Antiplatelet therapy for elective coronary stenting: a moving target

The recognition of the major contribution of platelet-mediated mechanisms to the pathogenesis of thrombotic complications after coronary stenting has led to the development and evaluation of different antiplatelet regimens. The combination of aspirin and adenosine diphosphate antagonists such as ticlopidine and clopidogrel has solved the issue of acute stent thrombosis. The timing and dose of dual oral antiplatelet therapy have, however, changed over time with a shift from postintervention treatment to preintervention treatment with a high loading dose of clopidogrel. Pretreatment with aspirin and clopidogrel has been associated with a further 30% reduction in ischemic complications after coronary intervention. Recent data have even shown that in case of optimal pretreatment with such a dual oral antiplatelet therapy, glycoprotein IIb/IIIa antagonists are no longer mandatory for elective coronary stenting and should be reserved only for high-risk procedures or for acute coronary interventions.     

Focused clinical review: periprocedural management of antiplatelet therapy in patients with coronary stents

Coronary stent implantation, particularly drug eluting stents, is now the major method of coronary revascularisation. Following drug-eluting stent implantation dual antiplatelet therapy with aspirin and thienopyridine is recommended for at least 12 months. Premature discontinuation, often at the time of noncardiac surgery, has been associated with stent thrombosis which has a significant risk of death and myocardial infarction. Late (>30 days) and very late (>365 days) stent thrombosis appears to more common with DES and poses the questions of when is it safe to stop antiplatelet therapy post coronary stenting and how to manage patients who need non-cardiac surgery. This article reviews the evidence for stent thrombosis and the peri-operative management of patients with coronary stents and provides an algorithm for patient management based on multidisciplinary assessment of bleeding risk, perioperative cardiac event and stent thrombosis risk.     

Triple versus dual antiplatelet therapy after coronary stenting: impact on stent thrombosis.

OBJECTIVES: We evaluated safety and efficacy of triple antiplatelet therapy with aspirin, clopidogrel, or ticlopidine and cilostazol after coronary stenting. BACKGROUND: Triple antiplatelet therapy might have beneficial effect to prevent thrombotic complications in patients undergoing coronary stenting. METHODS: Patients undergoing successful coronary stenting were divided into dual antiplatelet therapy (aspirin plus clopidogrel or ticlopidine, group I, n = 1,597) and triple antiplatelet therapy (aspirin plus clopidogrel or ticlopidine plus cilostazol, group II, n = 1,415) groups. The primary end point included death, myocardial infarction, target lesion revascularization, or stent thrombosis within 30 days. The secondary end point was side effects of study drugs, including major bleeding, vascular complication, hepatic dysfunction, and hematological complications. RESULTS: Multi-vessel stenting and the use of long stents were more prevalent in group II than in group I. The primary end point was 0.8% in group I and 0.3% in group II (p = 0.085). Stent thrombosis within 30 days was significantly lower in group II (n = 1, 0.1%) than in group I (n = 9, 0.5%; p = 0.024). The independent predictors of stent thrombosis were primary stenting (odds ratio [OR] 7.9, 95% confidence interval [CI] 2.0 to 30.8, p = 0.003) and triple therapy (OR 0.12, 95% CI 0.015 to 0.98, p = 0.048). The overall adverse drug effects, including major bleeding, neutropenia, and thrombocytopenia, were no different between two groups (1.8% vs. 2.6%, p = 0.104). CONCLUSIONS: Compared with the dual antiplatelet regimen, triple antiplatelet therapy seemed to be more effective in preventing thrombotic complications after stenting without an increased risk of side effects. Triple antiplatelet therapy might be safely applied in patients or lesions with a high risk of stent thrombosis.     

Does pre-treatment with aspirin and loading dose clopidogrel obviate the need for glycoprotein IIb/IIIa antagonists during elective coronary stenting? A focus on peri-procedural myonecrosis.

