老年心房颤动高危患者抗凝治疗的药物选择及安全性

目的探讨老年心房颤动患者抗凝治疗的药物剂量选择及安全性。方法选择确诊的老年心房颤动患者210例,按照年龄将60～79岁130例作为老年段及≥80岁80例作为高龄段。2个年龄段患者按服药治疗不同分为老年华法林组30例、高龄华法林组30例,老年联合用药组50例(氯吡格雷75 mg+阿司匹林100 mg),老年阿司匹林组50例和高龄阿司匹林组50例(阿司匹林100 mg)。观察服用华法林剂量及国际标准化比值(INR);各组患者栓塞及出血发生率。结果高龄华法林组剂量(2.88±0.46)mg,INR 2.29±0.55,老年华法林组剂量(2.93±0.75)mg,INR 2.30±0.52,差异无统计学意义(P>0.05)。老年华法林组和高龄华法林组及老年联合用药组栓塞发生率明显低于老年阿司匹林组和高龄阿司匹林组(P<0.05)。与老年华法林组和高龄华法林组及老年阿司匹林组和高龄阿司匹林组比较,老年联合用药组出血发生率明显高(P<0.05)。结论老年心房颤动患者服用华法林或氯吡格雷+阿司匹林能更有效预防脑卒中事件的发生,老年、尤其是高龄高危患者服用华法林治疗,INR控制在1.5～2.5是安全、有效。对于不适合应用华法林的患者,可应用氯吡格雷+阿司匹林预防血栓形成。     

老年心房颤动患者抗栓治疗现状与安全性和疗效的对比研究

目的观察老年心房颤动(房颤)患者抗栓治疗现状与安全性和疗效的对比研究。方法选择老年房颤患者343例,根据抗栓治疗不同分为无抗栓组56例,阿司匹林组120例,氯吡格雷组24例,联合组20例(阿司匹林+氯吡格雷),华法林组106例,新型口服抗凝药(NOAC)组17例。分析各组血栓栓塞和出血事件发生情况。结果无抗栓组、阿司匹林组、氯吡格雷组、联合组、华法林组和NOAC组栓塞发生率比较,差异有统计学意义(48.2%vs37.5%vs 25.0%vs 25.0%vs 5.7%vs 5.9%,χ~2=76.02,P=0.000)。总出血发生率华法林组为13.2%,阿司匹林组为11.7%,联合组为10.0%,无抗栓组为5.4%,NOAC组为5.9%,氯吡格雷组为0,各组出血发生率比较,差异有统计学意义(χ~2=17.14,P<0.01)。结论老年房颤患者必须行抗栓治疗以减少脑卒中等栓塞事件发生风险,在抗栓治疗中首选华法林或NOAC治疗,NOAC在栓塞预防及出血风险方面并不优于华法林,尤其在中重度肾功能不全应注意大出血风险。     

206例老年心房颤动患者抗栓治疗及血管事件发生情况5年随访

目的分析老年心房颤动(房颤)患者近5年抗栓治疗现状及血管事件发生情况。方法回顾性分析2005年1月～2006年6月入住我院的年龄≥75岁房颤患者206例,记录主要合并疾病、抗栓治疗方法及5年内栓塞、严重出血及死亡事件发生情况。结果 206例房颤患者中共发生栓塞事件47次,年发生率为4.56%。严重出血事件3次,年发生率为0.29%。行阿司匹林抗血小板治疗70例,氯吡格雷治疗66例,氯吡格雷联合阿司匹林抗血小板治疗11例,未行抗栓治疗56例。行华法林抗凝治疗3例,随访期间更换为抗凝治疗11例。抗凝时间平均2年1个月。结论老年房颤患者栓塞事件年发生率高,预防栓塞具有重要的临床意义。华法林抗凝治疗率低,抗凝治疗时间短。     

三联抗栓治疗在冠心病患者中的合理应用

冠状动脉内支架置入术后患者常规需接受阿司匹林＋氯吡格雷的双联抗血小板治疗,而当患者同时存在抗凝治疗指征时,则需要阿司匹林＋氯吡格雷＋华法林的三联抗栓治疗,但随之而来的是显著出血风险。该文主要介绍三联抗栓治疗在冠心病患者中的合理应用。     

