Single antiplatelet therapy after percutaneous coronary intervention in patients allergic to aspirin

Dual antiplatelet therapy including aspirin and a P2Y₁₂ ADP receptor antagonist is given after percutaneous coronary intervention to avoid catastrophic complication of stent thrombosis. Dual antiplatelet therapy is associated with increased bleeding risk and may not be tolerated by many patients. This article presents the patients, which had to be given single antiplatelet therapy after percutaneous coronary intervention and discusses the possible factors responsible for the success of single antiplatelet therapy strategy in these patients, in the current era of newer antiplatelet agents and coronary stents.     

Long-term successful percutaneous coronary intervention in factor VII deficiency

Factor VII deficiency (FVIId) is a congenital coagulation disorder with a wide spectrum of bleeding phenotypes. Percutaneous coronary intervention requires full anticoagulation during stent implantation to avoid acute coronary thrombosis and long-term dual antiplatelet therapy. Feasibility of percutaneous coronary intervention in FVIId is not described in literature. We present a successful case of percutaneous coronary intervention in a 55-year-old male with FVIId, discussing briefly the periprocedural handicaps (anticoagulation regimen and hemostasis at arterial puncture site) as the safety of long-term antiplatelet therapy, and future implications for recombinant FVIId administration in a patient with a previous coronary stent.     

Antithrombotic treatment in anticoagulated atrial fibrillation patients undergoing percutaneous coronary intervention

Coronary artery disease coexists in a clinically relevant number of patients with atrial fibrillation and it often requires percutaneous coronary intervention. These patients represent a particular challenge for clinicians in terms of antithrombotic management. They require combined antiplatelet–anticoagulant therapy to reduce the risk of recurrent ischemic cardiac events and stroke; however, this antithrombotic strategy is associated with an increased risk of bleeding complications. In the absence of randomized, controlled clinical trials, the majority of current recommendations rely on the results of cohort studies, meta-analyses, post-hoc analyses and subgroup analyses of large, phase III studies. Based on the available evidence, the present review discusses the optimal antithrombotic strategy for patients receiving chronic anticoagulant therapy due to atrial fibrillation who require antiplatelet treatment after acute coronary syndrome and/or percutaneous coronary intervention, and discusses the issue of dental procedures. The correct planning of therapy significantly reduces the risk of bleeding complications and thromboembolic events.Key messagesIn order to reduce the occurrence of recurrent cardiac ischemic events and stroke, anticoagulated patients with acute coronary syndrome and/or percutaneous coronary intervention require a combination of therapies including anticoagulants and antiplatelet drugs.Using the newest optimal combination of therapeutic strategies reduces the risk of haemorrhagic complications.     

Optimal duration of dual antiplatelet therapy post percutaneous coronary intervention in acute coronary syndrome

Dual antiplatelet therapy (DAPT), with aspirin plus a P2Y12 inhibitor agent, is the cornerstone treatment after percutaneous coronary intervention for acute coronary syndrome. Based on randomized clinical trial using aspirin and clopidogrel, a DAPT duration of 12 months has been recommended after an acute coronary syndrome. Despite the development of more potent antiplatelet agents (i.e. prasugrel and ticagrelor) and the reduction in ischemic recurrences after acute coronary syndrome, 12 months DAPT currently remains the gold standard. However, a significant proportion of patients experience recurrent ischemic events beyond the first 12 months after an acute coronary syndrome. Meanwhile, with more effective antiplatelet agent, bleeding has become a major safety concern on DAPT. Therefore, the ischemic and bleeding risk balance is central considering the duration of DAPT after an acute coronary syndrome. This review aims to report the evidence for an optimization and individualization of DAPT duration after an acute coronary syndrome.     

