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.     

冠心病介入抗栓治疗相关最新进展概要

近年经皮冠状动脉介入治疗（PCI）相关抗栓领域取得了许多关键性的进展。以TWILIGHT等研究为代表的降阶治疗探索是目前PCI术后抗血小板策略研究的主流方向之一,而在合并心房颤动PCI患者中,联合新型口服抗凝药物的双联或短程三联抗栓方案的有效和安全性已获多项新研究的印证。比伐芦定新的研究结果将更新直接PCI抗凝的循证证...     

PCI术后口服三联抗血小板治疗的有效性和安全性研究

目的评价PCI术后口服西洛他唑、阿司匹林、氯吡格雷三联抗血小板治疗的有效性和安全性。方法筛选成功行PCI术的冠心病患者150例,随机分成对照组（75例）和试验组（75例）。对照组至少于术后当日开始接受标准的阿司匹林和氯吡格雷两联抗血小板治疗,试验组亦至少于术后当日开始接受西洛他唑、阿司匹林和氯吡格雷三联抗血小板治疗。记录患者术后6个月主要心脏不良事件的发生及出血情况,采用血栓弹力图检测血小板聚集功能及药物抑制率。结果对照组、试验组术后6个月的主要心脏不良事件发生率分别为6．7％（5／75）和4．0％（3／75）,试验组低于对照组,但差异无统计学意义（P=0．467）;出血率分别为10．6％（8／75）和14。67％（11／75）,两组差异无统计学意义（P=-o．461）;两组术后6个月再次检测血栓弹力图,试验组结果更为理想,其MA值较对照组偏低,AA％、ADP％较对照组偏高,两组MA值、AA％、ADP％差异有统计学意义（P值均〈0．05）。结论PCI术后口服西洛他唑、阿司匹林和氯吡格雷三联抗血小板治疗不增加出血事件且可降低血小板聚集活性,提示三联抗血小板治疗可能有助于降低血栓发生风险。     

Drug insight: an overview of current anticoagulation therapy after heart valve replacement

Vitamin K antagonists, such as warfarin, are the gold standard approach for the long-term anticoagulant therapy of patients with mechanical heart valves. Management decisions are, however, based predominantly on expert consensus and on data from nonrandomized, follow-up studies, which have inherent limitations in their methods. Low-intensity anticoagulation therapy provides protection against thromboembolic complications in patients with most types of modern prosthetic heart valve. The addition of low-dose aspirin is safe if international normalized ratio values below 3.5 are maintained. A combined regimen should be considered in high-risk patients and those with coexistent coronary artery or cerebrovascular disease, and in patients who have suffered a thromboembolic event despite a therapeutic international normalized ratio. Thromboprophylaxis with unfractionated or low-molecular-weight heparins is restricted to specific situations, such as when a patient is intolerant to vitamin K antagonists, when surgical procedures require discontinuation of oral anticoagulation, or when the patient is pregnant. A lack of uniformity across practice guidelines make it difficult to reach treatment decisions. Each patient's preference, expressed after counseling about the risks and benefits of each treatment strategy, and an individual assessment of the patient's risk factors, should guide treatment decisions. At present, new anticoagulant agents such as factor Xa inhibitors do not represent a treatment option for heart valve recipients.     

Optimal antithrombotic treatment for percutaneous coronary intervention

Recent years have witnessed significant advances in the percutaneous treatment of patients with atherosclerotic vascular disease. Anti-platelet and anti-thrombotic agents are routinely administered to minimize the risk of peri-procedural myonecrosis, stent thrombosis and other procedural complications. This article presents a current view of optimal adjunctive antithrombotic therapy for percutaneous coronary interventions (PCI), recognizing that optimal is a necessarily subjective label. This article focuses specifically on anticoagulant agents such as unfractionated heparin (UFH), the low-molecular weight heparins (LMWH), and direct thrombin inhibitors, and antiplatelet agents, such as aspirin, thienopyridines, and glycoprotein IIb/IIIa antagonists. It starts with a general discussion of anticoagulation and percutaneous intervention, followed by a summary of the modern-day view of the coagulation process. The mechanism of action of the individual agents is then presented, followed by some of the evidence base of recent clinical trials of anticoagulant and antiplatelet agents in PCI. Finally, we present summary recommendations for procedural anticoagulation in low risk, not-low risk, and high risk PCI, and list what we feel are appropriate doses for the agents employed. Ultimately, though, it is the individual interventional cardiologists who must decide for themselves exactly what constitutes optimal antithrombotic therapy for PCI.     

