急性心肌梗死患者直接经皮冠状动脉介入术后院内死亡的预测因素

目的分析急性心肌梗死(AMI)患者直接PCI术后发生院内死亡的预测因素,以寻找进一步改善AMI患者住院期间预后的可能途径。方法根据314例接受直接PCI的AMI患者住院期间存活与否,将其分为死亡组(26例)和非死亡组(288例),比较两组患者的临床和冠状动脉造影特点,确定发生院内死亡的预测因素。结果死亡组患者中女性(P=0.017)、年龄>75岁(P=0.004)、3支血管病变(P=0.015)、左主干闭塞(P=0.036)、就诊至球囊扩张时间>90min(P=0.013)、并发心源性休克(P=0.000)显著高于非死亡组患者;而PCI成功(P=0.000)、ST段下降>50%(P=0.000)显著低于非死亡组患者。多因素分析显示,心源性休克(P=0.000)、女性(P=0.029)、就诊至球囊扩张时间>90min(P=0.035)是发生院内死亡的独立预测因素。结论为进一步改善接受直接PCI的AMI患者住院期间的预后,未来治疗的重点在于降低高危(特别是心源性休克)患者的病死率,缩短就诊至球囊扩张时间,以及改善冠状动脉微循环和提高心肌水平的再灌注。     

Combination platelet glycoprotein IIb/IIIa receptor and lepirudin administration during percutaneous coronary intervention in patients with heparin-induced thrombocytopenia.

We evaluated a combination therapy using glycoprotein IIb/IIIa receptor antagonism and direct thrombin inhibition in nine patients with heparin-induced thrombocytopenia (HIT) undergoing 10 percutaneous coronary interventions (PCIs). In selected patients with HIT, the combination of a direct thrombin inhibitor, lepirudin, and abciximab, tirofiban, or eptifibatide appears to be a safe and effective anticoagulation strategy for PCI.     

Effectiveness and safety of glycoprotein IIb/IIIa inhibitors in patients with myocardial infarction undergoing primary percutaneous coronary intervention: a meta-analysis of observational studies

Introduction

Meta-analyses of randomized controlled trials (RCT) showed that glycoprotein IIb/IIIa inhibitors (GPI) are associated with reduced adverse events following primary percutaneous coronary revascularization (PCI). However, the external validity of RCTs is generally limited due to their restricted inclusion of patients. The objective of this study is to evaluate the effectiveness and safety of GPI, as adjuvant therapy for primary PCI in real-life patients with myocardial infarction with ST segment elevation (STEMI) from the general population.

Methods

We identified all published peer-reviewed observational studies enrolling STEMI patients who underwent primary PCI. We performed random-effect meta-analyses to determine the association of GPI with major adverse events.

Results

A total of 11 studies, enrolling 12,253 patients, were retained for this meta-analysis. GPI was associated with approximately 53% reduction in short-term mortality (odds ratio (OR): 0.47, 95% confidence intervals (CI): 0.32-0.68). There was a 62% reduction in long-term mortality associated with GPI (OR: 0.38, 95% CI: 0.30-0.50). GPI was associated with a 62% reduction in 30-day re-infarction (OR: 0.38, 95% CI: 0.24-0.60) and 42% reduction in 30-day repeat PCI (OR: 0.58, 95% CI: 0.36-0.94). A non-significant increase in major bleeding with GPI was observed with an OR of 1.55 (95% CI: 0.92-2.62).

Conclusions

GPI is associated with significant reductions in short-term mortality, re-infarction and repeat PCI, long-term mortality and an inconclusive increase in major bleeding. These results provide evidence for the safety and effectiveness of GPI as adjuvant therapy for primary PCI in real-life STEMI patients.     

Platelet glycoprotein IIb/IIIa receptor blockade and coronary resistance in unstable angina

