比伐卢定对行经皮冠状动脉介入的急性冠状动脉综合征患者的作用:ACUITY试验的一项亚组分析

背景:评估对中危和高危的急性冠状动脉综合征患者,在行经皮冠状动脉介入时应用直接凝血酶抑制剂比伐卢定的抗凝效果。方法:ACUITY(急性导管术和急诊介入治疗筛选策略)试验中的13819例患者被前瞻性随机分配接受肝素(普通肝素或依诺肝素)联合糖蛋白IIb/IIIa拮抗剂、比伐卢定联合糖蛋白IIb/IIIa拮抗剂或单用比伐卢定治疗。其中7789例患者是在冠状动脉造影后行经皮冠状动脉介入治疗。在该亚组中评估上述3种治疗方案对30d主要终点即联合缺血事件(死亡、心肌梗死或因心肌缺血而行计划外血运重建)、严重出血和纯临床结局(联合缺血或严重出血)的影响。采用意向治疗分析。该试验在Clinical Trials.gov的注册号为NCT00093158。

急性ST段抬高心肌梗死患者经皮冠状动脉介入治疗时远端微循环保护的随机对照试验

Context: Atheromatous and thrombotic embolization during percutaneous coronary intervention (PCI) in acute myocardial infarction is common and may result in m icrocirculatory dysfunction, the prevention of which may improve reperfusion suc cess, reduce infarct size, and enhance event-free survival. Objective: To deter mine whether protection of the distal microcirculation from thromboembolic debri s liberated during primary PCI results in improved reperfusion and decreased inf arct size.Design, Setting, and Patients: Prospective randomized controlled trial at 38 academic and community-based institutionsin 7 countries enrolling 501 pa tients aged 18 years or older with ST-segment elevation myocardial infarction(S TEMI) presenting within 6 hours of symptom onset and undergoing primary PCI or r escue intervention after failed thrombolysis. Interventions: Patients were rando mized between May 20, 2002, and November 21, 2003, to receive PCI with a balloon occlusion and aspiration distal microcirculatory protection system vs angioplas ty without distal protection. Main Outcome Measures:Coprimary end points were ST -segment resolution(STR) measured 30 minutes after PCI by continuous Holter mon itoring and infarct size measured by technetium Tc 99m sestamibi imaging between days 5 and 14. Secondary end points included major adverse cardiac events. Resu lts: Among 252 patients assigned to distal protection, aspiration was performed in 97%(242/251), all angioplasty balloon inflations were fully protected in 79 %(193/245), and visible debris was retrieved from 73%(182/250). Complete STR w as achieved in a similar proportion reperfused with vs without distal protection (63.3%[152/240] vs 61.9%[148/239], respectively; absolute difference,1.4%[95 %confidence interval, -7.7%to 10.5%;P = .78]), and left ventricular infarct size was similar in both groups (median, 12.0%[n = 229] vs 9.5%[n = 208],respe ctively; P = .15). Major adverse cardiac events at 6 months occurred with simila r frequency in the distal protection and control groups (10.0%vs 11.0%, respec tively;P = .66). Conclusions: A distal balloon occlusion and aspiration system e ffectively retrieves embolic debris in most patients with acute STEMI undergoing emergent PCI.Nonetheless, distal embolic protection did not result in improved microvascularflow, greater reperfusion suc cess,reduced infarct size, or enhanced event-free survival.

急性ST段抬高的心肌梗死患者行经皮冠状动脉介入时对远端微循环的保护:一项随机对照试验

Context: Atheromatous and thrombotic embolization during percutaneous coronary intervention(PCI) in acute myocardial infarction is common and may result in microcirculatory dysfunction, the prevention of which may improve reperfusion success, reduce infarct size, and enhance event-free survival. Objective: To determine whether protection of the distal microcirculation from thromboembolic debris liberated during primary PCI results in improved reperfusion and decreased infarct size. Design, Setting, and Patients: Prospective randomized controlled trial at 38 academic and community-based institutions in 7 countries enrolling 501 patients aged 18 years or older with ST-segment elevation myocardial infarction(STEMI) presenting within 6 hours of symptom onset and undergoing primary PCI or rescue intervention after failed thrombolysis. Interventions: Patients were randomized between May 20, 2002, and November 21, 2003, to receive PCI with a balloon occlusion and aspiration distal microcirculatory protection systemvs angioplasty without distal protection. Main Outcome Measures: Coprimary end points were ST-segment resolution(STR) measured 30 minutes after PCI by continuous Holter monitoring and infarct size measured by technetium Tc 99m sestamibi imaging between days 5 and 14. Secondary end points included major adverse cardiac events. Results: Among 252 patients assigned to distal protection, aspiration was performed in 97%(242/251), all angioplasty balloon inflations were fully protected in 79%(193/245), and visible debris was retrieved from 73%(182/250). Complete STR was achieved in a similar proportion reperfused with vs without distal protection(63.3%[152/240] vs 61.9%[148/239], respectively; absolute difference, 1.4%[95%confidence interval,-7.7%to 10.5%; P=.78]), and left ventricular infarct size was similar in both groups(median, 12.0%[n=229] vs 9.5%[n=208], respectively; P=.15). Major adverse cardiac events at 6 months occurred with similar frequency in the distal protection and control groups(10.0%vs 11.0%, respectively; P=.66). Conclusions: A distal balloon occlusion and aspiration system effectively retrieves embolic debris in most patients with acute STEMI undergoing emergent PCI. Nonetheless, distal embolic protection did not resultin improved microvascularflow, greater reperfusion success, reduced infarct size, or enhanced event-free survival.