Duration of dual antiplatelet treatment in the era of next generation drug-eluting stents

Current percutaneous coronary intervention guidelines recommend dual antiplatelets(aspirin 100 mg + clopidogrel 75 mg daily) for at least 12 mo following drugeluting stent(DES) implantation if patients are not at high risk of bleeding.Several reports have tried to shorten the dual antiplatelet therapy to 3-6 mo,especially following next-generation DES implantation,for cost-effectiveness.However,the clinical results are inconsistent and the data regarding next-generation DESs limited.In this report,recently published important pivotal reports regarding the optimal duration of dual antiplatelets following DES implantation are summarized.     

Meta-analysis of randomized controlled trials on effect of cilostazol on restenosis rates and outcomes after percutaneous coronary intervention

Cilostazol is a generic drug with antiplatelet and antiproliferative effects. It is unclear whether adding cilostazol to standard dual antiplatelet therapy (aspirin and clopidogrel) after percutaneous coronary intervention reduces restenosis and improves the outcomes. We, therefore, conducted a systematic review and meta-analysis. We systematically searched the Cochrane Library, EMBASE, and MEDLINE databases for randomized controlled trials comparing dual antiplatelet therapy with and without cilostazol after percutaneous coronary intervention. The data were pooled using random-effects models and stratified into short-term (1-month), midterm (1- to 12-month), and long-term (≥12-month) follow-up durations. Twelve randomized controlled trials involving 5,655 patients met our inclusion criteria. The addition of cilostazol to dual antiplatelet therapy was not associated with a significant change in target lesion revascularization (TLR) and target vessel revascularization (TVR) at short-term follow-up. However, TLR and TVR were significantly reduced at midterm follow-up (relative risk 0.57, 95% confidence interval 0.39 to 0.84, and relative risk 0.62, 95% confidence interval 0.47 to 0.83, respectively). Data regarding TLR and TVR at long-term follow-up were limited and inconclusive. We did not find a difference in myocardial infarction, mortality, or major bleeding at any follow-up duration. In conclusion, the addition of cilostazol to dual antiplatelet therapy after percutaneous coronary intervention has favorable effects on TLR and TVR at 1 to 12 months, with no differences in adverse outcomes at any follow-up duration.     

Coronary stenting: A matter of revascularization

In the last few decades, the recommended treatment for coronary artery disease has been dramatically improved by percutaneous coronary intervention(PCI) and the use of balloon catheters, bare metal stents(BMSs), and drug-eluting stents(DESs). Catheter balloons were burdened by acute vessel occlusion or target-lesion restenosis. BMSs greatly reduced those problems holding up the vessel structure, but showed high rates of instent re-stenosis, which is characterized by neo-intimal hyperplasia and vessel remodeling leading to a renarrowing of the vessel diameter. This challenge was overtaken by first-generation DESs, which reduced restenosis rates to nearly 5%, but demonstrated delayed arterial healing and risk for late in-stent thrombosis, with inflammatory cells playing a pivotal role. Finally, new-generation DESs, characterized by innovations in design, metal composition, surface polymers, and antiproliferative drugs, finally reduced the risk for stent thrombosis and greatly improved revascularization outcomes. New advances include bioresorbable stents potentially changing the future of revascularization techniques as the concept bases upon the degradation of the stent scaffold to inert particles after its function expired, thus theoretically eliminating risks linked with both stent thrombosis and re-stenosis. Talking about DESs also dictates to consider dual antiplatelet therapy(DAPT), which is a fundamental moment in view of the good outcome duration, but also deals with bleeding complications. The better management of patients undergoing PCI should include the use of DESs and a DAPT finely tailored in consideration of the potentially developing bleeding risk in accordance with the indications from last updated guidelines.     