心房颤动患者卒中的药物预防策略——Missouri-Columbia大学心血管病中心

卒中是心房颤动的严重并发症。以往的预防措施包括口服阿司匹林和抗凝药。对不适合口服抗凝药的患者可以采用阿司匹林和氯吡格雷的联合治疗。但这种联合治疗在降低卒中风险的同时,却增加了出血的风险。对于心房颤动合并有不稳定型冠脉综合征者,或接受冠状动脉支架治疗,但又不适合接受三联治疗（阿司匹林、氯吡格雷、华法林）的患者,该中心采用阿司匹林和氯吡格雷。对于冠状动脉支架手术,要求介入专家优先考虑采用裸金属支架,以缩短患者依赖联合治疗的时间。     

长期口服华法林钠患者冠状动脉支架术后抗栓治疗方案的分析

目的:讨论长期口服抗凝剂患者冠状动脉支架术后的抗栓治疗方案。方法:选择长期口服华法林钠,并在北京安贞医院接受冠状动脉造影(CA)和支架术(PCI)的患者,对临床资料进行回顾性分析,根据患者出院用药方案进行分组,比较组间基线特征,以及支架术后再梗死、死亡、脑梗死及出血等事件之间的差别。结果:符合要求的90例患者分为华法林钠+氯吡格雷+阿司匹林三联治疗组(A组)、华法林钠+氯吡格雷二联治疗组(B组)、阿司匹林+氯吡格雷二联治疗组(C组)。最常用治疗方案是停用华法林钠,联用阿司匹林和氯吡格雷。3个治疗组患者的再梗死、死亡、脑血管意外、严重出血及输血治疗等差异无统计学意义。结论:高危血栓栓塞风险患者冠状动脉支架术后应予三联治疗,密切监测凝血酶原时间(PT)和国际标准化比值(INR);而对于低危血栓栓塞风险的患者停用华法林钠,联用阿司匹林和氯吡格雷的治疗方案是可行的。本项调查观察样本量小,证据不够充分。针对不同患者制定相应的抗栓治疗方案,才能在获得良好抗栓疗效的同时减少出血事件。     

冠心病合并房颤的老年患者PCI术后抗栓治疗的安全性和有效性

目的比较华法林联合阿司匹林、氯吡格雷和华法林联合替格瑞洛在冠心病合并房颤的老年患者PCI术后抗栓治疗中的安全性和有效性。方法 207例符合特定条件的PCI术后冠心病合并房颤的老年患者随机分成两组,对照组(n=103)为华法林+阿司匹林(100 mg/d)+氯吡格雷(75 mg/d)三联抗栓6个月,之后改为华法林+氯吡格雷(75 mg/d)或阿司匹林(100 mg/d)抗栓至12个月,试验组(n=104)为华法林+替格瑞洛(90 mg/d,2次/d)双联抗栓6个月,之后改为华法林+替格瑞洛(60 mg,2次/d)抗栓至12个月,两组均给予其他规范药物治疗方案。比较两组患者12个月内出现的主要心血管不良事件(MACE)及出血事件。结果两组MACE事件、出血事件差异比较均无统计学意义(P>0. 05)。结论对于PCI术后冠心病合并房颤的老年患者12个月华法林联合替格瑞落和华法林联合阿司匹林、氯吡格雷的抗栓效果相似,且出血风险未增加,提示本研究中华法林联合替格瑞洛双联抗栓策略安全有效。     

世界心脏病学大会(WCC)2010——华法林依然是心房颤动抗凝的基石

心房颤动(房颤)氯吡格雷和厄贝沙坦预防血管事件研究-阿司匹林(ACTIVE-A)和房颤氯吡格雷和厄贝沙坦预防血管事件研究-华法林(ACTIVE-W)虽已经落幕,但对于不适宜华法林抗凝的房颤患者(甚至无华法林禁忌的房颤患者)是否应以双联抗血小板(阿司匹林+氯吡格雷)替代尚未达成共识.     

不同抗栓策略在老年急性NSTEMI合并房颤中的效果及安全性

目的针对不同抗栓策略在老年急性NSTEMI合并房颤中的效果及安全性进行探讨。方法随机选择2010年3月~2013年3月,我院收录的100例老年急性NSTEMI合并房颤患者作为本次研究的对象,将其平均分为4组:A组、B组、C组、D组。A组患者的治疗方法为阿司匹林+氯吡格雷,B组的治疗方法为华法林,C组的治疗方法为华法林+阿司匹林或者氯吡格雷,D组的治疗方法为华法林+阿司匹林+氯吡格雷。对4组患者的治疗效果以及治疗安全性进行对比分析。结果 4组患者的不同治疗方法的治疗死亡率分别为12.00%、20.00%、12.00%、8.00%。对所有患者观察1年,因为心血管疾病再次入院的24.00%,因出血再次入院的有12.00%。4组患者发生的心血管疾病无较大的差异性,但是D组患者的出血风险最高,C组的风险相对较低。结论针对老年急性NSTEMI合并房颤的治疗,虽然华法林+阿司匹林+氯吡格雷的死亡率最低,但是其出血风险较高,华法林+阿司匹林或者氯吡格雷的死亡率虽然高于D组,但是其风险最低。所以在老年急性NSTEMI合并房颤治疗中,采用华法林+阿司匹林/氯吡格雷治疗,风险较低。     