OBJECTIVES: We designed a study to explore the effect of glycoprotein (GP) IIb/IIIa blockade on the atherosclerotic plaque and distal coronary vasculature. BACKGROUND: Platelet GP IIb/IIIa blockers have been proven to be beneficial in acute ischemic syndromes. This effect has also been attributed to the prevention of microvascular obstruction, although the underlying mechanisms have not been fully defined. METHODS: Eighteen patients with unstable refractory angina pectoris underwent cardiac catheterization and angioplasty. Trans-stenotic and microvascular resistances to flow were measured at baseline, during hyperventilation, and after intracoronary adenosine. Measurements were repeated early after abciximab administration and after successful percutaneous transluminal coronary angioplasty. RESULTS: Hyperventilation induced an ischemic attack in 12 of 18 patients and increased epicardial (12.8 +/- 16.9 vs. 6.1 +/- 6.1 mm Hg/ml per min, p < 0.05) and microvascular (9.9 +/- 7.5 vs. 6.8 +/- 5.8 mm Hg/ml per min, p < 0.05) coronary resistance. Abciximab had no significant effect on epicardial resistance, although it significantly reduced distal coronary resistance under all study conditions, including baseline (4.8 +/- 4.8 mm Hg/ml per min, p < 0.01), hyperventilation (5.1 +/- 5.4 mm Hg/ml per min, p < 0.01), and intracoronary adenosine (2.7 +/- 3.0 vs. 4.3 +/- 4.3 mm Hg/ml per min, p < 0.05). The hyperventilation test became negative in all patients after abciximab administration. CONCLUSIONS: These observations confirm the immediate beneficial effects of platelet GP IIb/IIIa blockade with abciximab in acute ischemic syndromes and suggest that improvement of microvascular function may play a central role in the mechanism of action of this drug.     

盐酸替罗非班在急性心肌梗死患者急诊冠状动脉介入治疗中的有效性和安全性评价

目的:评价血小板膜糖蛋白Ⅱb/Ⅲa受体拮抗剂盐酸替罗非班在急性心肌梗死(AMI)患者急诊冠状动脉介入治疗(PCI)中的有效性和安全性。方法:将106例AMI患者随机分为替罗非班组(替罗非班+直接PCI,55例)和对照组(直接PCI,51例)。比较2组患者梗死相关动脉PCI后即刻TIMI血流,术后90 min心电图ST段回落百分比(sumSTR),术后6 h、12 h肌酸激酶同工酶变化,术后1周左室射血分数,术后30 d内不良心脏事件(心绞痛、心肌梗死、死亡)及出血和血小板减少的发生率。结果:2组基础临床情况和冠状动脉造影特征无明显差异。替罗非班组梗死相关动脉PCI术后即刻TIMI血流、术后90 min sumSTR均显著高于对照组;术后30 d内不良心脏事件明显少于对照组;术后6 h、12 h肌酸激酶同工酶变化、术后1周左室射血分数与对照组相比差异无统计学意义。替罗非班组轻度出血发生率高于对照组,但未发生严重出血和血小板减少症。结论:替罗非班能明显降低AMI患者PCI后缺血事件的发生,在急诊PCI中是有效而安全的。     

直接PCI治疗高龄急性ST段抬高性心肌梗死

目的评价高龄急性ST段抬高性心肌梗死（ST-segment elevation myocardial infarction,STEMI）患者行直接经皮冠状动脉介入（percutaneous coronary intervention,PCI）治疗的安全性和有效性。方法对比分析46例高龄STEMI患者（高龄组）和64例年轻STEMI患者（年轻组）冠状动脉造影特征、直接PCI治疗的情况．即刻手术成功率、住院及随访期间主要心血管事件的发生情况。结果高龄组与年轻组比较,冠状动脉病变多为多支病变（73．9％比28．1％,P〈0．01）;2组手术即刻成功率无明显差异;2组术后达到心肌梗塞溶栓（thrombolysis inmyoxardial infarction,TIMI）3级血流患者比率无明显差异;高龄组手术操作时间较年轻组长[（64．4±25．4）min比（49．7±21．8）min,P〈0．05];高龄组住院期间、随访期间累计总的主要心血管事件发生率明显高于年轻组。随访期间,高龄组1例术后4个月猝死,死亡原因不明,1例术后1年死于脑出血：年轻组无死亡病例。结论对高龄STEMI患者行直接PCI治疗是比较安全而有效的再灌注手段。     

Coronary perforation during percutaneous coronary intervention in the era of abciximab platelet glycoprotein IIb/IIIa blockade: an algorithm for percutaneous management.

