Dual antiplatelet therapy with or without oral anticoagulation in the postdischarge management of acute coronary syndrome patients with an indication for long term anticoagulation: a systematic review

Currently, there is a lack of consensus among guidelines for the postdischarge treatment of patients presenting with acute coronary syndrome (ACS) who have a long-term indication for anticoagulation. We conducted a systematic review comparing the safety and effectiveness of dual antiplatelet therapy (DAPT) and triple therapy (TT; defined as DAPT plus an oral anticoagulant) in patients with ACS and a long-term indication for anticoagulation. We searched for clinical studies in MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews published between January 1995 and September 2013. Each investigator screened and abstracted data, assessed applicability and quality, and graded the strength of evidence. Meta-analysis of direct comparison was performed when outcomes and follow-up periods were comparable. Fourteen observational studies were identified that contained comparative effectiveness data on DAPT versus TT. No difference in the odds of mortality (OR 1.04, 95 % CI 0.59–1.83) or stroke (OR 1.01, 95 % CI 0.38–2.67) at 1–5 years was found between TT and DAPT. Major bleeding at 1–5 years (OR 1.46, 95 % CI 1.07–2.00) and nonfatal MI at 1–5 years (OR 1.85, 95 % CI 1.13–3.02) occurred more frequently in patients receiving TT. The results of this systematic review demonstrate that treatment with TT was associated with increased rates of nonfatal MI and major bleeding when compared with treatment with DAPT in the postdischarge management of ACS patients with an indication for oral anticoagulation. Until results of ongoing randomized trials assessing antithrombotic therapies define optimal management strategies, the current analysis suggests using caution when prescribing TT to these patients.     

Dual versus single antiplatelet therapy for patients with long-term oral anticoagulation undergoing coronary intervention: A systematic review and meta-analysis

Objective The main aim of this meta-analysis is to compare the efficacy and safety of dual versus single antiplatelet therapy for patients taking oral anticoagulation (OAC) after coronary intervention. Background The optimal regimen remains controversial patients taking OAC after coronary intervention. Methods PubMed, Embase and Cochrane Central Register of Controlled Trials were searched for eligible studies including data of triple therapy (TT) versus OAC plus single antiplatelet therapy for patients requiring OAC after coronary intervention. The primary outcome was major adverse cardiac and cerebrovascular event (MACCE). The safety outcome was major bleeding. Results Fourteen studies with 32825 patients were included. Among prospective studies, patients with TT had a trend toward a higher risk of major bleeding [odds ratios (OR): 1.56, 95% confidence interval (CI): 0.98–2.49, P = 0.06] and a markedly higher risk of all-cause death (OR; 2.11, 95% CI: 1.10–4.06 P = 0.02) compared with OAC plus clopidogrel. Meanwhile, TT was associated with decreased risks of MACCE (OR: 0.63, 95% CI: 051–0.77 P < 0.0001), all-cause death (OR: 0.45, 95% CI: 0.20–0.97, P = 0.04), and stroke/transient ischemic attack (TIA)/peripheral embolism (PE) (OR: 0.29, 95% CI: 0.09–0.96, P = 0.04) compared with OAC plus aspirin.     

Comparing anticoagulation therapy alone versus anticoagulation plus single antiplatelet drug therapy after transcatheter aortic valve implantation in patients with an indication for anticoagulation: a systematic review and meta-analysis

Cardiovascular Drugs and Therapy - This meta-analysis compared the efficacy and safety of oral anticoagulation (OAC) therapy alone versus OAC plus single antiplatelet therapy (SAPT) in patients...     

Long-term management of post acute coronary syndrome with oral antiplatelet therapy

Cardiovascular disease is the primary cause of early death and morbidity in the industrialized world and is becoming a growing problem in many developing countries. Coagulation inhibitors play a major role in the management of the acute phase of ACS whether in association with reperfusion strategies or not. Currently, and in accordance with the results of major randomised studies, for medium and long-term management, the association of Clopidogrel and aspirin is the treatment of choice. However, despite the recognised benefits of this therapeutic strategy and above all the recommendations of learned societies, which have placed this bi-therapy in class I, according to national and international registries it is still underused. Moreover, all of these registries have confirmed, in the real world, the negative impact of not prescribing this antiplatelet therapy on morbidity and mortality after both ST and non-ST elevation acute coronary syndrome. which shows the difficulty of applying to everyday clinical practice the results of major randomised cohorts.     

