 134 patients (5.9%) in the bivalirudin group and 115 patients (5.0%) in the unfractionated-heparin group (relative risk, 1.16; 95% CI, 0.91 to 1.49; P=0.23). The incidence of major bleeding was 3.1% (70 patients) in the bivalirudin group and 4.6% (104 patients) in the unfractionated-heparin group (relative risk, 0.66; 95% CI, 0.49 to 0.90; P=0.008). CONCLUSIONS: In patients with stable and unstable angina who underwent PCI after pretreatment with clopidogrel, bivalirudin did not provide a net clinical benefit (i.e., it did not reduce the incidence of the composite end point of death, myocardial infarction, urgent target-vessel revascularization, or major bleeding) as compared with unfractionated heparin, but it did significantly reduce the incidence of major bleeding. (ClinicalTrials.gov number, NCT00262054.)

Effect of abciximab on clinical and angiographic restenosis in patients with non-ST-segment elevation acute coronary syndromes.

The ISAR-REACT 2 trial was designed to assess the effect of abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after a 600-mg loading dose of clopidogrel. The aim of the present study was to investigate the impact of abciximab on clinical and angiographic restenosis after coronary stenting in patients with acute coronary syndromes. The angiographic substudy included 1,544 patients from the ISAR-REACT 2 trial randomly assigned to abciximab (771 patients) or placebo (773 patients). All patients were scheduled for routine angiographic follow-up at 6 to 8 months after intervention. The primary end point was incidence of angiographic in-segment binary restenosis. The secondary end point was 1-year incidence of target-lesion revascularization. Binary restenosis was observed in 21.9% of patients in the abciximab group and 24.5% of patients in the placebo group (p=0.29). Percentages of in-stent (29+/-22% vs 33+/-24%; p=0.02) and in-segment (35+/-20% vs 38+/-21%; p=0.04) diameter stenoses were significantly lower in the abciximab group than the placebo group. There was a strong trend toward lower 1-year incidence of target-lesion revascularization in patients treated with abciximab than in patients treated with placebo (13.6% vs 16.8%; p=0.08). In conclusion, in patients with non-ST-segment elevation acute coronary syndromes undergoing early percutaneous coronary intervention with stenting after a 600-mg loading dose of clopidogrel, abciximab therapy may have a slight positive impact on the prevention of restenosis.

Troponin level and efficacy of abciximab in patients with acute coronary syndromes undergoing early intervention after clopidogrel pretreatment.

OBJECTIVE: We investigated how does troponin level (TnT) affect the benefit achieved by abciximab in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) after pretreatment with a high loading dose of clopidogrel. METHODS: The Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT 2) trial included 2,022 patients with non-ST elevation ACS undergoing PCI who were randomized to abciximab or placebo after pretreatment with 600 mg of clopidogrel. The patients were divided into groups with elevated TnT level (n = 1,049) and no elevated TnT level (n = 973). The primary end point of the trial was the composite of death, myocardial infarction and urgent reintervention at 30 days. RESULTS: In patients with elevated TnT level the incidence of the primary end point was 13.1% in the abciximab group Vs. 18.3% in the placebo group [relative risk (RR): 0.70; 95% confidence interval (CI), 0.52-0.95, P = 0.02]. The combined incidence of death or myocardial infarction was 12.9% in the abciximab group vs. 17.9% in the placebo group (RR: 0.71; 95% CI, 0.52-0.96, P = 0.03). In contrast, the incidence of the primary end point in patients with no elevated TnT level was identical in both treatment groups (4.6%). The risk of bleeding was not related to TnT level. CONCLUSIONS: Baseline troponin level affects the benefit of abciximab in patients with ACS undergoing PCI after pretreatment with a high loading dose of clopidogrel. Abciximab reduces the risk of ischemic events only in patients with ACS and elevated troponin level.

One-year clinical outcomes with abciximab vs. placebo in patients with non-ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention after pre-treatment with clopidogrel: results of the ISAR-REACT 2 randomized trial.