Coronary perforation is an uncommon but potentially life-threatening complication of percutaneous coronary intervention. The use of both atheroablative technologies for coronary intervention and adjunctive platelet glycoprotein blockade pharmacology may increase the incidence of or risk for life-threatening bleeding complications following the occurrence of coronary artery perforation. The interventional database for 6,214 percutaneous coronary interventions performed between January 1995 and June 1999 was analyzed. Hospital charts and cine angiograms for all patients identified in the database as having had coronary perforation were reviewed. Coronary perforation complicated 0.58% of all procedures and was more commonly observed in patients with a history of congestive heart failure and following use of atheroablative interventional technologies (2.8%). There was no association of abciximab therapy with either the incidence of or classification for coronary perforation. Adverse clinical outcomes (death, emergency surgical exploration) were related to the angiographic classification of perforation and were more frequently observed in patients who experienced a class 3 coronary perforation. These data suggest that specific clinical and procedural demographic factors are associated with the occurrence and severity of angiographic coronary perforation. An angiographic perforation class-specific algorithm for treatment of coronary perforation is proposed.     

Efficacy and safety of argatroban with or without glycoprotein IIb/IIIa inhibitor in patients with heparin induced thrombocytopenia undergoing percutaneous coronary intervention for acute coronary syndrome

Background There is limited experience with the use of argatroban in combination with glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitor in acute coronary syndrome (ACS) patients with heparin-induced thrombocytopenia (HIT) undergoing percutaneous coronary intervention (PCI). Materials and methods This single-center, retrospective study evaluated the efficacy (composite of death, myocardial infarction, or urgent revascularization) and safety (evaluated by TIMI major bleeding) of the argatroban with or without a GPIIb/IIIa inhibitor during PCI. Among 102 consecutive ACS patients (71.6% unstable angina or NSTEMI and 28.4% STEMI) who received argatroban (239 ± 104 μg/kg bolus, followed by a 17 ± 11 μg/kg/min infusion) for confirmed or suspected HIT during PCI, 52 patients (51%) received a GPIIb/IIIa inhibitor simultaneously (86% integrilin, 10% tirofiban, 4% abciximab) and 50 patients (49%) did not. Results There was no difference between the groups in the efficacy endpoint, which occurred in nine patients (17.3%) who received GPIIb/IIIa inhibitor and in eight patients (16%) who did not (P = 0.70). TIMI major bleeding occurred in three (5.8%) patients in the GPIIa/IIIb inhibitor group versus 0 (0%) patients in the argatroban alone group (P = 0.085). Conclusion In patients with suspected or confirmed HIT undergoing PCI for ACS, argatroban with or without GPIIb/IIIa appears to provide adequate anticoagulation and is well tolerated with a low rate of bleeding.     

In-hospital mortality among women undergoing contemporary elective percutaneous coronary intervention: a reexamination of the gender gap

BACKGROUND: Previous studies have indicated that, compared with men, women are at increased risk for in-hospital mortality following percutaneous coronary intervention (PCI); however, angioplasty techniques and mortality rates have improved since earlier reports. HYPOTHESIS: We sought to reevaluate and explore further the relationship between gender and angioplasty outcomes in contemporary "real world" practice. METHODS: The influence of gender and other covariates on in-hospital mortality and other adverse events among all patients who underwent elective coronary angioplasty in New York State from 1999 to 2001 (n = 106,262) was examined. RESULTS: In-hospital mortality rates for elective angioplasty were low; however, women demonstrated a two-fold mortality excess compared with men (0.6 vs. 0.3%, p < 0.0001). Women were older and more likely than men to demonstrate certain higher-risk features (heart failure, class III-IV angina, renal failure, vascular disease); however, men were more likely to have depressed ejection fraction, prior myocardial infarction, and prior coronary revascularization. Using multivariate analysis adjusting for clinical risk factors, gender remained an independent predictor of in-hospital mortality at all ages. Women were also more likely to experience nonfatal adverse events following PCI, including more frequent need for emergency bypass surgery. CONCLUSIONS: Despite improvements in angioplasty outcomes with time, women remain at significantly higher risk of in-hospital death than men after elective PCI. This increased mortality is observed in every age group, even after adjusting for other significant comorbidities.     

