Triple antiplatelet therapy vs. dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: an evidence-based approach to answering a clinical query

AIMS

Outcomes of patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and bare metal stents (BMS) have not been evaluated separately for specific dual and triple antiplatelet agent use. The purpose of this meta-analysis was to determine whether triple antiplatelet therapy (combination of clopidogrel, aspirin and cilostazol) has any advantage in efficacy compared with standard dual antiplatelet therapy (aspirin and clopidogrel) in patients undergoing PCI.

METHODS

Electronic and printed sources were searched till May 2008 for randomized controlled clinical trials (RCTs) of cilostazol in combination with aspirin and clopidogrel. Pooled weighted mean difference (WMD) and pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated.

RESULTS

A total of four RCTs including 1457 patients with a median follow-up period of 6–9 months were included in the analysis. The rates of major adverse cardiac and/or cerebrovascular events (MACE/MACCE), stent thrombosis and bleeding were not significantly different between triple and dual antiplatelet therapy groups. Pooled analysis showed that cilostazol was associated with significantly decreased incidence of in segment restenosis (ISR) (OR 0.51, 95% CI 0.38, 0.68; P < 0.00001), increased minimum luminal diameter (MLD) (WMD 0.16, 95% CI 0.10, 0.22; P < 0.00001) for both DES and BMS and also individually. However, the rates of target vessel revascularization (OR 0.45, 95% CI 0.25, 0.83; P = 0.01 and late lumen loss (pooled WMD 0.14, 95% CI 0.2, 0.07; P = 0.001) were decreased significantly only in the DES group receiving triple therapy.

CONCLUSIONS

Cilostazol appears to be effective in reducing the rates of ISR without any significant benefit for MACE/MACCE.     

Effects of pantoprazole on dual antiplatelet therapy in stable angina pectoris patients after percutaneous coronary intervention

BackgroundOur aim was to prospectively assess the potential influence of pantoprazole therapy on the antiplatelet effects of acetylsalicylic acid (ASA) and clopidogrel (CLO) in stable angina pectoris (SAP) patients after percutaneous coronary intervention (PCI).MethodsForty-four patients with SAP (CCS I-III) and successful PCI with stent implantation were enrolled into the study. The patients were divided into group proton pump inhibitors (PPI): 23 patients with indications for PPI (F/M = 9/14; age = 64 ±  9; standard therapy + 20 mg pantoprazole) and the control group (group C): 21 patients (F/M = 6/15; age = 64 ±  8; standard therapy). The platelet function analysis in whole blood based on impedance aggregometry (ASPI, COL, ADP, TRAP tests) using Multiplate – V2.02.11 was performed 18–24 h after the PCI + CLO loading dose (600 mg) and 30 days after PCI.ResultsBoth baseline patient characteristics and clinical outcomes were comparable between the study groups. There were no differences in the mean values of the platelets (PTL) tests measured at the 30^th day after PCI between both groups (PPI vs. C: ASPI: 24.6 ±  10.0 vs. 42.1 ±  14.8U, COL: 32.9 ±  8.6 vs. 34.0 ±  7.7U, ADP: 26.8 ±  12.4 vs. 30.4 ±  8.1U, TRAP: 78.7 ±  16.6 vs. 78.1 ±  22.6U, p = ns). The mean delta values of the PTL tests (18–24 h post-PCI/30 days post-PCI) were also comparable between the groups. The PTL aggregometry results were related to time (ADP, ASPI, TRAP vs. time, p = 0.001; COL vs. time, p = 0.03) – the baseline values of ADP, ASPI, COL and TRAP tests were smaller than those measured after the one-month observation.ConclusionsPantoprazole treatment does not impair the efficacy of dual antiplatelet therapy in patients with SAP after PCI.     