AIMS: The aim of this study is to investigate whether the benefit of abciximab in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACSs) undergoing percutaneous coronary intervention (PCI) after pre-treatment with 600 mg clopidogrel is sustained at 1 year. METHODS AND RESULTS: We performed 1-year follow-up of 2022 high-risk patients with NSTE-ACS undergoing urgent PCI, who were randomized to abciximab or placebo after pre-treatment with 600 mg clopidogrel in the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 2 trial. The combined incidence of death, myocardial infarction, or target vessel revascularization at 1 year was the primary outcome analysis. At 1 year, the primary outcome was reached in 23.3% of patients allocated to abciximab vs. 28.0% of patients allocated to placebo [relative risk (RR) 0.80, 95% confidence interval (CI) 0.67-0.95, P = 0.012]. The combined incidence of death or myocardial infarction was 11.6% in patients allocated to abciximab vs. 15.3% in patients allocated to placebo (RR 0.74, 95% CI 0.59-0.94, P = 0.015). CONCLUSION: In high-risk patients with NSTE-ACS undergoing a PCI after pre-treatment with 600 mg clopidogrel, adverse events occurred less frequently with abciximab and the early benefit was maintained at 1 year after administration.

Sex and effect of abciximab in patients with acute coronary syndromes treated with percutaneous coronary interventions: results from Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 2 trial.

BACKGROUND: It is not known whether there exists a sex-dependent difference in the clinical benefit of abciximab in patients with acute coronary syndromes (ACS) undergoing a percutaneous coronary intervention (PCI). METHODS: We performed this retrospective analysis of 2022 patients (498 women) with ACS enrolled in the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 2 trial and randomized to receive abciximab or placebo during a PCI procedure. The incidence of major adverse cardiac events (MACE) during the 30 days after PCI was the primary end point of the study. RESULTS: Among men, the 30-day incidence of MACE was 8.6% in the abciximab group compared with 12.6% in the placebo group, relative risk (RR) 0.69 (95% confidence interval [CI] 0.50-0.94), P = .01. The 30-day incidence of MACE in women was 9.7% in the abciximab group compared with 9.9% in the placebo group, RR 0.98 (95% CI, 0.56-1.72), P = .97. After adjustment for baseline clinical and angiographic characteristics, there was no significant interaction between sex and abciximab (P = .71); adjusted RR was 0.70 (95% CI, 0.34-1.34) in women and 0.60 (95% CI, 0.40-0.90) in men. The incidence of major bleeding was significantly greater in women (3.6%) than in men (0.7%), RR 5.5 (95% CI, 2.54-11.9), P < .001, without any dependence on the form of therapy received. CONCLUSIONS: In patients with non-ST elevation ACS undergoing a PCI, the benefit with abciximab is greater in men than in women. This is apparently the result of sex-based differences in risk profile.

Age-dependent effect of abciximab in patients with acute coronary syndromes treated with percutaneous coronary interventions.

BACKGROUND: No studies have specifically performed an age-based analysis of the efficacy of abciximab in patients with non-ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention (PCI). The aim of the study was to assess whether there are age-dependent differences in the clinical benefit of abciximab in patients with acute coronary syndrome treated with PCI. METHODS AND RESULTS: We performed this retrospective analysis of 2022 patients with acute coronary syndrome enrolled in the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT 2) study and randomized to receive abciximab or placebo during a PCI procedure. The incidence of major adverse cardiac events (MACE) during the 30 days after PCI was the primary end point of the study. On the basis of the cutoff age value provided by logistic regression in connection with bootstrap resampling, patients were divided into those younger (n=1220) and older (n=802) than 70 years. Among younger patients, the incidence of MACE was 7.7% in the abciximab group versus 13.3% in the placebo group (relative risk 0.57, 95% confidence interval 0.40 to 0.80, P=0.001). In contrast, no difference was observed among older patients: The incidence of MACE was 10.9% in the abciximab group versus 9.9% in the placebo group (relative risk 1.10, 95% confidence interval 0.72 to 1.69, P=0.65). After adjustment for other variables, including cardiac troponin, there was a significant interaction between age and abciximab (P=0.04) with respect to MACE reduction, with abciximab being more effective in younger patients. CONCLUSIONS: In patients with non-ST-elevation acute coronary syndromes undergoing PCI, the efficacy of abciximab appears to be age-dependent, with greater benefit among younger patients.

Sustained increased risk of adverse cardiac events over 5 years after implantation of gold-coated coronary stents.