直接PCI治疗高龄急性ST段抬高性心肌梗死

目的 评价高龄急性ST段抬高性心肌梗死(ST-segment elevation myocardial infarction,STEMI)患者行直接经皮冠状动脉介入(pereutaneous coronary intervention.PCI)治疗的安全性和有效性.方法 对比分析46例高龄STEMI患者(高龄组)和64例年轻STEMI患者(年轻组)冠状动脉造影特征、直接PCI治疗的情况,即刻手术成功率、住院及随访期间主要心血管事件的发生情况.结果 高龄组与年轻组比较,冠状动脉病变多为多支病变(73.9%比28.1%,P<0.01);2组手术即刻成功率无明显差异;2组术后达到心肌梗塞溶栓(thmmbolysis in myoxardial infarction,TIMI)3级血流患者比率无明显差异;高龄组手术操作时间较年轻组长[(64.4±25.4)min比(49.7±21.8)min,P<0.05];高龄组住院期间、随访期间累计总的主要心血管事件发生率明显高于年轻组.随访期间,高龄组1例术后4个月猝死,死亡原因不明,1例术后1年死于脑出血;年轻组无死亡病例.结论 对高龄STEMI患者行直接PCI治疗是比较安全而有效的再灌注手段.     

不同剂量替格瑞洛在老年急性心肌梗死病人PCI术后抗血小板治疗中的有效性与安全性

目的比较低剂量替格瑞洛(180 mg负荷量,续贯60 mg每日2次口服)与标准剂量替格瑞洛(180 mg负荷量,续贯90 mg每日2次口服)在老年急性心肌梗死(AMI)病人经皮冠状动脉介入术(PCI)术后抗PLT治疗中的有效性与安全性。方法研究共入选196例成功接受PCI治疗的老年AMI病人,随机分为低剂量替格瑞洛组和标准剂量替格瑞洛组,详细记录病人住院期间及随访1年的主要不良心脑血管事件(MACCE)与出血事件。结果低剂量替格瑞洛组住院期间及随访至1年MACCE发生率与标准剂量替格瑞洛组相比,差异无统计学意义。住院期间2组小出血(8.4%比18.6%,P=0.061)和大出血发生率(1.1%比2.9%,P=0.622)差异无统计学意义;低剂量替格瑞洛组随访1年小出血发生率显著低于标准剂量替格瑞洛组(16.8%比36.9%,P=0.002),大出血方面2组差异无统计学意义(1.1%比3.9%,P=0.371)。Kaplan-Meier生存分析显示,低剂量替格瑞洛组1年无MACCE生存率与标准剂量替格瑞洛组相比,差异无统计学意义(P=0.823)。结论AMI病人PCI术后接受小剂量替格瑞洛较常规剂量相比,不增加MACCE事件发生率,同时可降低小出血风险。     

高龄急性心肌梗死患者经皮冠状动脉介入治疗效果及安全性分析

目的：评价高龄急性心肌梗死患者行冠状动脉介入治疗（PCI）的安全性和有效性。方法回顾性地分析西安交通大学医学院第一附属医院近5年来高龄（≥80岁）急性心肌梗死病例78例。其中PCI治疗40例,药物保守治疗38例,对比分析两组患者的基础临床资料、住院期间临床疗效以及PCI术后6个月的随访结果。结果与药物保守治疗组相比,PCI治疗组住院期间心肌梗死症状缓解率明显提高（52.63%vs 75.00%,P＜0.05）,心力衰竭发生率明显降低（39.47%vs 15.00%,P＜0.05）。出院后6个月内再次心绞痛（42.86%vs 18.42%）和心肌梗死（22.86%vs 5.26%）的发生率均显著降低（P＜0.05）,再次心血管事件和猝死的发生率也有一定下降（25.71%vs 10.52%,P＝0.09）。结论 PCI治疗可以改善高龄急性心肌梗死患者的临床症状和预后,从而进一步提高患者生存质量。由此可见,高龄急性心肌梗死患者的 PCI治疗是安全可行和有效的。     

那屈肝素在冠状动脉介入治疗中的效果和安全性

目的探讨那屈肝素在经皮冠状动脉介入治疗（PCI）中应用的有效性和安全性。方法将我院2005年5月至2006年1月收治的共172例行PCI术的患者分为2组。A组为PCI术中用那屈肝素（0.1 ml/10 kg）,B组为PCI术中用普通肝素（133μkat,1μkat=60 u）。A组87（男62,女25）例,年龄（63±3）岁。B组85（男71,女14）例,年龄（62±2）岁。PCI前静脉注射那屈肝素或普通肝素。A组和B组又分别分为择期和急诊PCI。出血程度的判断根据TIMI研究的标准进行。观察所有患者的心脏事件（死亡、再梗死、血运重建）。结果两组的一般临床资料比较差异无显著性。A组与B组手术成功率（100%vs100%）;30 d内主要心血管不良事件比较两组差异均无显著性;在轻微出血方面那屈肝素显著低于普通肝素组（P<0.05）。结论那屈肝素在急性心肌梗死患者行PCI术中的应用是有效的、安全的。     