Double antithrombotic therapy for prevention of bleeding and ischemic events after percutaneous coronary intervention in patients with atrial fibrillation: A meta-analysis

Background:The efficacy of double antithrombotic therapy (DAT) vs. triple antithrombotic therapy (TAT) for prevention of bleeding and ischemic events in patients with atrial fibrillation following percutaneous coronary intervention (PCI) is unclear in those subgroups defined by the 5 factors (i.e., sex, age, race, history of diabetes, and type of P2Y12 inhibitor). We aimed to assess the efficacy of DAT vs TAT in these patient subgroups.Methods:We searched PubMed and relevant websites to include related randomized controlled trials (RCTs). Two endpoints of interest were clinically significant bleeding and major adverse cardiac events (MACE). Meta-analysis was performed stratified by 5 factors of interest (i.e., sex, age, race, history of diabetes, and type of P2Y12 inhibitor) to obtain pooled hazard ratio (HR) and 95% confidence interval (CI). Meta-regression analysis was conducted to evaluate subgroup effects. We detected publication bias by Egger test and funnel plots.Results:We included 4 RCTs for meta-analysis. DAT vs TAT significantly reduced the risk of clinically significant bleeding (HR 0.56, 95% CI 0.50–0.63). This effect of DAT was observed in most subgroups of interest (HR ranged from 0.54 to 0.69), and was consistent across various subgroups defined by each of the 5 factors of interest (P_subgroup ranged from 0.290 to 0.794). DAT vs TAT led to the similar risk of MACE (HR 0.98, 95% CI 0.89–1.08). This effect of DAT was observed in all subgroups of interest (all 95% CIs of HRs were across 1.0), and was consistent across various subgroups defined by each of the 5 factors of interest (P_subgroup ranged from 0.308 to 0.828). Publication bias was found only in one subgroup.Conclusions:Compared with TAT, DAT significantly reduces the risk of clinically significant bleeding and leads to the similar risk of MACE in patients with atrial fibrillation following PCI, irrespective of sex, age, race, history of diabetes, and type of P2Y12 inhibitor used at baseline.     

Impact of triple antithrombotic therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention in real-world practice

Objective The optimal antithrombotic regimen for patients on oral anticoagulation (OAC) after acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI) remains debated. This study sought to evaluate the efficacy and safety of OAC plus clopidogrel with or without aspirin in a real-world setting. Methods We retrospectively analyzed data from an international, multi-center registry between 2003 and 2014 (n = 15,401). Patients with ACS and receiving OAC after PCI were screened. The composite primary endpoint was 1-year all-cause death, re-infarction, or severe bleeding. Results The final analysis enrolled 642 patients including 62 patients (9.7%) with OAC and clopidogrel (dual therapy), and 580 patients (90.3%) with the combination of aspirin, OAC and clopidogrel (triple therapy). Patients on triple therapy were more often female and were more likely to have comorbidities. There was no significant difference regarding the primary end point between dual therapy with triple therapy patients [17.74% vs. 17.24%; unadjusted hazard ratio (HR): 1.035; 95% confidence interval (CI): 0.556–1.929; adjusted HR: 1.026; 95% CI: 0.544–1.937]. However, the re-infarction rate was significantly higher in dual therapy than triple therapy patients (14.52% vs. 5.34%; unadjusted HR: 2.807; 95% CI: 1.329–5.928; adjusted HR: 2.333; 95% CI: 1.078–5.047). In addition, there was no difference between two regimes in all-cause death and severe bleeding. Conclusions In real-life patients with ACS following PCI and with an indication of OAC, triple therapy was not associated with an increased rate of adverse outcomes compared to dual therapy. Moreover, it decreased risk of re-infarction and did not increase risk of severe bleeding.     