Risk and management of upper gastrointestinal bleeding associated with prolonged dual-antiplatelet therapy after percutaneous coronary intervention

Prolonged dual-antiplatelet therapy with aspirin and clopidogrel is mandatory after drug-eluting stent implantation because of the potential increased risk of late stent thrombosis. The concern regarding prolonged antiplatelet therapy is the increased risk of bleeding. Gastrointestinal bleeding is the most common site of bleeding and presents a serious threat to patients due to the competing risks of gastrointestinal hemorrhage and stent thrombosis. Currently, there are no guidelines and little evidence on how best to manage these patients who are at high risk of morbidity and mortality from both the bleeding itself and the consequences of achieving optimum hemostasis by interruption of antiplatelet therapy. Managing gastrointestinal bleeding in a patient who has undergone recent percutaneous coronary intervention requires balancing the risk of stent thrombosis against further catastrophic bleeding. Close combined management between gastroenterologist and cardiologist is advocated to optimize patient outcomes.     

三联抗血小板在老年复杂冠状动脉介入患者术后有效性和安全性对照研究

目的评价西洛他唑、氯吡格雷和阿司匹林三联抗血小板药物在老年复杂冠状动脉介入患者植入多枚药物洗脱支架（DES）术后的疗效和安全性。方法2006年3月至2009年9月人选128例冠状动脉B2／C型病变、采用多DES植入的老年（65-75岁）患者。所有入选患者术后随机分为两组：标准化治疗组（对照组,n=67）和三联抗血小板治疗组（试验组,n=61）。3个月后所有患者接受标准化治疗直至术后12个月。观察两组患者临床特征、冠状动脉病变特点以及支架植入特征,平均随访（20．4±5．1）个月主要心血管事件、支架内血栓和出血事件。结果试验组心肌梗死及再次血运重建发生率均显著低于对照组（6．56％vs11．94％,P=0．043;6．56％vs13．43％,P=0．042）。两组全因病死率差异无统计学意义（1．64％vs2．99％,P=0．615）。试验组主要终点事件绝对风险较对照组降低8．07％（P=0．043）。试验组近期、远期支架内血栓事件发生率显著低于对照组（0．00％vs2．99％,P=0．050;1．64％vs4．48％,P=0．048）：两组间出血发生率差异无统计学意义（P〉0．05）。结论三联抗血小板药物可降低复杂冠状动脉介入老年患者术后发生主要不良心血管事件、支架内血栓形成的风险,并且不增加出血事件的发生风险。     

Clopidogrel and risk for acute coronary events

Clopidogrel bisulfate is a potent adenosine diphosphate receptor blocker that irreversibly inhibits platelet aggregation by preventing the activation of the glycoprotein IIb/IIIa pathway. This helps to prevent thrombus formation and resultant ischemic or thrombotic complications. Clopidogrel was proven to be superior to aspirin in the treatment of atherothrombotic diseases. Clopidogrel plus aspirin, known as dual antiplatelet therapy, is highly effective in patients with acute coronary syndromes or undergoing percutaneous coronary intervention. There is no apparent benefit of dual antiplatelet therapy in primary prevention. In this article, we review the benefits of clopidogrel as an antiplatelet agent and its role in the management of acute coronary syndromes and following percutaneous coronary intervention.     

Treating patients with acute coronary syndromes with aggressive antiplatelet therapy (from the Global Registry of Acute Coronary Events)

Few data exist on the use of aggressive combination therapy with thienopyridines and glycoprotein IIb/IIIa inhibitors in higher risk patients with an acute coronary syndrome (ACS). The aim of this study was to characterize the combined use of these agents and the associated hospital outcomes in patients with ACS enrolled in the multinational Global Registry of Acute Coronary Events. Data from 8,081 patients with non-ST-segment elevation myocardial infarction or unstable angina were analyzed. Of these patients, 5,070 (62.7%) received aspirin and a thienopyridine, and the remainder received aspirin, a thienopyridine, and a glycoprotein IIb/IIIa blocker. The presence of a non-ST-segment elevation myocardial infarction; a history of diabetes or coronary artery bypass surgery; performance of in-hospital catheterization, percutaneous coronary intervention, or coronary artery bypass grafting; and in-hospital use of heparin were independent predictors of the use of triple antiplatelet therapy with aspirin, thienopyridines, and glycoprotein IIb/IIIa blockers. Increased diastolic blood pressure and increased serum creatinine were associated with a failure to prescribe triple therapy. An increased risk of major bleeding during hospitalization was associated with the use of triple antiplatelet therapy (odds ratio 1.6, 95% confidence interval 1.2 to 2.2). Aggressive antiplatelet therapy was used in approximately 2 of every 5 patients presenting with an ACS. Triple therapy was associated with the performance of catheterization and/or percutaneous coronary intervention, as well as high-risk patient features. Although no differences in hospital death rates were evident in patients receiving triple therapy, this population was at significantly increased risk of major bleeding episodes during hospitalization.     