AIMS: Although full platelet inhibition with aspirin and thienopyridines before coronary stenting has significantly reduced the risk of acute stent thrombosis, peri-procedural myonecrosis still occurs frequently and is associated with increased death rate. Whether further inhibition of platelet aggregation by a glycoprotein IIb/IIIa antagonist may provide an additional cardioprotection is unknown. METHODS AND RESULTS: A total of 200 patients pre-treated with aspirin and a loading dose of clopidogrel (450 mg) were randomized just before coronary intervention (percutaneous coronary intervention, PCI) to treatment with or without abciximab. Platelet aggregation was assessed in samples collected during the procedure and the degree of platelet aggregation inhibition was correlated with cardiac enzyme release post-PCI. Abciximab treatment achieved a more complete inhibition of aggregation than dual oral antiplatelet therapy alone (median value of 1 vs. 50%, normal 100%). Any pathological increase in creatinine kinase-MB (CK-MB) post-PCI was present in 21% of the abciximab group and in 22% of the no-abciximab group (P = 0.9). Also the occurrence of clinically relevant myonecrosis [myocardial infarction (MI) = CK-MB > 3x upper limit of normal] was not significantly influenced by treatment assignment: 9 vs. 10% (P = 0.9). In a multiple logistic regression model including clinical, angiographic, and procedural characteristics, post-PCI myonecrosis was not correlated with the degree of platelet aggregation inhibition but with procedural features (such as long inflation time) and with the presence of multi-vessel disease. There were no cases of acute or subacute stent thrombosis. At 6 months, major adverse cardiac events, including cardiac death, non-fatal MI, or target lesion revascularization occurred in 13% of abciximab patients and in 16% of the control patients (P = 0.6). CONCLUSIONS: In the studied patients scheduled for elective coronary stenting and pre-treated with aspirin and a loading dose of clopidogrel, further inhibition of platelet aggregation by abciximab does not afford additional cardioprotection. Our data suggest that distal athero-embolization rather than thrombo-embolization is involved in the phenomenon of myonecrosis post-elective stenting.     

Clopidogrel treatment surrounding percutaneous coronary intervention: When should it be started and stopped?

Clopidogrel pretreatment before percutaneous coronary intervention (PCI) has been shown to decrease major adverse cardiovascular events (MACE) at 1 month. This benefit has been demonstrated in patients spanning the entire spectrum of coronary artery disease. Subsequent dual antiplatelet therapy with aspirin and clopidogrel after stent placement is necessary for the prevention of stent thrombosis. The duration of clopidogrel therapy after stent placement is dependent upon the type of stent placed, and is recommended for a minimum of 4 weeks after bare-metal stent placement, 3 months after sirolimus-eluting stent placement, and 6 months after paclitaxel-eluting stent placement. A longer course of therapy with clopidogrel (12 months) has been recommended by the most recent American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions guidelines for PCI based upon incremental reduction in cardiovascular complications (primarily myocardial infarction). This article reviews the data presently available regarding pretreatment with clopidogrel before PCI, and the strength of evidence supporting long-term dual antiplatelet therapy.     

Clinical Considerations with the Use of Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention

Despite the proven benefits of using antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI), a number of key questions remain to be answered. In recent years, clopidogrel dosing strategies among such patients have evolved considerably, with newer approaches involving loading doses prior to PCI and increases in the time interval and loading dosage in an effort to overcome variable responsiveness/hyporesponsiveness to platelet inhibition. Further, the role of glycoprotein (GP) IIb/IIIa antagonists in elective stenting continues to be defined, with recent evidence suggesting that most appropriate use of these agents is in high‐risk patients with elevated troponin levels. There appears to be a relationship between the use of GP IIb/IIIa antagonists with clopidogrel loading and attenuation of early inflammatory and cardiac marker release. Strategies to minimize the chance of late stent thrombosis in patients who receive drug‐eluting stents (DES) are also under intense investigation. Among some patients receiving sirolimus and paclitaxel DES, current standard long‐term antiplatelet strategies may be insufficient. Patient nonadherence to treatment and premature discontinuation and underutilization of antiplatelet therapies by physicians remain important clinical problems with potentially dire consequences. Copyright © 2008 Wiley Periodicals, Inc.     

Successful Therapy With Ticagrelor in Three-Vessel Stent Thrombosis Related to Clopidogrel Resistance

A 65-year-old man developed 3-vessel stent thrombosis after percutaneous coronary intervention with aspirin and clopidogrel. Platelet tests revealed clopidogrel resistance, which resolved after changing clopidogrel to ticagrelor. Although routine platelet tests after stenting are not recommended, these tests may be considered to identify the cause of stent thrombosis and modify antiplatelet therapy.     