ACS合并糖尿病患者药物涂层支架术后应用新型三联抗血小板治疗的长期疗效

目的:探讨新型三联抗血小板治疗急性冠状动脉综合征(ACS)合并糖尿病(DM)患者药物涂层支架术后的长期疗效。方法:收集245名在我院进行经皮冠状动脉介入治疗的ACS合并DM患者资料,按照手术后不同治疗方案分为:二联抗血小板组(124例,阿司匹林和氯吡格雷联合治疗)和三联抗血小板组(121例,阿司匹林,氯吡格雷和西洛他唑联合治疗),1年后对两组治疗的远期效果进行比较。结果:1年后,三联抗血小板组主要不良心脏事件发生率明显低于二联抗血小板组(8.3%比17.7%,P=0.028);两组患者支架内血管再狭窄和不良反应发生率均无显著差异(P均0.05),且均没有出现严重的出血事件。结论:急性冠脉综合征合并糖尿病患者行药物涂层支架手术后采用阿司匹林,氯吡格雷和西洛他唑的三联抗血小板治疗,可显著降低主要不良心脏事件发生率,并且与采用阿司匹林,氯吡格雷的二联抗血小板治疗方案相比,并未增加药物不良反应发生率,值得推广。     

阿司匹林、氯吡格雷和华法令三联抗栓方案在冠心病治疗中的应用

冠心病支架植入术后患者常规需要接受阿司匹林、氯吡格雷的双联抗血小板治疗,而当上述患者同时存在心房颤动、左心室血栓等抗凝治疗指征时,常常需要选择阿司匹林、氯吡格雷和华法令的三联抗栓治疗方案.然而,该治疗方案常伴随着显著的出血风险,其安全性、有效性、必要性等问题长期困扰着临床医师,也是当前研究者争论的一大热点问题.文章通过复习近年来的文献报道,对三联抗栓治疗在冠心病患者中的应用作一综述.     

Combination therapy with aspirin, clopidogrel and warfarin following coronary stenting is associated with a significant risk of bleeding

Dual antiplatelet therapy of aspirin and a thienopyridine is the standard of care following coronary stenting. Patients who are on chronic warfarin therapy and receive a coronary stent need to be treated with the triple therapy of aspirin, clopidogrel and warfarin; however, the bleeding risk in these patients is unknown. To evaluate the bleeding risk in patients requiring chronic warfarin therapy and undergoing stent implantation, we compared 107 consecutive patients on chronic warfarin therapy who underwent coronary stenting and were discharged on aspirin, clopidogrel and warfarin to 107 contemporary patients who were treated with aspirin and clopidogrel. We evaluated their bleeding history before and after coronary stenting. Major bleeding was defined as bleeding that was significantly disabling, intraocular or requiring at least 2 units of blood transfusion. Minor bleeding was defined as other bleeding that led to interruption of the medications. Patients on triple therapy were younger and more likely to have hypertension. This group had significantly higher major bleeding (6.6% vs. 0%; p = 0.03) and minor bleeding (14.9% vs. 3.8%; p = 0.01) compared with the dual antiplatelet therapy group. In the triple therapy group, the international normalized ratio or aspirin dosage did not influence the bleeding risk. In patients requiring warfarin therapy, the addition of dual antiplatelet therapy is associated with an approximately 7% major bleeding risk. Thus, novel regimens are needed to reduce the bleeding risk.     