Comparison of long-term outcome of off-pump coronary artery bypass grafting versus drug-eluting stents in triple-vessel coronary artery disease

After the introduction of drug-eluting stents (DESs), percutaneous coronary intervention with DESs has challenged coronary artery bypass grafting as the gold standard for the treatment of 3-vessel coronary artery disease. The purpose of this study was to compare the long-term clinical results between percutaneous coronary intervention with DESs and off-pump coronary artery bypass grafting (OPCAB) in 3-vessel coronary artery disease. Two hundred ninety propensity-score matched patients with 3-vessel coronary artery disease treated by DESs or OPCAB were included. Mean follow-up duration was 58.8 ± 11.5 months (2 to 73) and follow-up rate was 97.9%. Five-year survival rates were 94.8 ± 2.1% in the DES group and 96.5 ± 1.5% in the OPCAB group (p = 0.658). Five-year rates of freedom from major adverse cardiac and cerebrovascular event were 71.6 ± 4.1% in the DES group and 89.6 ± 2.5% in the OPCAB group (p < 0.001). Freedom from nonfatal myocardial infarction and target vessel revascularization rates were the determining factors between the 2 groups (p = 0.018 and p < 0.001, respectively). The OPCAB group showed better clinical outcomes compared to the DES group in 3-vessel coronary artery disease after 5-year follow-up. Freedom from major adverse cardiac and cerebrovascular event rate was significantly higher in the OPCAB group mainly because of the lower incidence of target vessel revascularization and nonfatal myocardial infarction. Longer follow-up with randomization will clarify our present conclusions.     

Comparison of frequency of major adverse events in patients with atrial fibrillation receiving bare-metal versus drug-eluting stents in their coronary arteries

In patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention with drug-eluting stent (DES) implantation, the available evidence from clinical trial data are inconclusive. We evaluated the safety and efficacy of the use of DESs versus bare-metal stents (BMSs) in a consecutive real-world cohort of patients with AF. Of 8,962 unselected patients with AF seen in our institution from 2000 through 2010, 833 (9%) had undergone percutaneous coronary intervention with stent implantation. BMSs were used for 678 patients (81%) and DESs for 155 (19%). During follow-up (median 688 days, interquartile range 1,114), all bleeding episodes, thromboembolism, and major adverse cardiac events (MACEs; i.e., death, acute myocardial infarction, target lesion revascularization) were recorded. Incidence of MACEs was similar in the 2 groups as was incidence of all-cause mortality. Results remained similar even after adjustment for age and other confounding factors. Factors independently associated with an increased risk of MACEs were older age (hazard ratio 1.024, 95% confidence interval 1.004 to 1.044, p = 0.02), implantation of stent during acute ST-segment elevation myocardial infarction (hazard ratio 1.81, 95% confidence interval 1.10 to 2.99, p = 0.02), and stent diameter (hazard ratio 1.09, 95% confidence interval 1.01 to 1.18, p = 0.03). Implantation of DESs was not significantly associated with a higher risk of major bleeding and we observed a similar ratio of serious events at follow-up after DES compared to BMS implantation. In conclusion, in our cohort, systematic use of DESs does not seem to be justified in most patients with AF because it was not associated with any clear advantage compared to BMSs.     