西罗莫司和紫杉醇洗脱冠状动脉支架的有效性和安全性

背景:最近关于药物洗脱支架增加支架血栓形成、心肌梗死和死亡风险的报道使其安全性受到质疑。但这些研究普遍存在样本量不足、采用历史对照、随访时间有限、无法获得原始资料等缺陷,不足以得出确定结论。方法:汇总分析资料包括:4项双盲试验,共有1748例患者随机分入西罗莫司洗脱支架组或裸金属支架组;5项双盲试验,共有3513例患者随机分入紫杉醇洗脱支架组或裸金属支架组。

治疗延迟对急性心肌梗死直接经皮冠状动脉介入治疗预后的影响:来自CADILLAC试验的分析

Background: The impact of treatment delays on outcomes after primary percutaneous coronary intervention for acute myocardial infarction is controversial. Methods: The CADILLAC trial randomized 2082 patients with acute myocardial infarction to stenting versus percutaneous transluminal coronary angioplasty, each with or without abciximab. Results: Earlier reperfusion(< 3 vs 3-6 vs >6 hours) was associated with lower 1-year mortality(2.6%vs 4.3%vs 4.8%, P=.046 for< 3 vs ≥3 hours), more frequent grade 2 to 3 myocardial blush(55%vs 53%vs 44%, P=.003), more frequent complete ST-segment resolution(64%vs 68%vs 47%, P=.006), and greater improvement in left ventricular function. Early reperfusion(< 3 vs 3-6 vs≥3 hours)was associated with lower mortality in high-risk patients(3.8%vs 6.9%vs 7.0%, P=.051 for< 3 vs ≥3 hours) but not in low-risk patients(1.4%vs 0.6%vs 1.0%, P=.63). Door-to-balloon times were independently correlated with mortality in patients presenting early after the onset of symptoms(≤2 hours, hazard ratio 1.24, P=.013) but not late(>2 hours, heart rate 0.88, P=.33). Conclusions: Early reperfusion results in superior clinical outcomes, enhanced microvascular reperfusion, and better recovery of left ventricular function. Incremental treatment delays impact mortality more in high-risk versus low-risk patients and more in patients presenting early versus late after the onset of symptoms. These data emphasize the importance of minimizing treatment delays and have implications regarding patient triage for primary percutaneous coronary intervention.

常规早期开始与延迟选择性应用糖蛋白IIb/IIIa抑制剂治疗急性冠状动脉综合征的比较:ACUITY时限试验

背景:对于接受早期介入治疗策略的中危和高危急性冠状动脉综合征(ACS)患者,当前的指南推荐在血管造影前对所有患者应用或推迟到血管成形术前在导管室内选择性应用血小板糖蛋白IIb/IIIa(GpIIb/IIIa)抑制剂治疗,但尚不清楚哪种方法更好。目的:确定对接受早期介入治疗策略的中危和高危A CS患者应用GpIIb/IIIa抑制剂的最佳策略。设计:前瞻性、随机、开放标记试验,有30d的临床随访期。机构:17个国家的450所基于学院和社区的机构。患者:共9207例拟接受早期介入治疗策略的中危和高危ACS患者。

ST段抬高型与非ST段抬高型急性心肌梗死患者行直接经皮冠状动脉介入术后早期及晚期预后(来自于CADILLAC试验)