Design and Rationale of the RE‐DUAL PCI Trial: A Prospective,Randomized, Phase 3b Study Comparing the Safety and Efficacy of Dual Antithrombotic Therapy With Dabigatran Etexilate Versus Warfarin Triple Therapy in Patients With Nonvalvular Atrial Fibrillation Who Have Undergone Percutaneous Coronary Intervention With Stenting

Antithrombotic management of patients with atrial fibrillation (AF) undergoing coronary stenting is complicated by the need for anticoagulant therapy for stroke prevention and dual antiplatelet therapy for prevention of stent thrombosis and coronary events. Triple antithrombotic therapy, typically comprising warfarin, aspirin, and clopidogrel, is associated with a high risk of bleeding. A modest‐sized trial of oral anticoagulation with warfarin and clopidogrel without aspirin showed improvements in both bleeding and thrombotic events compared with triple therapy, but large trials are lacking. The RE‐DUAL PCI trial (NCT 02164864) is a phase 3b, a strategy of prospective, randomized, open‐label, blinded‐endpoint trial. The main objective is to evaluate dual antithrombotic therapy with dabigatran etexilate (110 or 150 mg twice daily) and a P2Y12 inhibitor (either clopidogrel or ticagrelor) compared with triple antithrombotic therapy with warfarin, a P2Y12 inhibitor (either clopidogrel or ticagrelor, and low‐dose aspirin (for 1 or 3 months, depending on stent type) in nonvalvular AF patients who have undergone percutaneous coronary intervention with stenting. The primary endpoint is time to first International Society of Thrombosis and Hemostasis major bleeding event or clinically relevant nonmajor bleeding event. Secondary endpoints are the composite of all cause death or thrombotic events (myocardial infarction, or stroke/systemic embolism) and unplanned revascularization; death or thrombotic events; individual outcome events; death, myocardial infarction, or stroke; and unplanned revascularization. A hierarchical procedure for multiple testing will be used. The plan is to randomize ～ 2500 patients at approximately 550 centers worldwide to try to identify new treatment strategies for this patient population.     

药物洗脱支架置入后血栓形成的原因分析

目的探讨药物洗脱支架置入后血栓形成的发生率以及血栓形成的原因。方法本研究为单中心药物洗脱支架的注册研究,自2001年12月至2005年12月共计3345例冠心病患者接受了药物洗脱支架的治疗,其中使用雷帕霉素洗脱支架（SES）2165例,使用紫杉醇洗脱支架（PES）1180例,完成10个月临床随访为2296例;所有患者均同时口服阿司匹林和氯吡格雷至少9个月。结果3345例患者中9例发生急性血栓形成（O．27％）,其中7例为SES、2例为PES所致（0．32％比0．17％,P=0．637）;7例发生亚急性血栓形成（0．21％）,其中5例为SES、2例为PES所致（0．23％比0．17％,P=0．526）;急性和亚急性血栓发生率为0．48％（16／3345）;13例有晚期血栓形成,5例为SES、8例为PES所致（0．34％比0．95％,P=0．114）;4例晚期血栓形成的主要原因为提前中断抗血小板药物,既往患有心肌梗死病史,心功能差,药物洗脱支架置入后晚期发生血栓致猝死6例。结论支架置入不满意,特别是分叉病变以及支架未能完全覆盖受损伤的病变段是急性和亚急性血栓形成的主要原因;中断抗血小板药物和左心功能不全是晚期血栓形成的主要原因。     

长期负荷量硫酸氢氯吡格雷显著降低血小板高反应性患者PCI术后心血管缺血事件发生率

目的 观察长期负荷量使用硫酸氢氯吡格雷对血小板高反应性患者PCI术后心血管缺血事件发生率的影响。方法 采用血栓弹力仪检测硫酸氢氯吡格雷的药物效果,筛选PCI术后对硫酸氢氯吡格雷药物不敏感患者（血小板高反应性患者）作为研究对象,随机分为对照组及试药组,每组患者各60例,对照组每天服用100 mg阿司匹林及75 mg硫酸氢氯吡格雷,试药组服用100 mg阿司匹林以及150 mg硫酸氢氯吡格雷,检测6个月后硫酸氢氯吡格雷的药物效果,同时观察两组6个月内心血管事件的发生率。结果 6个月内试药组心血管病病死率、支架内血栓再形成率、再发心肌梗死和再发不稳定心绞痛发生率分别为0%、10%、23%以及6%,对照组为3%、20%、36%以及17%,试药组显著低于对照组,试药组硫酸氢氯吡格雷所致血小板抑制率明显高于对照组,两组患者出血风险无显著性差异。结论对于血小板高反应性患者,长期加倍剂量服用硫酸氢氯吡格雷可降低心血管缺血事件发生率。     

Poor responsiveness to antiplatelet drugs in acute coronary syndromes: clinical relevance and management