抗血小板治疗与胃肠道出血新进展

冠心病是一种最常见的心脏病,斑块的不稳定、破裂以及血栓形成是贯穿于冠心病发病过程的主要矛盾,随着药物洗脱支架、经皮冠状动脉介入技术日趋成熟,置入药物洗脱支架后联合应用抗血小板聚集药物可明显减少心脏事件的发生。经抗血小板治疗在减少血栓事件的同时也给患者带来了出血的风险,一旦胃肠道出血则对抗血小板治疗形成了十分严峻的挑战,在临床中充分权衡二者的利弊,合理应用。     

Percutaneous coronary intervention in anticoagulated patients via radial artery access

Objectives: To assess safety and feasibility of using radial artery access for percutaneous coronary intervention (PCI) in patients on oral anticoagulation without interrupting therapy. Background: The radial artery approach for PCI is intuitively attractive for patients receiving chronic oral anticoagulation with vitamin K antagonists (VKAs) but little data exist concerning feasibility or safety of this approach in this population. The main advantage of this strategy would be to avoid bridging therapy with heparin that increases risk of thrombotic and bleeding events. Methods: In this prospective observational study, 50 consecutive patients referred for coronary angiography underwent PCI without interrupting oral anticoagulant therapy. The main outcome measures were bleeding and thrombotic complications. Results: The indications for permanent oral anticoagulation were as follows: atrial fibrillation in 62%, mechanical prosthesis in 24%, and venous thromboembolism in 14%. Seventy‐two percent were elective cases and 28% presented with acute coronary syndromes. PCI was performed with an INR range of 1.4–3.4 with mean of 2.2 ± 0.6. Seventy‐six percent of the patients were on dual antiplatelet therapy before the procedure. No thrombotic events or excess bleeding were observed at 1 month. Only one patient had a minor hemorrhage 8 days after procedure. Conclusions: This series suggests that for patients treated with VKAs, the use of radial artery access is feasible and safe for PCI on dual antiplatelet therapy without interrupting oral anticoagulant treatment. © 2008 Wiley‐Liss, Inc.     

Ticagrelor monotherapy in patients undergoing percutaneous coronary intervention for bifurcation lesions

• Ticagrelor monotherapy after a short course of aspirin is emerging as the predominant aspirin‐free strategy among patients undergoing percutaneous coronary intervention.
• In patients included in the GLOBAL‐LEADERS trial, the treatment effect of the experimental (dual antiplatelet therapy with aspirin and ticagrelor for 1 month followed by ticagrelor monotherapy) versus control strategy remained consistent irrespective of the presence or absence of coronary bifurcation.
• Ticagrelor monotherapy represents a safe and effective antiplatelet strategy for the treatment of patients who undergo percutaneous coronary intervention of bifurcation lesions.

     

Immediate and reversible platelet inhibition after intravenous administration of a peptide glycoprotein IIb/IIIa inhibitor during percutaneous coronary intervention

We studied the pharmacokinetic and pharmacodynamic properties or integrelin, a novel platelet glycoprotein IIb/IIIa receptor inhibitor, in patients undergoing elective percutaneous coronary intervention. Patients were randomized to placebo (n = 19) or to 1 of 4 integrelin dosing regimens (total N = 54) that were studied sequentially. All patients received aspirin and heparin. Patients were followed until discharge for the occurrence of adverse clinical events: death, myocardial infarction, coronary artery bypass surgery, repeat intervention, or recurrent ischemia. Bleeding was the primary safety end point. Frequent blood sampling was performed for adenosine diphosphate-induced platelet aggregations. Simplate bleeding times were performed. Adverse clinical events occurred less often in the integrelin-treated patients, although the overall numbers were too small to make a definitive statement as to clinical efficacy. There was no significant increase in serious bleeding among integrelin-treated patients. The 2 highest inregrelin boluses (180 and 135 gmg/kg) immediately (15 minutes after the bolus) provided >80% inhibition of adenosine diphosphate-induced platelet aggregation in >75% of treated patients. A constant inregrelin infusion of 0.75 μg/kg/min maintained this marked antiplatelet effect, whereas an infusion of 0.50 μg/kg/min allowed gradual recovery of platelet function. Elective coronary intervention was performed safely and with no significant increase in serious bleeding events using inregrelin with aspirin and heparin as an antithrombotic regimen. Integrelin provided rapid, intense, and persistent ex vivo platelet inhibition during coronary intervention. This new antiplatelet agent may be beneficial in reducing platelet-mediated ischemic complications of percutaneous coronary intervention.     