Aspirin and clopidogrel with or without phenprocoumon after drug eluting coronary stent placement in patients on chronic oral anticoagulation

Objectives. Optimal antithrombotic/anticoagulation therapy in patients on chronic oral anticoagulation (OAC) undergoing drug‐eluting stent (DES) implantation is unknown. We investigated the efficacy and safety of two regimens of antithrombotic/anticoagulation therapy in patients who present for DES implantation whilst on OAC. Methods. We included a series of 515 patients on OAC who underwent DES implantation between 2002 and 2007. Based on predefined clinical and echocardiographic criteria, 306 patients continued OAC (triple therapy) and 209 patients discontinued OAC (dual therapy) for the time they received antiplatelet therapy with clopidogrel and aspirin [stent‐related antithrombotic treatment (SRAT)]. The primary end point was a composite of death, myocardial infarction, stent thrombosis or stroke. Results. During SRAT the primary endpoint was observed in 13 patients in the group with triple therapy versus 15 patients in the group with dual therapy [Kaplan–Meier estimates 4.2% and 7.2%, odds ratio (OR) = 0.61, 95% confidence interval (CI) 0.29–1.28; P = 0.19]. At 2 years of follow‐up, the primary endpoint was observed in 35 patients in the group with triple therapy versus 36 patients in the group with dual therapy (Kaplan–Meier estimates 14.1% and 18.0%, OR = 0.76, 95% CI: 0.48–1.21; P = 0.25). Two‐year incidence of major bleeding was 1.4% (n = 4, triple therapy) versus 3.1% (n = 6, dual therapy) (P = 0.34). Conclusions. In patients on chronic OAC undergoing DES implantation, clinical and echocardiographic criteria help to define postprocedural antithrombotic/anticoagulation therapy. Based on these criteria, both a double antiplatelet therapy (clopidogrel plus aspirin) and a triple therapy (OAC plus clopidogrel plus aspirin) are associated with favourable safety and efficacy.     

老年非瓣膜病性心房纤颤患者抗血栓治疗现状分析

目的分析空军总医院老年非瓣膜病性心房纤颤（NVAF）患者抗血栓药物治疗现状及未抗凝治疗的原因。方法调查老年NVAF患者109例,对其病因、血栓栓塞危险因素、抗血栓药物应用情况及未应用华法林抗凝治疗原因进行分析。应用CHADS卒中风险评分表对NVAF患者进行血栓栓塞危险评估。结果91.6%患者接受了抗血栓治疗。符合抗凝治疗指征患者68例,仅38.2%接受了华法林治疗,57.4%进行了抗血小板治疗阿司匹林剂量为（87±15）mg/d,4.4%未进行任何抗血栓治疗。而其中NVAF呈阵发性者仅5.0%应用了华法林抗凝治疗。未抗凝治疗者54例,其中存在抗凝禁忌证12例（15.0%）;严重出血而停用1例（1.3%）,不能凝血监测2例（2.5%）;担心出血拒绝8例（10.0%）;阵发性心房纤颤未抗凝治疗20例（25.0%）;冠脉支架术后双重抗血小板治疗而未抗凝治疗3例（3.75%）;原因不明9例（11.3%）。结论老年NVAF患者抗血栓治疗中华法林应用率低,而且阵发性心房纤颤的华法林应用率更低,抗血小板治疗中阿司匹林剂量不足。     

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.     

Drug insight: antithrombotic therapy after percutaneous coronary intervention in patients with an indication for anticoagulation

Antiplatelet therapy with aspirin and clopidogrel is standard care following revascularization by percutaneous coronary intervention with stent insertion. This so-called dual therapy is recommended for up to 4 weeks after intervention for bare-metal stents and for 6-12 months after intervention for drug-eluting stents. Although it is estimated that 5% of patients undergoing percutaneous coronary intervention require long-term anticoagulation because of an underlying chronic medical condition, continuing treatment with triple therapy (warfarin, aspirin and clopidogrel) increases the risk of bleeding. In most patients triple antithrombotic therapy seems justified for a short period of time. In some patients, however, a more considered judgment based on absolute need for triple therapy, risk of bleeding and risk of stent thrombosis is required, but the optimum antithrombotic treatment for these patients who require long-term anticoagulation has not been defined. This Review summarizes the existing literature concerning antithrombotic therapy and makes recommendations for initiation and duration of triple therapy in the small proportion of patients already receiving anticoagulant therapy who require percutaneous coronary intervention.     