Cardiovascular diseases are the most common cause of mortality and morbidity in Western countries, accounting for more than 40% of total mortality. An optimal pharmacological management in these patients is of major importance and antiplatelet agents remain the cornerstone of acute coronary syndrome (ACS) therapy at hospital admission and during percutaneous coronary interventions (PCI). The recently described poor biological responses to aspirin and clopidogrel have been source of major concern, especially in era of drug eluting stent implantation. Indeed, insufficient platelet inhibition at the time of PCI has been consistently associated with an increased risk of complications and recurrence of ischemic events. Despite the lack of uniformly accepted definitions of aspirin and clopidogrel poor response, we sought to describe the current evidence and gaps in knowledge. While trials on the potential benefit of an increased antiplatelet maintenance dose after PCI have shown only marginal benefits, the strengthening of the initial antiplatelet regimens by additional loading doses of clopidogrel, by the administration of glycoprotein IIb/IIIa receptor inhibitors or phosphodiesterase inhibitors might further improve outcomes during ACS and PCI in patients with poor responsiveness to conventional dual antiplatelet therapy. Overall, tailoring the antiplatelet treatment on the basis of the individual biological response improves the short-term outcome after PCI. New and more potent antiplatelet drugs may overcome the clinical consequences of the poor response to antiplatelet agents.     

Optimizing antiplatelet therapy in acute coronary syndrome and percutaneous coronary intervention

Dual antiplatelet therapy with aspirin and clopidogrel is the standard of care for patients with acute coronary syndrome (ACS) and those undergoing percutaneous coronary intervention (PCI). It is well established that inhibition of platelet aggregation reduces the risk of recurrent thrombotic events and stent thrombosis. However, some patients show a reduced antiplatelet response to standard clopidogrel loading (300 mg) and maintenance (75 mg day^?1) doses, which has been associated with poorer patient outcomes. Pharmacodynamic and pharmacokinetic studies show that higher‐than‐standard clopidogrel dosing strategies facilitate more rapid platelet inhibition of a greater intensity as a result of greater plasma concentrations of the clopidogrel active metabolite. Recently completed studies suggest that in patients with ACS undergoing PCI, higher‐than‐standard clopidogrel dosing regimens provide greater inhibition of platelet function and improved clinical outcomes with a small but significant increase in major bleeding. Newer, more potent antiplatelet agents such as prasugrel and ticagrelor are other alternative strategies that result in more rapid, greater inhibition of platelet function and better outcomes than standard‐dose clopidogrel. Whether platelet reactivity‐guided therapy or genotyping for cytochrome P450 polymorphisms is useful in managing patients needs to be further defined. Most importantly, early and effective antiplatelet therapy results in the best short‐ and long‐term outcomes for patients with ACS or those undergoing PCI. © 2011 Wiley‐Liss, Inc.     

Recurrent episodes of very late stent thrombosis in a patient with aspirin hypersensitivity, stent fracture and malapposition

Late stent thrombosis represents a life-threatening event, usually triggered by inadequate antiplatelet therapy and promoted by multiple risk factors, such as stenting of a chronic total occlusion, overlapping stenting, an abnormal vascular response to the eluted drug, stent malapposition and stent fracture. A 57-year-old man with aspirin hypersensitivity underwent successful percutaneous revascularization of a chronic total occlusion of the left anterior descending artery (LAD). He received two sirolimus-eluting stents overlapping for 2 mm and was discharged on clopidogrel and picotamide. Two years later, 15 days after clopidogrel discontinuation, he experienced an anterior ST-segment elevation myocardial infarction and underwent rescue percutaneous LAD thrombectomy after unsuccessful fibrinolysis. Coronary angiography showed fracture of the distal stent, with a 5 mm gap between the two portions, as well as severe late stent malapposition, confirmed by optical coherence tomography. Despite treatment with clopidogrel and picotamide, in the following days the patient experienced two new episodes of stent thrombosis, treated with thrombectomy and deployment of bioengineered stents. The patient underwent successful oral aspirin desensitization, with a complete in vitro inhibition of platelet function, and was discharged on aspirin, clopidogrel and warfarin, without experiencing other events at 6-month follow-up.     

Influence of low-dose aspirin (81 mg) on the incidence of definite stent thrombosis in patients receiving bare-metal and drug-eluting stents

Background:

Dual antiplatelet therapy with aspirin plus clopidogrel is the mainstay of therapy in patients undergoing percutaneous coronary intervention (PCI). However, the optimal dose of aspirin following PCI has not been established.

Hypothesis:

There is no difference for definite stent thrombosis in patients taking low dose versus standard aspirin.