Risk of major bleeding with concomitant dual antiplatelet therapy after percutaneous coronary intervention in patients receiving long-term warfarin therapy

STUDY OBJECTIVES: To characterize the safety of concomitant aspirin, clopidogrel, and warfarin therapy after percutaneous coronary intervention (PCI), and to identify patient characteristics that increase the risk of hemorrhage. DESIGN: Retrospective, matched cohort study. SETTING: Academic medical center and affiliated outpatient offices. PATIENTS: The active group consisted of 97 patients who underwent PCI from January 1, 2000-September 30, 2005, and received warfarin, aspirin, and clopidogrel; the control group consisted of 97 patients who were individually matched to patients in the active group by procedure type, procedure year, age, and sex. Control patients received aspirin and clopidogrel. MEASUREMENTS AND MAIN RESULTS: Clinical data were collected from inpatient records, outpatient physician office records, and telephone surveys administered to patients or caregivers. The primary end point was major bleeding. The median duration of follow-up after index procedure was 182 days (range 0-191 days) in the active group and 182 days (range 0-213 days) in the control group. Fifty-seven (59%) of the 97 patients in the active group received warfarin for atrial fibrillation. There were 14 major bleeds in the active group (including 1 death) and 3 major bleeds in the control group during the study period. Mean international normalized ratio at the time of bleeding was 3.4. Hazard ratio for major bleeding was 5.0 in patients receiving warfarin therapy (95% confidence interval 1.4-17.8, p=0.012). Aspirin dose, age, sex, body mass index, history of hypertension, diabetes mellitus, intraprocedural glycoprotein IIb-IIIa or anticoagulant type, and postprocedural anticoagulant use did not have a significant effect on the risk of major bleeding. CONCLUSION: Warfarin was an independent predictor of major bleeding after PCI in patients receiving dual antiplatelet therapy. Prospective data to further characterize the safety of concomitant warfarin and dual antiplatelet therapy after PCI are needed.     

冠脉介入干预治疗前后抗凝和抗血小板治疗

急性冠脉综合征（ACS）发病机制为冠脉内动脉粥样硬化斑块不稳定、破裂而导致斑块表面血小板黏附、激活、释放相关因子．血小板聚集形成血栓,同时．激活外源性凝血机制通路．形成凝血瀑布,而形成血栓。对于ACS．无论是ST段抬高急性心肌梗死．     

糖尿病合并冠心病患者经皮冠状动脉介入术后三联抗血小板治疗的效果及安全性研究

目的观察糖尿病合并冠心病患者经皮冠状动脉介入（PCI）术后三联抗血小板治疗的临床效果及安全性。方法将166例糖尿病合并冠心病患者按随机数字表分为对照组（80例）和观察组（86例）,对照组给予阿司匹林100mg／d、氯吡格雷75mg／d;观察组在双联基础上加西洛他唑100mg／d。记录分析2组基线资料、冠状动脉造影和PCI的结果差异,随访观察2组主要终点和次要终点事件发生率的差异。,结果术后随访观察组最小管腔直径明显高于对照组[（2．76±0．53）mm比（1．35±0．32）ml／1,P〈0．05];观察组管腔晚期丢失和再狭窄率均明显低于对照组[（1．28±0．33）mm比（0．71±0．23）mm,2．3％（2／86）比11．2％（9／80）,均P〈0．05]。随访1个月及1年,观察组主要终点事件发生率明显低于对照组,差异有统计学意义[1个月：2．3％（2／86）比8．8％（7／80）,P〈0．05;1年：5．8％（5／86）比11．2％（1／80）,P〈0．05];次要终点发生率比较差异无统计学意义[1个月：1．16％（2／86）比1．25％（1／80）;1年：2．3％（2／86）比2．5％（2／80）,P〉0．05]。结论PCI术后预防支架内再狭窄患者氯吡格雷、阿司匹林和两洛他唑三联抗血小板治疗,疗效确切,可进一步降低主要不良心脑血管事件的发生率,同时并不增加出血风险。     