氯吡格雷在经皮冠状动脉介入治疗中的应用

目的探讨氯吡格雷在经皮冠状动脉介入治疗(PCI)中的应用及疗效。方法选择91例行经皮腔内冠状动脉成形术(PTCA)+支架术的患者,分为两组:A组(26例应用氯吡格雷)和B组(65例应用噻氯匹定),对比观察其抗血小板聚集作用(监测凝血指标),随访有无心血管事件并观察药物不良反应。结果两组比较,氯吡格雷和噻氯匹定的抗血小板聚集疗效和随访的心血管事件无显著差异(P>0.05),A组不良反应总发生率低于B组(P=0.008)。结论氯吡格雷在PCI中的应用是安全有效的。     

补救性经皮冠状动脉腔内成形术治疗急性心肌梗塞

目的探讨补救性经皮冠状动脉腔内成形术（ＰＴＣＡ）在治疗急性心肌梗塞（ＡＭＩ）中的作用。方法对溶栓治疗失败的３６例患者进行补救性ＰＴＣＡ治疗。患者心功能Ｋｉｌｐ分级：Ⅲ级和Ⅳ级４例，Ⅱ级和Ⅰ级３２例。冠状动脉造影显示梗塞相关动脉：前降支１７例，右冠状动脉１４例，回旋支４例，中间动脉１例。ＰＴＣＡ前ＴＩＭＩⅠ级和Ⅰ～Ⅱ级血流各２例，余３２例均为ＴＩＭＩ０级。３６例均进行ＰＴＣＡ治疗，其中１３例患者置入了支架。结果术中除３例失败外，３１例患者病变血管血流达到ＴＩＭＩⅢ级，２例ＴＩＭＩⅡⅢ级，残余狭窄≤５０％，成功率为９１．７％。院内并发症：１例在ＰＴＣＡ成功后当天因顽固性休克和心室纤颤死亡；１例于第３天死于心脏破裂，住院病死率为５．６％。１４例患者在术后１～２个月内复查冠状动脉造影，２例发生再狭窄。结论ＡＭＩ患者在溶栓治疗失败后，在有条件的医院可施行补救性ＰＴＣＡ治疗，成功率高，对改善患者的近期和远期预后可能有利     

高龄急性心肌梗死患者直接PCI治疗的安全性及近期疗效分析

目的探讨高龄(75岁以上)急性心肌梗死(AMI)患者行直接冠状动脉介入治疗(PCI)的安全性及住院期间的预后。方法将连续247名接受直接PCI治疗的ST段抬高的AMI患者分为3组:≥75岁为高龄组(研究组,63例),65～74岁(老年组,80例)及<65岁(低龄组,104例)患者为对照组,比较高龄组及两个对照组患者接受直接PCI治疗的安全性及住院期间的预后。结果高龄组患者的外周血管严重病变、冠状动脉多支病变及钙化弥漫性病变多于两个对照组,但三组PCI治疗的成功率相当(分别为90.5%、93.8%和95.2%,P>0.05);高龄组患者PCI后24h内肾功能恶化的发生率显著高于对照组;高龄组患者住院期间严重心血管事件(死亡、再梗死)的发生率较高(分别为12.7%、7.5%、2.9%,P=0.02)。大出血发生率差异无统计学意义。结论ST段抬高的高龄AMI患者直接行PCI治疗安全可行;但近期疗效略逊于低龄患者。     

Same-day transradial outpatient stenting with a 6-hr course of glycoprotein IIb/IIIa receptor blockade: a feasibility study.

The aim of the study was to explore the feasibility of same-day outpatient stent placement using a short course of intravenous antiplatelet therapy. Patients (n = 26) had stent placement and 6 hr of eptifibatide therapy. Demographics, procedural information, CPK data, and length of stay were recorded along with postdischarge outcomes. Twenty-one men and five women with median age of 60 years (49, 69) underwent transradial stenting. Baseline characteristics included diabetes 62%, hyperlipidemia 77%, prior coronary bypass surgery 19%, and unstable angina 35%. There were no CPK elevations (> 2 x normal) or ECG changes. Discharge occurred after 6.5 hr (5.8, 7.0). Neither vascular site complications nor readmission for procedure-related problems occurred. One patient later expressed concerns about discharge education. Outpatient stent placement with 6-hr infusion of GP IIb/IIIa inhibitor appears feasible and efficient in select patients. There may be challenges to meet with regard to patient education. Further studies with larger populations are needed to evaluate and optimize this approach.     