Looking into the next decade of antithrombotic therapy for patients with atrial fibrillation and percutaneous coronary intervention

Journal of Thrombosis and Thrombolysis - Patients with atrial fibrillation who undergo percutaneous coronary intervention are at increased risk for both coronary and cerebral thrombotic events. As...     

Argatroban anticoagulation during percutaneous coronary intervention in patients with heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated syndrome associated with thrombosis. Alternative anticoagulation to heparin is needed for HIT patients during percutaneous coronary intervention (PCI). We evaluated argatroban, a direct thrombin inhibitor, for anticoagulation in this setting. Ninety-one HIT patients underwent 112 PCIs while on intravenous argatroban (25 microg/kg/min [350 microg/kg initial bolus], adjusted to achieve an activated clotting time of 300-450 sec). Primary efficacy endpoints were subjective assessments of the satisfactory outcome of the procedure and adequate anticoagulation during PCI. Among patients undergoing initial PCIs with argatroban (n = 91), 94.5% had a satisfactory outcome of the procedure and 97.8% achieved adequate anticoagulation. Death (zero patients), myocardial infarction (four patients), or revascularization (four patients) at 24 hr after PCI occurred in seven (7.7%) patients overall. One patient (1.1%) experienced periprocedural major bleeding. For patients who had subsequent hospitalizations (mean separation of 150 days) for repeat PCI using argatroban anticoagulation (n = 21), there were no unsatisfactory outcomes. Overall, outcomes were comparable with those historically reported for heparin. Argatroban therefore is a reasonable anticoagulant option in this setting, where current options are limited.     

早期他汀序贯治疗在行经皮冠状动脉介入治疗冠心病患者中的临床应用

目的评价冠心病行经皮冠状动脉介入治疗（PCI）患者中早期应用阿托伐他汀序贯治疗方法的安全性和有效性。方法170例冠心病患者随机分为序贯治疗组和常规治疗组,每组85例。比较两组基线资料,随访观察治疗前后1周、1个月、3个月、6个月的总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、肝功能、肾功能、肌酸激酶（CK）、超敏C反应蛋白（hsCRP）等生化指标的变化以及不良事件和不良反应的发生情况。结果两组治疗后LDL-C和TC的水平较治疗前均有显著下降（P〈0．05）。两组1周时LDL-C和TC的下降幅度差异有统计学意义（LDL-C：31．2％vs12．5％;TC：29．2％vs13．1％;P〈0．05）,1个月时在原有基础上进一步降低,两组差异有统计学意义（LDL-C：43．0％vs17．6％;TC：41．3％vs22．3％：P〈0．05）。3个月和6个月时,两组间LDL-C和TC变化无统计学差异（P〉0．05）。序贯治疗组1周、1个月、3个月时LDL-C的达标率明显高于常规治疗组（1周：48．2％ vs 25．9％;1个月：77．6％vs60．0％;3个月：81．2％vs68．2％;P〈0．05）。与治疗前相比,两组均可显著降低hs-CRP的水平,序贯治疗组1周和1个月时hs-CRP降低幅度明显大于常规治疗组f序贯治疗组治疗前（8．17±5．69）mg／L,1周时（4．23±2．43）mg／L,1个月时（1．96±0．77）mg／L;常规治疗组治疗前（7．75±4．31）mg／L,1周时（4．87±2．70）mg／L,1个月时（3．21±1．27）mg／L;P＜0．05]。序贯治疗组6个月内主要心血管事件发生率明显低于常规治疗组（5．9％vs15．3％,P〈0．05）,序贯治疗组比常规治疗组风险进一步降低了9．4％。序贯治疗组不良反应轻微,两组不良反应发生率差异无统计学意义（P〉0．05）。结论他汀序贯治疗的疗效和安全性良好,可以明显改善冠心病PCI术患者的临床预后。     

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...     