经皮冠脉介入治疗术后双联抗血小板治疗预后的影响因素分析

目的:进行冠心病患者经皮冠脉介入治疗(percutaneous coronary intervention,PCI)术后服用阿司匹林和氯吡格雷双联抗血小板治疗(dual antiplatelet therapy,DAPT)预后的影响因素分析,以明确术后患者接受DAPT治疗后发生不良事件的可预测因素,为冠心病临床治疗提供依据。方法:回顾性纳入2015年4月至2016年6月于北京大学第一医院行PCI手术的冠心病患者,收集患者的人口学资料、疾病史及实验室检查,并于术后1.5年进行随访,记录患者在此期间患者出血、血管内皮增生、支架内再狭窄(in-stent restosis,ISR)以及再次植入支架的发生情况。采用单因素与多因素Logistic回归分析探讨DAPT治疗预后的独立影响因素,并建立列线图预测模型。结果:纳入的139例患者中,未发生组95人,发生组44人。多因素Logistic回归分析显示年龄、DAPT满1年、D-dimer水平和LDL是双联抗血小板治疗预后的独立影响因素。建立列线图风险预测模型,其ROC曲线下面积(AUC)为0.762。Hosmer-Lemeshow拟合优度检验χ²=8.645,P=0.373,预测模型有较好的校准能力。结论:年龄、DAPT满1年、D-dimer水平和LDL是双联抗血小板治疗预后的独立影响因素,列线图模型预测效能较好。     

Current strategies with eptifibatide and other antiplatelet agents in percutaneous coronary intervention and acute coronary syndromes

Antiplatelet and anticoagulation therapies are essential for the prevention of thromboembolic-induced myocardial ischaemia in non-ST-elevation acute coronary syndromes and the ischaemic complications of percutaneous coronary intervention. Although heparin, direct thrombin inhibitors and oral platelet activation inhibitors provide substantial benefit, only glycoprotein (GP) IIb/IIIa inhibitors block the final common pathway leading to platelet aggregation, and the American College of Cardiology/American Heart Association guidelines recommend GP IIb/IIIa inhibitors as an integral component of care in these patients. Abciximab, eptifibatide and tirofiban all act through the GP IIb/IIIa receptor; however, variations in clinical outcomes among patients receiving these agents may be related to their structural and pharmacological differences, as well as to patient demographics. Data indicate that eptifibatide, at the current recommended dosing schedule, achieves the highest level of consistent platelet inhibition compared with current doses of abciximab and tirofiban.     

临床药师参与1例经皮冠状动脉介入术后血小板高反应患者的抗血小板治疗

目的:探讨临床药师在个体化抗血小板治疗中的作用。方法:回顾性分析临床药师参与的1例经皮冠状动脉介入术后再发缺血事件的抗血小板治疗的案例。结果:临床药师通过患者的疾病、基因型、药物相关作用等因素从药学角度分析再发缺血事件的原因,并参与药物治疗和药学监护,协助临床医生为患者制定个体化抗血小板治疗方案。结论:利用基因检测技术,临床药师为患者实施个体化抗血小板治疗,保障患者用药的安全、有效。     

Long-term clopidogrel therapy in patients receiving percutaneous coronary intervention

BACKGROUND: The PCI-CURE (Percutaneous Coronary Intervention-Clopidogrel in Unstable Angina to Prevent Recurrent Events) and CREDO (Clopidogrel for the Reduction of Events During Observation) studies have demonstrated that, in addition to aspirin, pre-treatment with clopidogrel followed by long-term (i.e. 9-12 months) therapy significantly reduces the risk of atherothrombotic events in patients undergoing percutaneous coronary intervention (PCI). OBJECTIVE: To examine the economic implications, from the Dutch healthcare perspective, of the use of clopidogrel in patients undergoing PCI (elective procedures or in patients with acute coronary syndrome), comparing pre-treatment followed by long-term therapy with only 4 weeks of treatment. METHODS: A lifetime Markov model was used to combine data from the PCI-CURE and CREDO trials with data from the literature concerning epidemiology, costs and quality of life. The model was run separately for each trial. Only direct healthcare costs (euro, year 2004 values) were considered. Costs and outcomes were discounted at 4% per anum. For each trial, the cost effectiveness is expressed as costs per life-year and QALY gained. Uncertainties are addressed by uni- and probabilistic multivariate sensitivity analysis. RESULTS: When starting with the data from the PCI-CURE trial, pre-treatment plus 9-month clopidogrel therapy was predicted to save 1119 euros and gain 0.03 life-years and 0.07 QALYs per patient compared with short-term treatment. When starting with the data from the CREDO trial, the combination of pre-treatment and prolonged clopidogrel therapy (1 year) was estimated to save 497 euros and gain 0.10 life-years and 0.14 QALYs per patient. Univariate and probabilistic multivariate sensitivity analyses suggested that the conclusions were generally robust, but that the expected gain in survival for the PCI-CURE population was very sensitive to the effects on mortality within the combined endpoint of myocardial infarction/stroke-free survival. CONCLUSIONS: In The Netherlands, pre-treatment plus long-term (9-12 months) therapy with clopidogrel is estimated to save costs and increase (quality-adjusted) survival in the prevention of ischaemic events among patients undergoing elective PCI (CREDO) and in patients with acute coronary syndrome (PCI-CURE) compared with short-term treatment with clopidogrel without pre-treatment.     