Methods:

Low‐dose (81 mg) aspirin was used as part of a standard dual antiplatelet therapy in patients receiving bare‐metal stents (BMS) or drug‐eluting stents (DES) at a large tertiary medical center. We retrospectively analyzed 5368 consecutive cases treated with stent placement and dual antiplatelet therapy. The incidence of definite stent thrombosis (DST) at our institution was compared to DST as reported in a large, published cohort of 24 trials and 12973 patients. We stratified DST events into early (<30 days) and late (>30 days) timing and also stratified by stent type. The effect of aspirin dosing was evaluated using χ², Cochran‐Mantel‐Haenszel, and homogeneity testing.

Results:

A total of 5187 patients underwent 7604 stent implantations during the study period. The cumulative incidence of DST was 0.60% (95% confidence interval [CI], 0.42%–0.84%) at 30 days and 0.76% (95% CI, 0.56%–1.03%) at 1 year. The overall incidence of DST during the study period was not different based on type of stent (0.53% for DES and 0.75% for BMS, P = 0.36). Compared to the historic, standard‐dose aspirin (162–325 mg) cohort, DST in our low‐dose aspirin (81 mg) cohort was not significantly different at either 30 days (0.72% vs 0.60%, P = 0.39) or at 1 year (1.08% vs 0.76%, P = 0.07). There was no appreciable interaction of aspirin dose on the incidence of DST, controlling for stent type, or timing of the event.

Conclusions:

Low‐dose aspirin therapy in combination with clopidogrel following implantation of either BMS or DES in our cohort does not appear to increase the risk of DST compared to a higher‐dose aspirin regimen. © 2011 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.     

Frequency and correlates of coronary stent thrombosis in the modern era: analysis of a single center registry

OBJECTIVES: The study examined the frequency, correlates, and outcome of patients with stent thrombosis within 30 days of stent placement. BACKGROUND: Patients in trials evaluating stents or dual antiplatelet therapy to prevent coronary stent thrombosis have generally had narrow inclusion criteria; the extent to which stent thrombosis rates in such trials represent current practice, particularly with the availability of newer stents, is unclear. METHODS: We performed a retrospective analysis of the Mayo Clinic Percutaneous Coronary Intervention database and identified all patients who received at least one coronary stent and dual antiplatelet therapy (aspirin and ticlopidine or clopidogrel for two to four weeks). RESULTS: Four thousand five hundred nine patients underwent successful coronary stent implantation and were treated with dual antiplatelet therapy between July 1, 1994, and April 30, 2000. Stent thrombosis occurred in 23 patients (0.51%; 95% confidence interval 0.32%, 0.76%) within 30 days of stent placement. Multivariate analysis using bootstrap model selection to avoid over-fitting the model indicated that only the number of stents placed was an independent correlate of stent thrombosis (odds ratio 1.80, p < 0.001). The frequency of death and frequency of nonfatal myocardial infarction (MI) among the 23 patients with stent thrombosis were 48% and 39%, respectively. CONCLUSIONS: Stent thrombosis is even more rare in the current era than in earlier trials. Number of stents placed was an independent correlate of stent thrombosis. Most patients who suffer stent thrombosis either die or suffer MI.     

Combination therapy with clopidogrel and aspirin after coronary stenting.

Combination antiplatelet therapy using aspirin and ticlopidine has been the standard of care for prevention of subacute thrombosis following coronary stent implantation. However, the use of ticlopidine is associated with a significant risk of adverse hematologic side effects. Clopidogrel is an inhibitor of ADP-induced platelet aggregation that has a better safety profile than ticlopidine. We examined the 30-day clinical outcome following coronary stent implantation in 253 consecutive patients treated with clopidogrel and aspirin. Follow-up was achieved in 99% of patients and four adverse events were documented. Two patients had angiographically confirmed subacute stent thrombosis (0.8%), and both of these patients underwent successful repeat angioplasty at the stent site. There were two patient deaths during follow-up (0. 8%). One was sudden within 1 week of stent placement and the other occurred in a patient with multisystem organ failure after an extensive myocardial infarction that antedated the stent procedure, with no clinical evidence for stent thrombosis. The combined frequency of subacute stent thrombosis and death was 1.6%. This is comparable to prior studies using the combination of ticlopidine and aspirin following stenting. Therefore, clopidogrel in combination with aspirin appears to be a safe and effective therapy in the prevention of subacute thrombosis following coronary stent implantation.     

