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Onset and extent of platelet inhibition by clopidogrel loading in patients undergoing elective coronary stenting: The Plavix Reduction Of New Thrombus Occurrence (PRONTO) trial

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AMERICAN HEART JOURNAL 2003年第2期145卷 239-247页

作者： Gurbel, PA Cummings, CC Bell, CR Alford, AB Meister, AF Serebruany, VL Sinai Hosp Sinai Ctr Thrombosis Res Baltimore MD 21215 USA

Background Despite the common practice of clopidogrel loading for coronary stenting, the time dependence and degree of platelet inhibition after this therapy are not well defined. We sought to establish an optimal clopidogrel dosing regimen for sustained platelet inhibition in stented patients. Methods and Results Platelets were assessed by conventional aggregation with 5 mumol/L adenosine diphosphate (ADP), 1 mug/mL collagen (COLL), and 750 mumol/L arachidonic acid;whole blood aggregation by 1 mug/mL collagen (WBA);shear-induced closure time (CT);contractile force (CF);and expression of 9 surface receptors by flow cytometry in 100 patients undergoing elective stent placement without glycoprotein (GP) IIb/IIIa receptor antagonists. Blood was obtained at baseline and serially over 5 days poststenting after different clopidogrel loading regimens: 300 mg 24 hours before (Group A), 12 hours before (Group B), 3, to 6 hours before (Group C), and 75 mg at the time of intervention (Group D). Before stenting, ADP, COLL, CT, and WBA were reduced by clopidogrel loading (P < .05). CF was not affected by clopidogrel. Before stenting, GP IIb/IIIa expression increased in groups A through C (P < .05), whereas PE-CAM-1 and CD107a were reduced (P < .05). At 2 hours and 2 days poststenting, platelets, in general, exhibited an increase in activity that was most inhibited by clopidogrel loading. Clopidogrel inhibited GP Ib, platelet/endothelial cell adhesion molecule-1, CD 107a, CD 151, and GP IIb/IIIa expression at day 5 poststenting. Conclusion A 300 mg clopidogrel load given 3 to 24 hours before stenting inhibits platelets at the time of the procedure and reduces poststent activity more than a 75 mg dose given at the time of the procedure. The inhibition of adhesive molecule expression may also contribute an antithrombotic effect. Poststent activation of platelets may warrant higher periprocedural dosing.

关键词：血管成形术经腔经皮冠状动脉抗原 CD/血液胶原/药理学冠心病冠状动脉血栓形成/病因学冠状动脉血栓形成/预防和控制用药计划表血小板聚集/药物作用血小板聚集抑制剂/投药和剂量血小板膜糖蛋白类/代谢单盲法噻氯匹定/投药和剂量噻氯匹定/类似物和衍生物老年人女(雌)性人类男(雄)性

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A randomized trial assessing the effect of coumarins started before coronary angioplasty on restenosis: Results of the 6-month angiographic substudy of the Balloon Angioplasty and Anticoagulation Study (BAAS)

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AMERICAN HEART JOURNAL 2003年第1期145卷 58-65页

作者： ten Berg, JM Kelder, JC Suttorp, MJ Verheugt, FWA Plokker, HWT St Antonius Hosp Dept Intervent Cardiol NL-3435 CM Nieuwegein Netherlands Univ Nijmegen Med Ctr Dept Cardiol Nijmegen Netherlands

Background Thrombus formation during coronary angioplasty may play a role in the restenosis process. Methods The effect of pretreatment with coumarins on 6-month angiographic outcome was studied. In addition, the effect of "optimal" anticoagulation, defined as an international normalized ratio >70% of the follow-up time in the target range, was studied. A total of 261 patients were assigned to aspirin alone (ASA group) and 270 patients to aspirin plus coumarins started I week before the procedure (coumarin group). Results The mean international normalized ratio was 2.7 +/- 1.2 at the start of the procedure and 3.1 +/- 0.5 during follow up. Quantitative coronary analysis was performed on 301 lesions in the ASA group and of 297 lesions in the coumarin group. At 6 months, the minimal luminal diameter was similar in the ASA and coumarin groups. Optimal anticoagulation, however, was an independent predictor of a larger minimal luminal diameter at follow up (P = .01). Conclusion Overall, coumarins do not improve angiographic outcome 6 months after coronary angioplasty.