经皮冠状动脉介入治疗患者抗血小板药物抵抗的相关因素分析

目的分析经皮冠状动脉介入治疗(PCI)后的急性冠脉综合征(ACS)患者抗血小板药物治疗抵抗的发生率及临床危险因素。方法 381例行PCI治疗的ACS患者,根据血栓弹力图(TEG)血小板聚集抑制率(PAI)的结果将患者分组。ADP诱导的PAI(ADP-PAI)<30%为氯吡格雷抵抗(CR);AA诱导的PAI(AA-PAI)<50%为阿司匹林抵抗(AR)。对所有入组患者临床资料及常规生化指标进行回顾性分析。结果所有381例ACS患者均给予双重抗血小板治疗,其中72例(18.9%)为CR,30例(7.9%)为AR。多元回归分析结果显示,HDL和FBG与ADP-PAI呈显著负相关(r2=20.3%,P<0.05);糖尿病病程和hs-CRP与AA-PAI密切相关(r2=21.8%,P<0.05)。研究人群中,13例(3.4%)为双重抵抗(DR),76例(19.95%)是CR或AR的单一抵抗(SR)。糖尿病病程、FBG及Hb A1c在DR组显著高于SR及反应正常组(P<0.05)。对年龄及性别的研究显示,ADP-PAI在老年人及非老年人中无显著性差异,无论是男性还是女性(P>0.05);而老年女性的AA-PAI显著低于非老年女性(P<0.01)。老年女性较同龄男性ADP-PAI更低(P<0.05);而年轻女性AA-PAI较同龄男性明显升高(P<0.01)。结论 PCI术后的ACS患者,FBG及HDL升高是CR的高危因素;糖尿病病程长及高hsCRP水平的患者更容易发生AR。糖尿病病程长、血糖控制不佳患者更易发生2种抗血小板药物联合抵抗,这种患者相当危险。老年女性CR风险高于同龄男性,而年轻男性及老年女性发生AR的风险偏高。了解抗血小板治疗抵抗高危因素,对于高危患者,早期筛查、早期诊断、及时改变治疗方案可能是预防PCI术后血栓形成并发症的有效方法之一。     

Cost-effectiveness analysis of antithrombotic therapy in nonurgent percutaneous coronary intervention

STUDY OBJECTIVE: To perform a cost-effectiveness analysis comparing three treatment approaches during nonurgent percutaneous coronary intervention (PCI): bivalirudin with provisional glycoprotein (GP) IIb-IIIa inhibitor therapy, unfractionated heparin (UFH) with eptifibatide, and UFH with abciximab. DESIGN: Literature-based decision model from an institutional perspective. DATA SOURCE: Patient data from the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 study and three other randomized controlled trials that included UFH and routine GP IIb-IIIa inhibitor (eptifibatide or abciximab) therapy. All included studies were comparable based on patient population, procedural techniques, and general treatment approaches. MEASUREMENTS AND MAIN RESULTS: We included patient populations undergoing contemporary nonurgent PCI to identify probabilities of success or complications (myocardial infarction, urgent revascularization, thrombocytopenia, and major or minor bleeding at 30 days). Costs were assigned to each outcome by incorporating diagnosis-related group-- and/or Current Procedural Terminology--associated costs, institutional drug acquisition costs, and unit replacement costs of platelets and red blood cells. In the base-case analysis, the use of bivalirudin with provisional GP IIb-IIIa inhibitor therapy dominated the UFH and planned GP IIb-IIIa inhibitor approach: UFH with eptifibatide was 74 US dollars more expensive and 1.2% less effective, and UFH with abciximab was 777 US dollars more expensive and 2.3% less effective. Sensitivity analyses indicated that the model results were robust, but also revealed that bivalirudin lost its cost-effectiveness, resulting in UFH with eptifibatide becoming more cost-effective, when two or more vials of bivalirudin were necessary in greater than 27% of cases or when the use of provisional GP IIb-IIIa inhibitor therapy exceeded 20%. CONCLUSION: This analysis indicates that bivalirudin with provisional GP IIb-IIIa inhibitor therapy is the most cost-effective antithrombotic treatment strategy in nonurgent PCI when its use and dosing are consistent with the REPLACE-2 trial.     