Antiplatelet therapy for postdischarge medical management of acute coronary syndrome

Postdischarge management of patients with acute coronary syndrome is often suboptimal, despite their high risk of a subsequent event. Updated American College of Cardiology/American Heart Association guidelines emphasize the need for aggressive modification of risk factors and treatment with antiplatelet, antihypertensive, and lipid-lowering agents commenced in-hospital and continued long-term. Antiplatelet therapy involving aspirin and clopidogrel is the mainstay of secondary risk reduction. Increased adherence to medication and risk factor modification at discharge has been demonstrated with acute care quality improvement initiatives. Extension of these initiatives to postdischarge care will provide data on medication adherence post acute coronary syndrome and functional outcomes in the community setting. Successful secondary prevention of cardiovascular events requires implementation of evidence-based guidelines by physicians, and adherence to pharmacotherapy and lifestyle modifications by patients. Primary care physicians are well placed to influence adherence through their ongoing relationships with patients and can save lives by implementing secondary risk reduction measures after discharge.     

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。     

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.     

Dynamic platelet adhesion in patients with an acute coronary syndrome: The effect of antiplatelet therapy

Platelet adhesion and aggregation are key functions leading to thrombus formation. The effect of aspirin, clopidogrel, and ticagrelor on platelet aggregation has been well established, however, there is limited data on the effect of these drugs on platelet adhesion. We therefore evaluated the effect of these drugs on platelet adhesion in acute coronary syndrome (ACS) patients. Citrated blood was collected from 50 ACS patients loaded with 325 mg of aspirin (baseline) and at 5 days after the administration of aspirin 100 mg/day and clopidogrel (600 mg loading dose, 75 mg/day) (n = 26) or ticagrelor (180 mg loading dose, 90 mg × 2/day) (n = 24). High on-treatment platelet reactivity (HTPR) to clopidogrel was estimated by vasodilator stimulated phosphoprotein (VASP) phosphorylation assay. Platelet adhesion to collagen was studied for 6 min under high shear stress and was evaluated using the time to platelet recruitment (TPR), the perimeter and average area of each adherent object, number of adherent objects, and the total percent of surface coverage (SC%). Six ACS patients exhibited HTPR to clopidogrel and excluded from the platelet adhesion assays. TPR and SC% values were similar among patient groups at baseline and controls. However, all other adhesion parameters were different in ACS patients, indicating the formation of more aggregates in regard to controls. At 5 days post-treatment with either clopidogrel or ticagrelor, the TPR values were increased and the SC% values were reduced to a similar extent compared with baseline. However, significant differences were observed in the ticagrelor group in the perimeter, number of adherent objects, and the average area of each adherent object indicating a more potent inhibition of adherence-induced platelet aggregation than clopidogrel. In conclusion, aspirin does not affect platelet adherence to collagen, whereas clopidogrel and ticagrelor inhibit to a similar extent dynamic platelet adhesion at 5 days post-treatment in ACS patients. However, ticagrelor exhibits a greater inhibitory effect on reducing adhesion-induced platelet aggregation.     

抗血小板疗法在老年急性冠脉综合征的临床应用

虽然大多数抗血小板疗法治疗急性冠脉综合征（ACS）的临床试验证实有显著临床效益,但老年患者,特别是≥75岁患者,仅少数有效,多数疗效欠佳,而出血风险增加。本文对因老龄化导致的止血血栓与出血的病理生物学,血管修复与整合作用变化,以及ACS抗血小板疗法在近年来临床试验中老年患者的效益与风险进行讨论。     

Optimal dual antiplatelet therapy strategy in elderly patients with acute coronary syndrome