Periprocedural and medium-term antithrombotic strategies in patients with an indication for long-term anticoagulation undergoing coronary angiography and intervention

OBJECTIVES: The optimal antithrombotic treatment for patients on long-term anticoagulation undergoing invasive coronary procedures is currently undefined. The strategies adopted periprocedurally and medium-term after coronary stenting (percutaneous coronary intervention with stent implantation) at our Institution, were reviewed, and the safety and efficacy of the various regimens evaluated. METHODS: All patients undergoing invasive coronary procedures between January 2002 and December 2004 were retrospectively identified. RESULTS: Out of 3709 patients overall, 104 (2.8%; 95% confidence interval 2.3-3.4) were on warfarin (because of atrial fibrillation in >50% of cases), whereas this was the case for 49 (3.1%; 95% confidence interval 2.3-4.1) of 1584 undergoing percutaneous coronary intervention with stent implantation. The antithrombotic strategies were highly variable, both periprocedurally (i.e. warfarin withdrawal or substitution by heparin, followed by aspirin with or without a thienopyridine) and medium-term after percutaneous coronary intervention with stent implantation (i.e. combination of warfarin and single or dual antiplatelet agents or pure dual antiplatelet treatment). Overall, periprocedural hemorrhages occurred in five patients (4.8%; 95% confidence interval 1.56-11.22). No thromboembolic events were observed, whereas one subacute stent thrombosis occurred (2%; 95% confidence interval 0.05-11) during warfarin and aspirin treatment. Among patients undergoing percutaneous coronary intervention with stent implantation, 1-month hemorrhagic rate was 10% (95% confidence interval, 3.3-23.8); most hemorrhages (major bleeds in three-quarters of cases) occurred during triple therapy with warfarin (or low-molecular-weight heparin), aspirin and a thienopyridine. CONCLUSIONS: At our Institution (where standardized protocols are currently not in use), periprocedural and medium-term antithrombotic treatment in patients on long-term anticoagulation undergoing percutaneous coronary intervention with stent implantation showed substantial variability. As a result of the relevant 1-month complication rate, further properly sized and designed studies are warranted to identify the optimal strategies for this patient subset, which is foreseen to progressively increase over the next years.     

Safety and efficacy of aspirin, clopidogrel, and warfarin after coronary stent placement in patients with an indication for anticoagulation

Background

Dual antiplatelet therapy with aspirin and clopidogrel has replaced aspirin and systemic anticoagulation with warfarin as the preferred antithrombotic therapy after percutaneous coronary intervention (PCI) with stent placement. However, a number of patients have indications for all 3 drugs. We sought to determine the frequency and type of hemorrhagic complications in patients who undergo systemic anticoagulation with warfarin while receiving aspirin and clopidogrel after a PCI with stent placement.

Methods

We performed a retrospective analysis of the Mayo Clinic PCI database and identified 66 consecutive patients who were discharged from hospital after PCI between January 2000 and August 2002 (inclusive) receiving a combination of dual antiplatelet therapy (aspirin and clopidogrel) and systemic anticoagulation (warfarin) to determine the incidence of bleeding and other clinical events during the treatment period.

Results

Six patients (9.2%; 95% CI, 3.5-19.0) reported a bleeding event; 2 patients required a blood transfusion. No patient died or sustained a myocardial infarction or stent thrombosis.

Conclusions

The risk of bleeding may be increased in patients treated with aspirin, a thienopyridine, and warfarin early after PCI with stent placement.     

Effects of triple antiplatelet therapy (aspirin, clopidogrel, and cilostazol) on platelet aggregation and P-selectin expression in patients undergoing coronary artery stent implantation

The purpose of this study was to determine the effect of the addition of cilostazol to aspirin plus clopidogrel on platelet aggregation after intracoronary stent implantation. Twenty patients who underwent coronary stent placement were randomly assigned to therapy with aspirin plus clopidogrel (dual-therapy group, n = 10) or aspirin plus clopidogrel plus cilostazol (triple-therapy group, n = 10). A loading dose of clopidogrel (300 mg) and cilostazol (200 mg) was administered immediately after stent placement, and clopidogrel (75 mg/day) and cilostazol (100 mg twice daily) were given for 1 month. Platelet aggregation in response to adenosine diphosphate (ADP; 5 and 20 micromol/L) or collagen and P-selectin (CD-62P) expression was assayed at baseline, 2 hours, 24 hours, 1 week, and 1 month after stent placement. Inhibition of ADP-induced platelet aggregation was significantly higher in patients receiving triple therapy than those receiving dual therapy from 24 hours after stent placement, and inhibition of collagen-induced platelet aggregation was significantly higher in the triple-therapy group beginning 1 week after stent placement. P-Selectin expression was significantly lower in the triple-therapy than dual-therapy group at 1 week and 30 days. In conclusion, compared with dual antiplatelet therapy, triple therapy after coronary stent placement resulted in more potent inhibition of platelet aggregation induced by ADP and collagen. These findings suggest that triple therapy may be used clinically to prevent thrombotic complications after coronary stent placement.