急诊经皮冠状动脉介入治疗术后抗栓治疗个体化方案研究

目的探讨急性冠状动脉综合征患者经皮冠状动脉介入（PCI）后根据全血凝血检测值调整抗血小板治疗方案的安全性和有效性。方法收集行急性冠状动脉综合征急诊PCI患者中凝血速率〉23cP／min的48例患者进行试验,并将其完全随机分为对照组和优化组,各24例。对照组所有病例均采用标准阿司匹林、氯吡格雷二联抗血小板治疗,优化组在标准二联基础上加服西洛他唑1个月。观察2组主要终点事件和次要终点事件的发生率及不良反应发生率并加以比较。结果优化组治疗后凝血速率为（13．6±2．3）cP／min,明显低于治疗前[（25．3±1．6）cP／min,P〈0．01]。随访1年后优化组主要终点事件发生率为4．2％（1／24）,次要终点事件发生率为8．3％（2／24）;对照组主要终点事件发生率为16．7％（4／24）,次要终点事件发生率为37．5％（9／24）。2组主要终点事件发生率比较差异无统计学意义（P〉0．05）,次要终点事件发生率差异有统计学意义（P〈0．05）。优化组与对照组次要出血事件分别为1例（4．2％）和0例,轻微出血事件分别为3例（12．5％）和2例（8．3％）,差异均无统计学意义（均P〉0．05）。结论根据凝血速率检测结果调整抗血小板治疗可能有利于改善高凝状态急性冠状动脉综合征PCI患者的预后,但其有效性及安全性还需要大样本临床研究证实。     

经皮冠状动脉介入治疗术后患者合并情绪障碍的现况调查

目的分析经皮冠状动脉介入治疗术后患者精神抑郁的发病情况、主要特征和高危因素以及与预后的相关性。方法选择冠脉介入治疗术后患者128例和同年龄段对照组102例,采用Beck抑郁自评问卷(BDI-II量表)、患者健康状况问卷-9(PHQ-9量表)及DS14问卷进行调查。结果 PCI组、对照组的精神抑郁率分别为59.4%、10.8%,两组比较差异有统计学意义(P<0.05)。PCI组BDI-II评分明显高于对照组(P<0.05)。PCI组D型性格的发生率为78.1%。结论精神抑郁在冠脉介入术后患者中发生率高,对冠心病的发生、发展及预后有不良影响。D型性格易患抑郁。     

Dual antiplatelet therapy after coronary stenting

Introduction: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y₁₂ receptor inhibitor represents the mainstay of pharmacotherapy in patients undergoing coronary stenting. Currently, three P2Y₁₂ receptor inhibitors are approved for clinical use, including clopidogrel, prasugrel, and ticagrelor, with the latter two being preferred in patients presenting with an acute coronary syndrome. The introduction into clinical practice of newer-generation drug-eluting stent (DES) with safer profiles (i.e. less stent thrombosis) compared with earlier platforms have led recent guideline updates to re-evaluate the optimal duration of DAPT therapy, which are now based on evidence of a multitude of randomized clinical trials, registries, and meta-analysis and take into consideration the ischemic and bleeding risk profile of the patients.

Areas covered: Most recent updates on DAPT duration from professional societies in the United States and Europe are discussed. Moreover, an assessment of clinical trials, registries, and meta-analysis leading to changes on practice guidelines analyzed.

Expert opinion: The widespread introduction into clinical practice of newer-generation DES allows for shortening DAPT duration as also endorsed by practice guidelines. However, the optimal duration of DAPT therapy varies according to the individuals’ risk of ischemic and bleeding complications, with longer or shorter durations of treatment, respectively, that may be considered.     