OBJECTIVE: To study the 5-year outcome of patients treated with gold-coated stent placement. BACKGROUND: We have previously shown in the setting of a randomized trial that gold-coated stents are associated with worse mid-term outcome, mainly because of an increased risk of restenosis, compared to uncoated stents. The long-term outcome and, in particular, mortality risk after implantation of gold-coated stents are not known. METHODS: A total of 731 patients with symptoms or signs of ischemia received randomly either a gold-coated (n = 367) or an uncoated steel stent (n = 364) of identical design. Patients were clinically followed-up at 1 and 5 years. The primary endpoint of the study was the composite of major cardiac events (death, myocardial infarction, or target vessel revascularization (TVR)). The incidence of death was a secondary endpoint. RESULTS: Five-year follow-up was available in 97.5% of the patients. The composite of death, myocardial infarction, or TVR occurred in 51% of the patients treated with gold-coated stents and 40% of the patients treated with uncoated stents (P = 0.005). Of note, there was a marked increase in the absolute difference in mortality between patients in the gold-coated and uncoated stent groups, from 1.6% at 1 year to 4.9% after 5-year follow-up (P = 0.09). A multivariate analysis showed that gold-coated stent implantation was independently associated with 5-year mortality (hazard ratio, 1.46; 95% confidence interval, 1.02-2.09; P = 0.04). CONCLUSIONS: Gold-coated stents are associated with a sustained increased overall risk for major cardiac events, and notably, they may increase the long-term mortality risk.

Abciximab and angiographic restenosis after coronary stent placement. Analysis of the angiographic substudy of ISAR-REACT--a double-blind, placebo-controlled, randomized trial evaluating abciximab in patients undergoing elective percutaneous coronary interventions after pretreatment with a high loading dose of clopidogrel.

BACKGROUND: ISAR-REACT was a trial designed to evaluate whether the glycoprotein IIb/IIIa inhibitor abciximab is beneficial in patients undergoing elective percutaneous coronary intervention (PCI) with stent placement after pretreatment with a 600 mg loading dose of clopidogrel. Objective for the angiographic substudy was to determine the impact of abciximab on angiographic restenosis after coronary stent placement. Previous analyses have suggested a reduction in the incidence of restenosis after the administration of abciximab. METHODS: The angiographic substudy comprises 1885 of 2159 patients enrolled in ISAR-REACT: 994 patients were randomly assigned to abciximab and 941 patients to placebo. All patients were scheduled for a routine angiographic follow-up after 6 months (performed in 80% of eligible patients). End points for the angiographic substudy were the rates of angiographic restenosis (> or = 50% diameter stenosis) and target lesion revascularization. RESULTS: The incidence of angiographic restenosis was 27% in the abciximab group and 29% in the placebo group (relative risk 0.92, 95% CI 0.79-1.06, P = .27). Late angiographic lumen loss was 0.95 +/- 0.68 and 0.99 +/- 0.70 mm, respectively (P = .25). Similar results were obtained in a subgroup analysis focusing on high-risk subsets. The rate of target lesion revascularization procedures was 22% in the abciximab group and 23% in the placebo group (relative risk 0.94, 95% CI 0.79-1.12, P = .52). CONCLUSIONS: In low- to intermediate-risk patients who undergo elective PCI after pretreatment with a high loading dose of clopidogrel >2 hours before PCI, the additional administration of the glycoprotein IIb/IIIa inhibitor abciximab is not associated with a significant reduction in angiographic restenosis.

Predictive factors of restenosis after coronary implantation of sirolimus- or paclitaxel-eluting stents.

BACKGROUND: The efficacy of drug-eluting stents in reducing restenosis risk has not been uniform across patient subsets. Identifying predictive factors of restenosis may help improve outcomes after percutaneous coronary interventions. METHODS AND RESULTS: All patients who underwent successful implantation of sirolimus- or paclitaxel-eluting stents in native vessels for de novo lesions between August 2002 and December 2004 were eligible for this study. All data were prospectively collected. Angiographic restenosis was defined as diameter stenosis > or =50% at follow-up in the in-segment area. Target lesion revascularization was defined as any revascularization procedure involving the target lesion. Included in this study were 1845 patients with 2093 target lesions. Multivariable analysis showed that vessel size, final diameter stenosis, and drug-eluting stent type were the strongest predictors of restenosis. A 0.5-mm decrease in vessel size was associated with adjusted odds ratios (ORs) of 1.74 (95% CI, 1.31 to 2.32) for angiographic restenosis and 1.65 (95% CI, 1.22 to 2.23) for target lesion revascularization. A 5% increase in final diameter stenosis was associated with adjusted ORs of 1.30 (95% CI, 1.15 to 1.47) for angiographic restenosis and 1.18 (95% CI, 1.03 to 1.35) for target lesion revascularization. Compared with paclitaxel-eluting stent, sirolimus-eluting stent was associated with adjusted ORs of 0.60 (95% CI, 0.44 to 0.81) for angiographic restenosis and 0.67 (95% CI, 0.49 to 0.91) for target lesion revascularization. CONCLUSIONS: Vessel size and drug-eluting stent type are the most important predictors of angiographic and clinical restenosis, with drug-eluting stent type having a particular impact on restenosis of small coronary vessels.

Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial.

CONTEXT: No specifically designed studies have addressed the role of the glycoprotein IIb/IIIa inhibitor abciximab in patients with non-ST-segment elevation acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) after pretreatment with 600 mg of clopidogrel. OBJECTIVE: To assess whether abciximab is associated with clinical benefit in high-risk patients with ACS undergoing PCI after pretreatment with 600 mg of clopidogrel. DESIGN, SETTING, AND PATIENTS: International, multicenter, randomized, double-blind, placebo-controlled study conducted from March 2003 through December 2005, enrolling 2022 patients (mean age, 66 years) with non-ST-segment elevation ACS undergoing PCI. INTERVENTIONS: Patients were assigned to receive either abciximab (0.25 mg/kg of body weight bolus, followed by a 0.125-microg/kg per minute [maximum, 10 microg/min] infusion for 12 hours, plus heparin, 70 U/kg of body weight) or placebo (placebo bolus and infusion of 12 hours, plus heparin bolus, 140 U/kg). All patients received clopidogrel, 600 mg, at least 2 hours prior to the procedure, as well as 500 mg of oral or intravenous aspirin. MAIN OUTCOME MEASURES: The primary end point was a composite of death, myocardial infarction, or urgent target vessel revascularization occurring within 30 days after randomization; secondary end points were rates of in-hospital major and minor bleeding. RESULTS: Of 2022 patients enrolled, 1012 were assigned to abciximab and 1010 to placebo. The primary end point was reached in 90 patients (8.9%) assigned to abciximab vs 120 patients (11.9%) assigned to placebo, a 25% reduction in risk with abciximab (relative risk [RR], 0.75; 95% CI, 0.58-0.97; P = .03). Among patients without an elevated troponin level, there was no difference in the incidence of primary end point events between the abciximab group (23/499 patients [4.6%]) and the placebo group (22/474 patients [4.6%]) (RR, 0.99; 95% CI, 0.56-1.76; P = .98), whereas among patients with an elevated troponin level, the incidence of events was significantly lower in the abciximab group (67/513 patients [13.1%]) compared with the placebo group (98/536 patients [18.3%]), which corresponds to an RR of 0.71 (95% CI, 0.54-0.95; P = .02) (P = .07 for interaction). There were no significant differences between the 2 groups regarding the risk of major and minor bleeding as well as need for transfusion. CONCLUSIONS: Abciximab reduces the risk of adverse events in patients with non-ST-segment elevation ACS undergoing PCI after pretreatment with 600 mg of clopidogrel. The benefits provided by abciximab appear to be confined to patients presenting with an elevated troponin level. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00133003.

Stem cell mobilization by granulocyte colony-stimulating factor in patients with acute myocardial infarction: a randomized controlled trial.

CONTEXT: Experimental studies and early phase clinical trials suggest that transplantation of blood-derived or bone marrow-derived stem cells may improve cardiac regeneration and neovascularization after acute myocardial infarction. Granulocyte colony-stimulating factor (G-CSF) induces mobilization of bone marrow stem cells. OBJECTIVE: To assess the value of stem cell mobilization by G-CSF therapy in patients with acute myocardial infarction. DESIGN, SETTING, AND PATIENTS: Randomized, double-blind, placebo-controlled trial of patients diagnosed with ST-segment elevation acute myocardial infarction who had successful reperfusion by percutaneous coronary intervention within 12 hours after onset of symptoms in Germany between February 24, 2004, and February 2, 2005. INTERVENTIONS: Patients were randomly assigned to receive subcutaneously either a daily dose of 10 microg/kg of G-CSF or placebo for 5 days. MAIN OUTCOME MEASURES: The primary end point was reduction of left ventricular infarct size according to technetium Tc 99m sestamibi scintigraphy performed at baseline and at 4 to 6 months after randomization. Secondary end points included improvement of left ventricular ejection fraction measured by magnetic resonance imaging and the incidence of angiographic restenosis. RESULTS: Of the 114 patients, 56 were assigned to receive treatment with G-CSF and 58 were assigned to receive placebo. Treatment with G-CSF produced a significant mobilization of stem cells. Between baseline and follow-up, left ventricular infarct size according to scintigraphy was reduced by a mean (SD) of 6.2% (9.1%) in the G-CSF group and 4.9% (8.9%) in the placebo group (P = .56) and left ventricular ejection fraction was improved by 0.5% (3.8%) in the G-CSF group and 2.0% (4.9%) in the placebo group (P = .14). Angiographic restenosis occurred in 19 (35.2%) of 54 patients in the G-CSF group and in 17 (30.9%) of 55 patients in the placebo group (P = .79). The most common adverse event among patients assigned to G-CSF was mild to moderate bone pain and muscle discomfort. CONCLUSION: Stem cell mobilization by G-CSF therapy in patients with acute myocardial infarction and successful mechanical reperfusion has no influence on infarct size, left ventricular function, or coronary restenosis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00126100.