We determined the outcomes of patients with acute ST-segment elevation(STE) myocardial infarction(STEMI) and non-STEMI(NSTEMI) after primary percutaneous coronary intervention(PCI). The prognosis after primary PCI in STEMI has been extensively studied and defined. Outcomes of patients who undergo primary PCI for NSTEMI are less well established. In total, 2,082 patients with ongoing chest pain for >30 minutes consistent with acute MI were randomized to balloon angioplasty versus stenting, each with/without abciximab. Of 1,964 patients, STEMI was present in 1,725(87.8%) and NSTEMI in 239(12.2%). Compared with STEMI, those with NSTEMI were more likely to have delayed time-to-hospital arrival(2.4 vs 1.8 hours, p=0.0002) and increased door-to-balloon time(3.2 vs 1.9 hours, p< 0.0001). Patients with NSTEMI were more likely to have Thrombolysis In Myocardial Infarction grade 3 flow at baseline(37.3%vs 19.4%, p< 0.0001) and higher ejection fraction(58.7%vs 55.8%, p=0.001), but similar rates of postprocedural Thrombolysis In Myocardial Infarction grade 3 flow. At 1 year, patients with NTEMI had similar mortality(3.4%vs 4.4%, p=0.40) but higher rates of major adverse cardiac events(24.0%vs 16.6%, p=0.007) that was driven by more frequent ischemic target vessel revascularization(21.8%vs 11.9%, p< 0.0001). In conclusion, patients with acute MI without STE who are treated with primary PCI have marked delays to treatment, similar late mortality, and increased rates of ischemic target vessel revascularization compared with patients with STEMI, despite more favorable angiographic features at presentation and similar reperfusion success. The adverse prognosis of patients with NSTEMI should be recognized and efforts made to decrease reperfusion times.

老年急性心肌梗死患者首次行冠状动脉介入治疗的预后:降低晚期血管成形术并发症的阿昔单抗和设备的调查试验(CADILLAC)

Background-Biological age is a strong determinant of prognosis in patients with acute myocardial infarction(AMI). We sought to examine the impact of age after primary percutaneous coronary intervention in AMI and to determine whether routine coronary stent implantation and/or platelet glycoprotein IIb/IIIa inhibitors improve clinical outcomes in elderly patients after primary angioplasty. Methods and Results-In the CADILLAC trial, 2082 patients with AMI were randomized to balloon angioplasty,angioplasty plus abciximab,stenting alone, or stenting plus abciximab. No patient was excluded on the basis of advanced age; patients ranging from 21 to 95 years of age were enrolled. One-year mortality increased for each decile of age, exponentially after 65 years of age(1.6%for patients< 55 years, 2.1%for 55 to 65 years, 7.1%for 65 to 75 years, 11.1%for patients >75 years; P< 0.0001). Elderly patients also had increased rates of stroke and major bleeding compared with their younger counterparts. Among elderly patients (≥65 years), 1-year rates of ischemic target revascularization (7.0%versus 17.6%; P< 0.0001) and subacute or late thrombosis (0%versus 2.2%; P=0.005)were reducedwith stenting comparedwith balloon angioplasty. Routine abciximab administration, although safe,was not of definite benefit in elderly patients. Rates of mortality, reinfarction, disabling stroke, and major bleeding in the elderly were independent of reperfusion modality. Conclusions-Despite contemporary mechanical reperfusion strategies,mortality, major bleeding, and stroke rates remain high in elderly patients undergoing primary percutaneous coronary intervention, outcomes that are not affected by stents or glycoprotein Ⅱb/Ⅲa inhibitors. By reducing restenosis, however, stent implantation improves clinical outcomes in elderly patients with AMI.

以血小板糖蛋白IIb/IIIa受体抑制作为隐静脉桥支架置入术的辅助治疗:随机分配接受血管阻塞或滤网血栓保护后的不同疗效

Aims: Although embolic protection devices reduce complications during saphenous vein graft(SVG) stenting, adverse events still occur in ～10%of patients. IIb/IIIa antagonists have not been proven effective during SVG intervention. We hypothesized that adjunctive use of these agents might enhance the efficacy of embolic protection devices. Methods and results: In the prospective, multicentre FilterWire EX Randomized Evaluation trial, 651 patients undergoing SVG stenting were randomized to either filter-based FilterWire EX or balloon occlusion/aspiration GuardWire embolic protection devices. IIb/IIIa inhibitor use was at the discretion of the investigator, with randomization stratified by intended use. Patients pre-selected for IIb/IIIa inhibitor use(n=345) had higher baseline risk, with increased 30-day major adverse cardiac events(MACE, 13.0 vs. 8.0%, P=0.03). GuardWire assigned patients treated with IIb/IIIa inhibitors had higher 30-day MACE compared with those not treated with IIb/IIIa inhibitors(16.0 vs. 6.3%, P=0.007). In contrast, MACE in high-risk FilterWire patients treated with IIb/IIIa inhibitors were similar to their lower risk, untreated counterparts(9.9 vs. 9.5%, P=0.89). Multivariable analysis detected a borderline significant(P=0.056) interaction for lower MACE between FilterWire and IIb/ IIIa inhibitor use. Adjustment by the propensity to use IIb/IIIa inhibitors resulted in a significant(P=0.023) interaction for lower MACE rates. IIb/IIIa inhibition in conjunction with FilterWire was associated with less abrupt closure, no reflow, or distal embolization. Conclusion: IIb/IIIa antagonists may improve procedural outcome during SVG stenting in high risk patients, utilizing filter-based embolic protection devices.