关键词：阿司匹林/投药和剂量冠状血管造影术冠状动脉血栓形成/病因学冠状动脉血栓形成/预防和控制冠状动脉血栓形成/放射摄影术香豆素类/投药和剂量无病生存随访研究多元分析术前用药法复发/预防和控制治疗结果女(雌)性人类男(雄)性中年人

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Safety and efficacy of only 2 weeks of ticlopidine therapy in patients at increased risk of coronary stent thrombosis: Results from the Antiplatelet Therapy alone versus Lovenox plus Antiplatelet therapy in patients at increased risk of Stent Thrombosis (ATLAST) trial

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AMERICAN HEART JOURNAL 2002年第5期143卷 841-846页

作者： Berger, PB Mahaffey, KW Meier, SJ Buller, CE Batchelor, W Fry, ETA Zidar, JP Mayo Clin Div Cardiovasc Dis Rochester MN 55905 USA Duke Univ Clin Res Inst Durham NC USA Rhone Poulenc Rorer Collegeville PA USA Vancouver Hosp Vancouver BC Canada Terrence Donnelly Heart Ctr Toronto ON Canada St Vincents Hosp Indianapolis IN USA

Background Controversy exists regarding the frequency of late stent thrombosis among patients treated with intracoronary stents and the most appropriate duration of treatment with a thienopyridine that is required to prevent this complication. Methods We analyzed the frequency of stent thrombosis and other ischemic events in the Antiplatelet Therapy alone versus Lovenox plus Antiplatelet therapy in patients at increased risk of Stent Thrombosis (ATLAST) trial. In the ATLAST trial, 1102 patients at increased risk of stent thrombosis (ST-elevation myocardial infarction within 48 hours, diffuse distal disease, a large amount of thrombus, acute closure, residual dissection, etc) were randomly assigned to receive either enoxaparin (40 or 60 mg given every 12 hours for 14 days) or placebo;all patients received aspirin (325 mg daily) and ticlopidine (250 mg twice daily) for only 14 days. Results The primary end point, the 30-day combined incidence of death, nonfatal myocardial infarction, and urgent revascularization, was reached in 2.3% of patients (1.8% of patients taking enoxaparin vs 2.7% of patients taking placebo;P = .295). However, during the 15th through 30th days, the frequency of ischemic events was only 0.73%, and only 0.27% (3/1102) of patients had possible stent thrombosis (95% CI 0.06, 0.77). Conclusion The frequency of stent thrombosis and other adverse ischemic events in the 15th through 30th days after stent placement in even high-risk stent patients treated with ticlopidine for only 2 weeks is low whether or not enoxaparin is administered.

关键词：冠状动脉血栓形成/病因学冠状动脉血栓形成/预防和控制冠状动脉血栓形成/治疗依诺肝素/投药和剂量纤维蛋白溶解药/投药和剂量血小板聚集抑制剂/投药和剂量噻氯匹定/投药和剂量时间因素女(雌)性人类男(雄)性中年人

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Enoxaparin in acute coronary syndromes: Evidence for superiority over placebo or untreated control

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AMERICAN HEART JOURNAL 2002年第5期143卷 748-752页

作者： Massel, D Cruickshank, MK Univ Western Ontario London Hlth Sci Ctr Dept Med London ON N6A 4G5 Canada

Background Heparins, both standard unfractionated heparin (SUFH) and low-molecular weight heparin, play a prominent role in the treatment of acute coronary syndromes. Enoxaparin has been shown in 2 trials to be superior to heparin but has not been compared with placebo or untreated control. Methods A putative enoxaparin versus placebo/control odds ratio (OR) was computed with a recently described statistical technique with the logarithm of the ORs of the pooled results of both the enoxaparin-SUFH trials and SUFH-placebo or controlled trials. Results The combined heparin versus control results show a 33% reduction in the risk of death or acute myocardial infarction (AMI), with an OR of 0.67 (95% confidence interval [CI], 0.45 to 0.99). At up to 12 weeks (data from only 4 trials), the combined results show a 21% reduction (OR, 0.79;95% CI, 0.54 to 1. 15;P = .23). The 2 enoxaparin trials show a nonsignificant 20% reduction in the risk of death or AMI during treatment (OR, 0.80;95% CI, 0.68 to 1.16;P = .24) and a significant reduction at 43 days (OR, 0.82;95% CI, 0.69 to 0.97;P = .022). With these pooled data, the putative OR for enoxaparin versus placebo/untreated control during treatment is 0.53 (95% CI, 0.31 to 0.92;P = .023). The data are consistent with a 47% reduction in the risk of death or AMI. The difference persists on longer term follow-up period (OR, 0.65;95% CI, 0.43 to 0.98;P = .04). The risk of bleeding is nonsignificantly increased (OR, 2.32;95% CI, 0.8 to 7.85;P = .51). Conclusion On the basis of this methodology, enoxaparin would appear to be more effective than placebo when added to aspirin in acute coronary syndromes. Moreover, the effect of enoxaparin is similar to the results of a metaanalysis of trials of other low-molecular weight heparins versus placebo/control.