One out of three hospitalizations for acute coronary syndrome (ACS) involve nowadays elderly patients, carrying together a significant burden of comorbidities and a higher risk of complications. In particular, both ischemic and haemorrhagic risk are markedly enhanced in advanced age, and strictly interconnected, challenging the management of dual antiplatelet therapy (DAPT) in these patients. The recent development of several therapeutic options in terms of duration and combination of antiplatelet agents have offered a wider spectrum of opportunities for a more individualized approach in the management of DAPT after an ACS, although the criteria for the selection of the most appropriate strategy in each patient still lack validation. In particular, dose-adjustment, early aspirin discontinuation, laboratory-driven tailoring and shorter or extended DAPT have been addressed with promising safety and efficacy results. The present review provides an updated overview on the emerging evidencefrom randomized clinical trials and subanalyses dedicated to the management of DAPT in elderly patients presenting with ACS.

Elderly patients, consideredas subjects above 75 years of age, currently account for over one third of the population being treated for acute coronary syndrome (ACS), and certainly the most challenging ones.^[1]In fact, age represents per se a major determinant of cardiovascular risk, being furthermore associated to a higher prevalence of other established risk factors, more complex anatomy and clinical condition, with increased comorbidities and frailty, accounting for the poor outcome results achieved in this particular subset of ACS patients.^[2-7]Despite medical management is still preferred in a large proportion of elderly patients, for the fear of periprocedural complications or the potential restraints to the use of dual antiplatelet therapy in patients undergoing percutaneous revascularization, several studies have demonstrated the prognostic advantages of an invasive approach and ad-hoc percutaneous coronary intervention (PCI) even in extremely advanced age.^[8-10]Moreover, the pivotal role of dual antiplatelet therapy in the management of ACS has been documented even in medically managed patients, thus further reinforcing the need to identify appropriate criteria for optimizing antiplatelet strategies, tailored according to patients’ characteristics and risk profile.     

替格瑞洛联合阿司匹林用于经皮冠状动脉介入术后长期抗血小板治疗的安全性观察

目的:探讨中国急性冠状动脉综合征(ACS)患者经皮冠状动脉介入治疗(PCI)后,使用替格瑞洛治疗1年的出血风险及危险因素。方法:纳入北京安贞医院2014年1月至2014年6月,ACS并成功完成PCI手术并接受阿司匹林联合替格瑞洛治疗的患者275例。记录患者的疾病类型、年龄、性别、体质量、HBG、血肌酐值、肌酐清除率、高血压病史、糖尿病史、消化道出血史及脑卒中史等,术后记录是否联用糖蛋白IIb/IIIa受体拮抗剂、是否联用质子泵抑制剂(PPI)等。所有患者均接受阿司匹林(100mg,1次/d)及替格瑞洛(90mg,2次/d)治疗1年。主要终点事件为:1年内PLATO标准的非冠状动脉旁路移植术(CABG)相关总出血的发生率。根据随访结果,将患者分为出血组和非出血组,对可能影响出血的因素进行单因素分析及Logistic回归分析。结果:替格瑞洛抗血小板治疗1年的非CABG相关总出血的发生率为13.5%,非CABG相关大出血发生率为5.5%;颅内出血的发生率为1.5%,致死性颅内出血发生率为0.8%。经多因素二元Logistic回归分析显示,年龄(OR=1.068,95%CI:1.008~1.133,P=0.027)、CRUSADE评分41(OR=4.227,95%CI:1.132~15.786,P=0.032)及联用质子泵抑制剂(OR=0.373,95%CI:0.166~0.836,P=0.017)为出血的主要影响因素。结论:对于应用替格瑞联合阿司匹林治疗的ACS患者,年龄增加及CRUSADE评分41为出血的危险因素,而联用质子泵抑制剂是防止出血的保护因素。     

长期使用低分子量肝素对急性冠脉综合征患者凝血、纤溶和抗凝系统的影响

将62例急性冠脉综合征患者随机分为两组，分别给予常规治疗和在此基础上的低分子量肝素（LMWH）治疗30天。在治疗前后不同时期检测抗Xa因子活性，D－二聚体（D-dimer),血浆纤溶酶原，血浆组织型纤溶酶原激活物，血浆纤溶酶原激活物抑制物以及抗凝血酶Ⅲ等凝血，纤溶，抗凝方面的指标，观察临床症状以及不良反应情况。结果：MWH组抗Xa因子活性，部分激活的凝血酶原时间上升，D-dimer明显降低，且随用药时间的延长而逐渐降低。抗Xa因子活性的变化与D－dimer的变化显著相关。常规治疗组各指标均无显著变化。认为急性冠脉综合征患者长期使用LMWH抗凝治疗，可有效改善患者高凝状态，且在必要的监测条件下安全性好。     