The role of clopidogrel in the management of ischemic heart disease

PURPOSE OF REVIEW: Platelet inhibition remains a key component in the prevention and treatment of ischemic heart disease. This review documents recent advances in the use of clopidogrel for the management of myocardial ischemia. RECENT FINDINGS: For the prevention of ischemic heart disease, the addition of clopidogrel is not superior to aspirin alone at reducing short or long-term major adverse cardiac events. In patients with ST-segment elevation myocardial infarction who receive thrombolytics, clopidogrel therapy confers broad benefits including survival when initiated at the time of presentation. Long-term administration of clopidogrel is necessary to prevent thrombotic complications following coronary stent placement. Overall, there are no major safety concerns across the spectrum of cardiac indications for clopidogrel. SUMMARY: Clopidogrel has become a cornerstone of therapy in the treatment of acute ischemic coronary syndromes and as prevention of thrombosis after coronary stenting. It has demonstrated safety and efficacy in most aspects of ischemic heart disease. Questions remain about optimal duration of therapy following deployment of drug-eluting stents.     

High on treatment platelet reactivity

The addition of clopidogrel to aspirin for patients undergoing percutaneous coronary intervention (PCI) had significantly reduced cardiovascular events. However, despite dual antiplatelet therapy ischaemic events still occur, especially stent thrombosis, which is associated with a high mortality rate. Inter-individual response to clopidogrel is highly variable. It was shown that 4-46% could be considered as high on treatment platelet reactivity (HTPR). Recent studies had demonstrated a relationship between HTPR and ischaemic events in the setting of PCI. Actually the assessment of platelet reactivity in routine practice and its interpretation to make a decision is a debatable issue.     

Overcoming Aspirin Resistance with Loading Clopidogrel Earlier in Elective Percutaneous Coronary Intervention

We aimed to analyze the clinical effect of clopidogrel loading time on adverse cardiovascular events among patients with aspirin resistance. Recurrent adverse events may still occur despite dual antiplatelet therapy after coronary stenting. Aspirin resistance is one of the possible reasons of this trouble. Optimal antiplatelet strategy for coronary stenting is unknown among patients with aspirin resistance. A total of 980 patients scheduled for elective coronary stenting were enrolled and allocated into two groups according to the loading time of clopidogrel more or less than 6 hours before coronary intervention (early- or late-loaded groups, respectively). Aspirin resistance was determined according to the urinary levels of 11-dehydrothromboxane B2. Overall 240 patients who were allocated to early- and late-loaded groups were identified as aspirin resistant according to the urinary levels of 11-dehydrothromboxane B2. After a follow-up period of 12 months major adverse cardiac events were observed among 16 patients (13.9%) in the early-loaded group and 30 patients (25.8%) in the late-loaded group (p = 0.02). Early loading of clopidogrel was an independent predictor of lower rate of cardiac events (hazard ratio = 0.46 [0.32–0.76, 95% confidence interval], p = 0.001). The rates of bleeding events and periprocedural myocardial infarction were similar in early- and late-loaded groups. The current study demonstrated that loading of clopidogrel earlier than 6 hours before elective coronary stenting among aspirin-resistant patients was associated with increased benefits for ischemic events with similar bleeding rates.     

替格瑞洛用于经皮冠状动脉介入治疗术后患者抗血小板治疗短期内的有效性和安全性研究

目的：观察替格瑞洛用于经皮冠状动脉介入治疗（PCI）患者抗血小板治疗的有效性和安全性。方法选择50例冠心病PCI术后应用氯吡格雷抗血小板,因血小板聚集率不达标且CYP2C19基因异常而改用替格瑞洛的患者。所有入选患者应用阿司匹林首次负荷剂量300 mg,维持剂量100 mg,每日一次;替格瑞洛维持剂量90 mg,每日二次,持续1年。研究主要终点为随访1个月的主要不良心血管事件（包括死亡、支架内血栓形成、支架内再狭窄、非致死性心肌梗死、靶血管血运重建）和脑卒中的发生率;次要终点为一般不良事件（包括轻微出血、过敏、呼吸困难）的发生率及血小板计数的变化情况。结果患者应用替格瑞洛后随访1个月未出现主要不良心血管事件和脑卒中;一般不良事件的发生率较低,2例（4%）出现呼吸困难,2例（4%）发生轻微出血,其中1例鼻出血,1例皮下淤血。应用替格瑞洛后血小板聚集率明显低于氯吡格雷,血小板计数未明显下降。结论替格瑞洛用于存在氯吡格雷抵抗的PCI患者抗血小板治疗,短期内安全有效。