关键词：抗凝药/治疗应用阿司匹林/治疗应用置信区间冠状动脉血栓形成/死亡率冠状动脉血栓形成/预防和控制药物疗法联合依诺肝素/治疗应用纤维蛋白溶解药/治疗应用肝素低分子量/治疗应用心肌梗死/死亡率心肌梗死/预防和控制比值比综合征人类

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香豆素加阿司匹林预防冠脉复塞

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国际医药卫生导报 2002年第10期 100-101页

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Abciximab, ticlopidine, and concomitant abciximab-ticlopidine therapy: Ex vivo platelet aggregation inhibition profiles in patients undergoing percutaneous coronary interventions

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AMERICAN HEART JOURNAL 2000年第3期140卷 492-501页

作者： Kleiman, NS Grazeiadei, N Maresh, K Taylor, RJ Frederick, B Lance, ET Effron, MB Jordan, RE Mascelli, MA Baylor Coll Med Houston TX 77030 USA Methodist Hosp Houston TX 77030 USA Eli Lilly & Co Indianapolis IN 46285 USA Centocor Inc Malvern PA 19355 USA

Background We examined the ex vivo platelet aggregation profiles of patients who underwent percutaneous coronary intervention and received either abciximab, ticlopidine, or both agents. Study Design and Methods The trial was a prospective, nonrandomized, single-center, open-label study of 42 patients undergoing percutaneous coronary intervention who received the Following regimens: group 1, abciximab (0.25 mg/kg bolus and 12-hour, 0.125 mu g/kg per minute infusion);group 2, ticlopidine (250 mg twice daily For 14 consecutive days, initiated 12 to 18 hours before intervention);group 3, abciximab plus ticlopidine initiated 12 to 18 hours before procedure;and group 4, abciximab plus ticlopidine initiated 72 to 96 hours before procedure. Platelet aggregation measurements to adenosine diphosphate (ADP) and a thrombin receptor activating peptide (TRAP, 8 mu mol/l) were obtained before ticlopidine treatment, after initiation of ticlopidine, and immediately before abciximab treatment and intervention, then at several time periods after onset of abciximab treatment. Platelet surface abciximab levels were monitored by flow cytometry. Results Neither ticlopidine regimen resulted in appreciable platelet inhibition before intervention and before administration of abciximab. In the ticlopidine-only arm, suppression of platelet aggregation to the weakest stimuli (5 mu mol/l ADP;23% +/- 7.5%) was detected within 24 hours after intervention, with maximal inhibition to both 5 and 20 mu mol/L ADP observed 7 days after intervention (48% +/- 7.9% and 18% +/- 8.7%, respectively). In contrast, ticlopidine marginally suppressed TRAP-mediated platelet activation at times when maximal effects on ADP-mediated platelet aggregation were evident. Neither ticlopidine regimen appreciably enhanced platelet inhibition during or shortly after cessation of abciximab treatment. For all 3 abciximab treatment arms, profound inhibition of ADP-induced (>80%) and TRAP-induced (>65%) platelet aggregation was

关键词：抗体单克隆/投药和剂量冠状动脉血栓形成/病理生理学冠状动脉血栓形成/预防和控制药物疗法联合免疫球蛋白Fab片段/投药和剂量血小板聚集抑制剂/投药和剂量血小板功能试验手术后并发症/预防和控制前瞻性研究噻氯匹定/投药和剂量老年人女(雌)性人类男(雄)性中年人

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Transcatheter closure of fenestrations and excluded hepatic veins after Fontan: Versatility of the Amplatzer device

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AMERICAN HEART JOURNAL 2000年第3期140卷 534-540页

作者： Moore, JW Murdison, KA Baffa, GM Kashow, K Murphy, JD DuPont Hosp Children Nemours Cardiac Ctr Wilmington DE USA