Gastrointestinal bleeding after percutaneous coronary intervention

Percutaneous coronary intervention (PCI) is now performed in a wide range of patients with coronary artery disease. Complications of PCI include in-stent re-stenosis and in-stent thrombosis. According to the recent 2005 guidelines of the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions, dual antiplatelet therapy with low-dose aspirin and thienopyridine derivatives such as ticlopidine and clopidogrel should be used in patients who have undergone PCI. A serious complication of dual antiplatelet therapy is bleeding, most of which arise from the gastrointestinal (GI) tract. In this article we review published studies about GI bleeding in patients who have undergone PCI. The prevalence of GI bleeding in patients who are administered dual antiplatelet therapy following PCI is approximately 2%, and GI bleeding after PCI is associated with increased morbidity, mortality, duration of hospitalization and cost. Advanced age, a history of peptic ulcer disease, co-administration of non-steroidal anti-inflammatory drugs, co-administration of anticoagulants, and physiological stress are considered to be the major risk factors for GI bleeding in patients undergoing antiplatelet therapy following PCI. Recent clinical and experimental studies indicate that administration of low-dose aspirin may also increase the risk of adverse events in the small intestine. Although some prophylactic strategies such as proton-pump inhibitor, H? receptor antagonist and eradication of Helicobacter pylori are proposed, there are few randomized controlled trials assessing the best strategy for the prevention of GI bleeding after PCI. Further extensive studies are required to ascertain the beneficial effect of prophylactic agents for dual antiplatelet therapy following PCI.     

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.     

The efficacy and safety of CYP2C19 genotype-guided antiplatelet therapy compared with conventional antiplatelet therapy in patients with acute coronary syndrome or undergoing percutaneous coronary intervention: A meta-analysis of randomized controlled trials

Abstract

Cytochrome P450 (CYP) 2C19 genotype is closely associated with the metabolism and efficacy of clopidogrel, thereby having an important impact on clinical outcomes of patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). This study aimed to evaluate the efficacy and safety of CYP2C19 genotype-guided antiplatelet therapy in patients with ACS or undergoing PCI. PubMed, EMBASE, the Cochrane Library and clinicaltrials.gov were searched to identify randomized controlled trials (RCTs) comparing CYP2C19 genotype-guided antiplatelet therapy with conventional therapy in patients with ACS or undergoing PCI. Eight RCTs involving 6708 patients were included in this meta-analysis. CYP2C19 genotype-guided antiplatelet therapy was slightly superior to the conventional antiplatelet therapy in reducing the risk of MACE [RR(95%CI): 0.71(0.51–0.98), p = .04]. Meanwhile, the genotype-guided therapy group had significantly lower incidence of myocardial infarction [RR(95%CI): 0.56(0.40–0.78), p < .01], but similar risk of all-cause mortality, cardiovascular mortality, stent thrombosis, urgent revascularization and stroke compared to the conventional therapy group. Incidences of major/minor bleeding and major bleeding were comparable between the two groups. In patients with ACS or undergoing PCI, CYP2C19 genotype-guided antiplatelet therapy displayed benefit over conventional antiplatelet therapy in reducing the risk of MACE and myocardial infarction, without increasing bleeding risk. Further RCTs are needed to provide more evidences for CYP2C19 genotype-guided antiplatelet therapy.