Oral platelet glycoprotein IIb/IIIa receptor inhibitors--Part I

With the central importance of antiplatelet therapy in patients with coronary artery disease and the numerous positive trials with glycoprotein (GP) IIb/IIa inhibitors given intravenously, it was hoped that one could extend the benefit of IIb/IIIa inhibition to long-term treatment. Although the hypothesis that prolonged oral IIb/IIIa inhibition was appealing, many issues have been identified in the initial Phase II trials that would limit the usefulness of these compounds. Variability of the level of platelet inhibition was one major culprit that distinguished the oral compounds from intravenous ones. The problems that arose were that increased bleeding has been seen when levels of platelet inhibition are high (e.g., > 90%) and that, conversely, efficacy would likely be limited when levels of platelet inhibition were low. If further development of this class of drugs is undertaken, formal dosing studies would have to establish an oral dosing strategy that achieves appropriately high (80-95% inhibition) and steady levels of inhibition.     

低剂量替罗非班在老年急性ST段抬高心肌梗死急诊冠脉介入治疗中的应用

目的探讨低剂量替罗非班在老年急性ST段抬高心肌梗死(STEMI)患者(≥75岁)急诊经皮冠脉介入(PCI)治疗中应用的疗效及安全性。方法前瞻性入选2009年3月至2013年3月因STEMI行急诊PCI的老年患者172例,随机分为标准剂量组、低剂量组及对照组。标准剂量组术前给予替罗非班10μg/kg在3 min内静脉推注,然后以0.10~0.15μg/(kg·min)静脉滴注维持48 h。低剂量组术前给予负荷量(5μg/kg)在3 min内静脉推注后以0.05~0.075μg/(kg·min)静脉滴注维持24 h。对照组术前仅应用基础用药:阿司匹林300 mg和氯吡格雷300 mg顿服。比较3组患者开通梗死相关动脉(IRA)后心肌梗死溶栓(TIMI)及心肌再灌注(MBG)2~3级血流率,术后90min心电图ST段回落百分比(sum-STR);术后左室射血分数(LVEF)、左室舒张末期内径(LVEDD)和左室收缩末期内径(LVESD)的变化;术后主要心脏不良事件(死亡、再梗死、靶血管重建和脑卒中)及出血、消化道不良症状的发生率。结果标准剂量组和低剂量组的TIMI及MBG 2~3级血流率较对照组高(P0.05),标准剂量组与低剂量组间差异无统计学意义;标准剂量组和低剂量组术后90 min sumSTR50%比例较对照组高,标准剂量组与低剂量组无统计学差异;3组患者住院期间不良事件发生率无统计学差异;低剂量组的出血发生率低于标准剂量组,差异有统计学意义(6.78%比21.05%,P0.05),低剂量组和对照组的出血发生率无差异。结论在老年STEMI接受急诊PCI治疗的患者中,低剂量替罗非班在预防缺血方面的疗效与标准剂量替罗非班相当,但在出血风险方面的安全性明显升高。     

Oral platelet glycoprotein IIb/IIIa receptor inhibitors--part II

Although the hypothesis of benefit from prolonged oral IIb/IIIa inhibition was appealing, the large Phase III trials have uniformly shown there was no improvement in outcome. In addition, there was an increased mortality seen in patients treated with the oral IIb/IIIa inhibitor. This latter finding is not adequately explained, but is likely a multifactorial problem of this strategy of platelet inhibition. The trials found that, even with no improvement in efficacy, there was increased bleeding, meaning that for chronic therapy with IIb/IIIa inhibition there does not appear to be a therapeutic window. Accordingly, chronic oral IIb/IIIa inhibition appears to have been well tested but has not worked. Fortunately, there are several other oral antiplatelet agents available that have shown beneficial results, including clopidogrel. In addition, other newer classes of antiplatelet agents are in earlier stages of development. Thus, agents targeted more "upstream" in platelet activation pathways may offer a more tolerable and efficacious approach to long-term antiplatelet therapy.