Background The aim of this study was to evaluate the Amplatzer septal occluder (ASO) for transcatheter closure of fenestrations and excluded hepatic veins in patients after modified Fontan operations. Residual right-to-left shunts have improved surgical results of the Fontan operation. Shunt closure may eventually be desirable to eliminate hypoxemia and reduce risk of embolic complications. Methods and Results Ten patients with hypoxemia caused by residual shunts after Fontan procedures were evaluated for closure. After favorable results of test occlusion, all shunts were closed with the use of the ASO, Eight ASOs were used to close fenestrations in 7 patients with 6F transvenous sheaths, Three ASOs were used to close excluded hepatic veins in 3 patients with 6F venous sheaths and transbaffle punctures. Fluoroscopy and transesophageal echocardiography were used to guide device placement. Device placement in all patients was successful. All shunts were closed by angiography after device placement. While breathing room air, systemic oxygen saturation rose from 87.9% +/- 3.0% to 96.3% +/- 0.9% (P < .001) in the patients. There were no complications of the implant procedures and none noted in outpatient follow-up. Conclusions This experience suggests that the ASO is safe and effective for closing surgical shunts after Fontan procedures. The ASO design allows closure of excluded hepatic veins and has advantages over other devices in closure of fenestrations.

关键词：冠状动脉血栓形成/预防和控制 Fontan手术/仪器和设备心脏导管插入术/仪器和设备心脏导管插入术/方法心脏缺损先天性/外科学肝静脉/外科学手术后并发症/预防和控制假体植入支架青少年儿童儿童学龄前女(雌)性人类婴儿男(雄)性

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Studies published on clopidogrel-aspirin for coronary stent placement

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AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY 2000年第2期57卷 101-102页

作者： [Anonymous]

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Antithrombin activity during the period of percutaneous coronary revascularization - Relation to heparin use, thrombotic complications and restenosis

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 1999年第5期33卷 1248-1256页

作者： Matthai, WH Kurnik, PB Groh, WC Untereker, WJ Siegel, JE Univ Penn Sch Med Dept Med Philadelphia PA 19104 USA Univ Med & Dent New Jersey Robert Wood Johnson Med Sch Dept Med Camden NJ 08103 USA Univ Med & Dent New Jersey Robert Wood Johnson Med Sch Dept Med New Brunswick NJ 08903 USA

OBJECTIVES This study evaluated changes in antithrombin (AT) activity around the time of percutaneous transluminal coronary revascularization (PTCR) with unfractionated heparin anticoagulation and the effects these changes had on major thrombotic complications of PTCR. BACKGROUND Heparin is used during PTCR to prevent thrombosis. However, heparin, a cofactor for AT, causes AT activity to fall. AT activity <70% is associated with thrombosis. There is a prothrombotic state after heparin discontinuation that has not been well explained. METHODS Antithrombin activity was sampled at the start and end of PTCR and the next two mornings in 250 consecutive patients. We recorded occurrence of major thrombotic events, defined as 1) major thrombotic complications of PTCR;2) major in-lab thrombus formation;or 3) subacute occlusion. Discriminant analysis was employed to evaluate the relationship of AT activity to these events. Change in AT activity;and its relationship to heparin was evaluated. Evidence of restenosis at six months was obtained. RESULTS There were 14 major thrombotic events. Antithrombin activity <70%, was strongly (p = 0.006) associated with these events. The AT activity fell significantly through the morning after PTC-R when 21% of patients had AT activity < 70%;AT activity did not normalize until >20 h after heparin discontinuation. Pre-PTCR use of heparin led to lower AT activity in proportion to duration of heparin use. There was no relationship between;AT activity and restenosis. CONCLUSIONS Low AT activity may contribute to major thrombotic complications of PTCR. The way heparin is used before and after PTCR is important to development of low AT activity. (C) 1999 by the American College of Cardiology.

关键词：血管成形术气囊冠状动脉/副作用抗凝药/治疗应用抗凝血酶类/药物作用抗凝血酶类/代谢冠状血管造影术冠心病/血液冠心病/诊断显像冠心病/治疗冠状动脉血栓形成/血液冠状动脉血栓形成/病因学冠状动脉血栓形成/预防和控制随访研究肝素/治疗应用回顾性研究治疗结果女(雌)性人类男(雄)性

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Vale, warfarin: A stentorian farewell

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AMERICAN HEART JOURNAL 1999年第4期138卷 602-605页

作者： Tcheng, JE Kong, DF Duke Univ Med Ctr Dept Med Div CardiolDuke Clin Res Inst Durham NC 27710 USA

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