合并血小板减少的急性冠状动脉综合征患者经皮冠状动脉介入治疗和抗血小板治疗及随访

目的 探讨合并血小板减少的急性冠状动脉综合征（ACS）患者的临床特点、治疗及预后.方法 2012年3月至2013年3月北京友谊医院共完成PCI术1186例,有11例术前血小板低于100×10^9/L的ACS患者,占总例数的0.93％,回顾性分析11例患者的相关临床情况.结果 11例患者中,急性ST段抬高心肌梗死（STEMI）6例（54.5％）,非急性ST段抬高心肌梗死（NSTEMI）3例（27.3％）,不稳定型心绞痛（UAP）2例（18.2％）.5例（45.5％） STEMI患者行急诊PCI治疗,其余6例（54.5％）行择期PCI治疗.造影显示左主干＋三支血管病变3例（27.3％）,其余8例（72.7％）均为三支血管病变.术后随访（14.4±2.3）个月,期间3例（27.3％）发生出血并发症,3例（27.3％）发生主要不良心血管事件.结论 本组患者的冠状动脉病变以多支病变、复杂病变为主,临床预后不良.     

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.     

真实世界急性冠状动脉综合征或经皮冠状动脉介入治疗术后患者替格瑞洛抗血小板降阶治疗的临床转归

目的 探讨真实世界急性冠状动脉综合征(ACS)或经皮冠状动脉介入治疗(PCI)术后患者由替格瑞洛降阶为氯吡格雷抗血小板治疗的临床转归。方法 连续募集2013年10月至2016年8月于中国人民解放军总医院第一医学中心心血管内科住院期间接受替格瑞洛联合阿司匹林抗血小板治疗,并于住院期间或出院后1年内将替格瑞洛降阶为氯吡格雷的ACS或PCI术后患者746例。根据替格瑞洛降阶治疗时间,将患者分为急性期组(≤1个月,n=212)和非急性期组(1～3个月,n=262;3～6个月,n=156;6～12个月,n=116)。对所有患者进行1年随访。分析各组患者降阶治疗原因,比较各组患者主要终点事件[1年内净临床不良事件:全因死亡、非致死性心肌梗死、非致死性脑卒中、靶血管重建及出血学会研究会(BARC)定义的2、3、5型出血事件构成的复合终点事件]及次要终点事件(心血管缺血事件和BACR 2、3、5型出血事件)发生差异。采用SPSS 26.0软件进行统计分析。多因素logistic回归分析对比不同时间段行替格瑞洛降阶治疗后主要终点事件和次要终点事件的发生风险。结果 急性期组降阶治疗的主要原因是冠状动脉造影未见严重狭窄(23.1%),非急性期组降阶治疗的主要原因是无法获取替格瑞洛(41.9%)。急性期组1年内净临床不良事件发生率略高于非急性期1～3个月组,但差异无统计学意义(14.6% 和 12.2%;HR=0.72,95%CI 0.41～1.26;P=0.252)。非急性期1～3个月组的1年内净临床不良事件显著低于3～6个月组(12.2%和19.2%;HR=1.90,95%CI 1.07～3.37;P=0.029)及6～12个月组(12.2% 和21.6%;HR=1.48,95%CI 1.10～2.00;P=0.010)。各组间1年内心血管缺血事件比较,差异无统计学意义(P≥0.05)。非急性期1～3个月组的1年内出血事件显著低于6～12个月组(9.2%和15.5%; HR＝1.42,95%CI 1.01～2.00;P=0.044)。结论 真实世界中ACS或PCI术后患者在非急性期1～3个月内进行替格瑞洛抗血小板降阶治疗能够获得最佳的临床净获益。