Cangrelor in percutaneous coronary intervention

Cangrelor is a novel, intravenous P2Y₁₂ receptor antagonist in development for use in percutaneous coronary intervention. Currently in Phase III testing, the reversible platelet inhibitor provides several inherent advantages over other P2Y₁₂ receptor antagonists in this setting for the prevention of adverse cardiac events. Unlike the class of thienopyridines (ticlopidine, clopidogrel and potentially soon to be available, prasugrel), cangrelor has nearly immediate onset after a bolus dose and a short half-life, and achieves maximal inhibition of ADP-mediated platelet function. Cangrelor’s distinct mechanism of action allows for intravenous administration and avoids both hepatic and renal metabolism. These unique characteristics make cangrelor a promising agent for use in cardiovascular patients undergoing percutaneous coronary intervention.     

阿托伐他汀对经皮冠状动脉介入术患者心肌损伤的保护作用

目的 探讨阿托伐他汀对经皮冠状动脉介入术（ PCI）患者心肌损伤的保护作用.方法 285例行PCI患者随机分为观察组（n=140）和对照组（n=145）,两组均按PCI常规治疗,观察组PCI术前7d开始口服阿托伐他汀（40 mg/d）,对照组术前未服用他汀类降脂药.观察两组肌酸激酶同功酶-MB（CK-MB）、肌钙蛋白Ⅰ（TnI）水平变化情况.结果 观察组TnI及CK-MB峰值分别为（0.12±0.26） μg/L、（2.61±3.07）μg/L明显低于对照组的（0.51±1.14） μg/L、（6.85±14.38） μg/L（t=3.951、3.414,均P＜0.05）.结论 PCI术前1周采用阿托伐他汀治疗可减少PCI术后的心肌损伤.     

冠状动脉介入术后发生肝素诱导的血小板减少症抗栓治疗的药学监护

目的 探讨临床药师在急性心肌梗死（AMI）患者经皮冠脉介入术（PCI）后发生肝素诱导的血小板减少症（heparin-induced thrombocytopenia,HIT）抗栓治疗方案制定及药学监护。方法 临床药师利用急性冠脉综合征临床风险评分（GRACE）及抗血小板、抗凝治疗出血风险评分（Crusade）进行死亡风险及缺血、出血风险评估,及时调整抗栓治疗方案。出现HIT后分析血小板减少的原因及凝血功能,确定可能的相关药物因素,选择阿加曲班替代抗凝治疗,并及时监测活化部分凝血活酶时间（APTT）进行剂量调整。从药物的作用机制,不良反应,安全经济性,阐述出院带药选择华法林对患者的用药优势。结果 选择阿加曲班替代抗凝治疗,维持双联抗血小板（阿司匹林+氯吡格雷）方案,患者情况控制平稳,未出现出血及血栓栓塞并发症,顺利出院。结论 临床药师需要充分了解药理学及药动学变化,可协助临床发现药物治疗相关问题。同时需加强监测,以便及时调整用药方案,提高临床用药的安全性和合理性,为患者提供更好的药学服务。     

负荷量瑞舒伐他汀对冠心病PCI术后预后的影响

目的 探讨负荷量瑞舒伐他汀钙对经皮冠脉介入治疗（PCI）围手术期心肌损伤发生率及PCI术后1年预后的影响.方法 91例接受择期PCI的冠心病（包括稳定型心绞痛和不稳定型心绞痛）,根据是否给予负荷量瑞舒伐他汀分为负荷量组和对照组,通过监测术后高敏肌钙蛋白水平,前瞻性观察两组患者围手术期心肌损伤的发生率及PCI术后1年主要心脏不良事件（major adverse cardiac events,MACE）发生率.结果 负荷量组术后围手术期心肌损伤的发生率（46.7％vs87.0％,P＜0.001）和围手术期心肌梗死的发生率（11.1％vs 37.0％,P=0.006）明显低于对照组,但总MACE发生率在两组患者未有统计学差异（2.2％ vs 8.7％,P=0.361）.结论 PCI术前给予负荷量的瑞舒伐他汀可减少围手术期心肌损伤的发生,但对PCI术后1年MACE事件的发生率未有明显影响.