手术成功与临床危险状态在决定急性心肌梗死患者早期血管成形术后能否出院时的作用

We evaluated whether patients’clinical status, angioplasty success, or both, should guide discharge after primary angioplasty(i.e., percutaneous coronary intervention ) for acute myocardial infarction(AMI). Current guidelines do not address a discharge strategy for AMI patients undergoing successful PCI. Patients who underwent PCI in Primary Angioplasty in Myocardial Infarction (PAMI) studies(N=3,188)were classified as "high clinical risk"if they had either age >70 years, Killip class >1, heart rate >100 beats/min, systolic blood pressure< 100 mm Hg, anterior MI, or left bundle branch block, and as "low clinical risk"if none was present. Successful PCI patients were compared with those with unsuccessful PCI in both groups for 30-day major adverse cardiac events (MACE). Percutaneous coronary intervention was successful in 668(90%) of 745 lowrisk clinicaland 2,104 (86%) of 2,443 high-risk clinical patients. Regardless of clinical risk status, patients with successful PCI had lower 30-day MACE than those with unsuccessful PCI (low-risk group: 4.6%vs. 22%, p< 0.0001; high-risk group: 7%vs. 21%; p< 0.0001). Moreover, successful PCI patients with either risk status had few MACE after day 4, whereas unsuccessful PCI patients had more MACE. The success of PCI was the strongest independent predictor of 30-day MACE(odds ratio3.7, 95%confidence interval2.8 to 5.0). A constellation of three or more high-risk clinical features also predicted higher 30-dayMACE (OR2.25, 95%CI 1.62 to 3.12). The success of PCI is the prime determinant of clinical outcome after PCI for AMI. The majority of AMI patients with less than three high-risk clinical features who undergo successful PCI may be discharged from the hospital by day 4. In contrast, patients with more than two high-risk clinical features or unsuccessful PCI may need longer observation.

紫杉醇药物洗脱支架用于经皮冠状动脉血运重建的成本效益分析:TAXUS-IV临床试验的结果

Objectives: This study sought to compare aggregate medical care costs for patients undergoing percutaneous coronary intervention with paclitaxel-eluting stents(PES) and bare-metal stents(BMS) and to formally evaluate the incremental cost effectiveness of PES for patients undergoing single-vessel percutaneous coronary intervention. Background: Although the cost effectiveness of SES has been studied in both clinical trials and decision-analytic models, few data exist on the cost effectiveness of alternative drug-eluting stent(DES) designs. In addition, no clinical trials have specifically examined the cost effectiveness of DES among patients managed without mandatory angiographic follow-up. Methods: We performed a prospective economic evaluation among 1,314 patients undergoing percutaneous coronary revascularization randomized to either PES(N=662) or BMS(N=652) in the TAXUS-IV trial. Clinical outcomes, resource use, and costs(from a societal perspective) were assessed prospectively for all patients over a 1-year follow-up period. Cost effectiveness was defined as the incremental cost per target vessel revascularization(TVR) event avoided and was analyzed separately among cohorts assigned to mandatory angiographic follow-up(n=732) or clinical follow-up alone(n=582). Results: The PES reduced TVR by 12.2 events per 100 patients treated, resulting in a 1-year cost difference of ＄572 per patient with incremental cost-effectiveness ratios of ＄4,678 per TVR avoided and ＄47,798/quality-adjusted life year(QALY) gained. Among patients assigned to clinical follow-up alone, the net 1-year cost difference was ＄97 per patient with cost-effectiveness ratios of ＄760 per TVR event avoided and ＄5,105/QALY gained. Conclusions: In the TAXUS-IV trial, treatment with PES led to substantial reductions in the need for repeat revascularization while increasing 1-year costs only modestly. The cost-effectiveness ratio for PES in the study population compares reasonably with that for other treatments that reduce coronary restenosis, including alternative drug-eluting stent platforms.