Prospective randomized study of argatroban versus heparin anticoagulation therapy after percutaneous coronary intervention for acute myocardial infarction

OBJECTIVES: Argatroban, a selective thrombin inhibitor, is expected to decrease acute coronary re-occlusion and restenosis via direct suppression of thrombin generation after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction. This study evaluated the effect of argatroban compared with heparin as an adjunctive anticoagulation therapy after PCI in patients with acute myocardial infarction. METHODS: Fifty-four consecutive patients with acute myocardial infarction underwent PCI within 6 hr from the onset and were randomly allocated to receive argatroban (argatroban group: n = 27) or heparin (heparin group: n = 27) after PCI. Each drug was administered intravenously for 72 hr. Coronary angiography was repeated at 1 and 6 months after the onset of acute myocardial infarction. In-hospital cardiac events, bleeding complications, and long-term outcome were surveyed. RESULTS: Baseline clinical and angiographic variables were similar in the two groups. Acute coronary re-occlusion and major hemorrhagic complications did not occur in either group. Minor bleeding complications, such as hematoma of the puncture sites, occurred significantly less frequently in the argatroban group than in the heparin group (4% vs 30%, p < 0.05). After 6 months, there were no significant differences in restenosis rate and target vessel recanalization rate between the two groups. Subgroup analyses revealed no significant differences in restenosis rate between patients treated with only balloon angioplasty and stent implantation. CONCLUSIONS: Argatroban provides similar prevention of acute thrombotic events and restenosis compared with heparin. However, argatroban might reduce bleeding complications in patients with acute myocardial infarction after PCI.     

Heparin or enoxaparin anticoagulation for primary percutaneous coronary intervention

Objectives : The aim of this study was to compare efficacy and safety outcomes among patients receiving enoxaparin or unfractionated heparin (UFH) while undergoing percutaneous coronary intervention (PCI) for ST‐segment elevation myocardial infarction (STEMI). Background : Primary PCI (pPCI) for ST elevation has traditionally been supported by UFH. The low molecular weight heparin enoxaparin may provide better outcomes when used for pPCI. Methods : Consecutive eligible patients (580) undergoing pPCI enrolled in the prospective electronic Pitié‐Salpêtrière registry of ischemic coronary syndromes (e‐PARIS) registry were grouped according to whether they received UFH or enoxaparin as the sole anticoagulant. Logistic regression modeling, propensity‐weighted adjustment, and sensitivity analyses were used to evaluate efficacy and safety endpoints for enoxaparin vs. UFH. Results : Enoxaparin was administered to 346 patients and UFH to 234 without ACT or anti‐Xa guided dose adjustment. PCI was performed through the radial artery in 90%, with frequent (75%) use of GPIIb/IIIa antagonists. Patients receiving enoxaparin were more likely to be therapeutically anticoagulated during the procedure (68% vs. 50%, P < 0.0001) and were less likely to experience death or recurrent myocardial infarction (MI) in hospital (adjusted OR 0.28 95% CI (0.12–0.68) or by 30 days (adjusted OR 0.35 95% CI 0.16–0.81). All cause mortality was also reduced in hospital (adjusted OR 0.32, 95% CI (0.12–0.85) and to 30 days (adjusted OR 0.40 95% CI 0.17–0.99). Other ischemic endpoints were similarly reduced with enoxaparin. Thrombolysis in myocardial infarction (TIMI) major bleeding events were numerically fewer among patients receiving enoxaparin (1.2% vs. 2.6%, P = 0.2). Conclusions : In patients with STEMI presenting for PCI, enoxaparin was associated with a reduction in all ischemic complications, more frequent therapeutic anticoagulation, and no increase in major bleeding when compared against unfractionated heparin. © 2010 Wiley‐Liss, Inc.