Randomized trial of paclitaxel- and sirolimus-eluting stents in small coronary vessels.

AIMS: Sirolimus- and paclitaxel-eluting stents effectively reduce restenosis in small coronary vessels. The relative efficacy of these drug-eluting stents in this high-risk subset is not known. METHODS AND RESULTS: A total of 360 patients undergoing percutaneous coronary intervention for de novo lesions in native coronary vessels with a diameter of <2.80 mm received randomly paclitaxel-eluting stents (n=180) or sirolimus-eluting stents (n=180). The primary endpoint was in-stent late luminal loss. Secondary endpoints were angiographic restenosis and need of target lesion revascularization. The study intended to show that the paclitaxel-eluting stent is not inferior to the sirolimus-eluting stent with respect to the primary endpoint. The non-inferiority margin was set at 0.16 mm. Follow-up angiography was performed in 87% of the patients. In-stent late luminal loss in the paclitaxel-eluting stent group was 0.32 mm (upper 95% boundary, 0.42 mm), which was greater than that in the sirolimus-eluting stent group, failing to show the non-inferiority of the paclitaxel-eluting stent to the sirolimus-eluting stent (P>0.99). Angiographic restenosis was found in 19.0% of the lesions in the paclitaxel-eluting stent group and 11.4% of the lesions in the sirolimus-eluting stent group (P=0.047). Target lesion revascularization was performed in 14.7% of the lesions treated with paclitaxel-eluting stents and 6.6% of the lesions treated with sirolimus-eluting stents (P=0.008). CONCLUSION: The paclitaxel-eluting stent is associated with a greater late luminal loss and is less effective in reducing restenosis in small coronary vessels than the sirolimus-eluting stent.

Randomized trial of a nonpolymer-based rapamycin-eluting stent versus a polymer-based paclitaxel-eluting stent for the reduction of late lumen loss.

BACKGROUND: Although drug-eluting stents (DESs) constitute a major achievement in preventing restenosis, concerns remain regarding the increased inflammatory and thrombogenic responses associated with the polymers used. Recently, we showed that a nonpolymer on-site coating with rapamycin not only is feasible and safe but also leads to a dose-dependent reduction in restenosis. METHODS AND RESULTS: To assess whether polymer-free stents coated on-site with 2% rapamycin solution are inferior to polymer-based paclitaxel-eluting stents for the prevention of restenosis, we randomly assigned a total of 450 patients with de novo lesions in native coronary vessels, excluding the left main trunk, to either the polymer-free, rapamycin-coated Yukon DES (rapamycin stent) or the polymer-based, paclitaxel-eluting Taxus stent (paclitaxel stent). The primary end point was in-stent late lumen loss. Secondary end points were angiographic restenosis and target lesion revascularization. The study was designed to test the noninferiority of the rapamycin stent compared with the paclitaxel stent with respect to late lumen loss according to a noninferiority margin of 0.13 mm. Follow-up angiography was completed in 81% of the patients. The mean difference in in-stent late lumen loss between the rapamycin-stent group and the paclitaxel-stent group was 0.002 mm, and the upper limit of the 1-sided 95% confidence interval was 0.10 mm (P=0.02 from test for noninferiority). No significant differences were observed regarding angiographic restenosis rates (14.2% with the rapamycin stent and 15.5% with the paclitaxel stent) and target lesion revascularization rates due to restenosis (9.3% in both groups). CONCLUSIONS: The polymer-free, rapamycin-coated stent has an antirestenotic effect that is not inferior to that observed with the polymer-based paclitaxel-eluting stent.