Clinical use of clopidogrel in acute coronary syndrome

Several therapeutic approaches have been developed to improve the outcome among patients with acute coronary syndrome (ACS). However, treatment with antithrombotic therapies such as oral glycoprotein IIb/IIIa inhibitors has been limited by the lack of efficacy and excess bleeding complications. As the publication of the landmark study Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE), the clinical benefit of early and intermediate-term use of combined antiplatelet agents--clopidogrel plus aspirin--in non-ST-segment elevation myocardial infarction (NSTEMI) patients became evident. Pretreatment and intermediate-term therapy with clopidogrel in NSTEMI ACS patients undergoing percutaneous coronary intervention (PCI) was further supported by the PCI-CURE trial. Recently, the results of two major trials Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction 28, Clopidogrel and Metoprolol in Myocardial Infarction Trial established the pivotal role of clopidogrel in the other spectrum of ACS-STEMI. Coupled with the results from previous multicentre trials, these two studies provide a guide for the early and long-term use of clopidogrel in the whole spectrum of ACS. A review summarising the results of the recent clinical trials and a discussion on its implications for the clinical management of ACS is presented.     

Unmet needs in oral antiplatelet therapy with ADP receptor blocking agents

Antiplatelet agents like aspirin and clopidogrel are treatment cornerstones for acute coronary syndromes (ACS). Drawbacks of dual therapy with these agents include slow onset and offset of effect and wide response variability. Clopidogrel may provide little benefit if administered too close to percutaneous coronary intervention (PCI) and increase major bleeding risk if given too close to coronary artery bypass grafting (CABG) or other surgery. It may not provide sufficient antiplatelet coverage prior to CABG if stopped too long before intervention and leave patients without antiplatelet coverage due to hyporesponsiveness. Prasugrel has made steps towards addressing these limitations by exhibiting more efficient metabolism, more rapid onset of effect, and greater and more consistent platelet inhibition than clopidogrel. The TRITON-TIMI38 trial in ACS patients undergoing PCI showed prasugrel produced greater ischemic event protection than clopidogrel but significantly increased major bleeding risk. AZD6140, the first reversible oral P2Y₁₂ inhibitor, provides more rapid onset of effect and greater and more consistent platelet inhibition than clopidogrel. In DISPERSE2, a phase II trial in ACS patients, AZD6140 did not increase bleeding risk, reduced bleeding risk among CABG patients, and produced numerical reductions in myocardial infarction risk. AZD6140 is being compared with clopidogrel in PLATO, a phase III trial in approximately 18000 ACS patients.     

Long-term combination therapy with aspirin and clopidogrel

The possible additive antiplatelet effects of aspirin and clopidogrel have been explored in the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) and Management of Atherothrombosis with Clopidogrel in High Risk Patients (MATCH) studies. To assess the overall absolute beneficial and/or harmful impact of aspirin and clopidogrel combination therapy compared with monotherapy with either drug, we analyzed the results from both trials in terms of number needed to treat per year. Treating between 35 and 204 at-risk patients for 1 year with combination therapy appeared to prevent 1 patient from experiencing an adverse primary cardiovascular outcome; whereas, about 1 in 63 such patients appeared liable to major bleeding during that period. We determined that the evidence to date indicates no overall advantage for combination therapy with anti-platelet drugs in preference to monotherapy.     

三联抗血小板药物对非ST段抬高性急性冠脉综合征患者血清炎症因子及内皮功能的影响

目的探讨短期三联抗血小板药物对非ST段抬高性急性冠脉综合征(ACS)患者血清炎症因子和血管内皮功能的影响,为三联抗血小板药物治疗非ST段抬高性ACS提供进一步的临床依据。方法急性非ST段抬高性ACS患者82例,随机分为三联抗血小板药物治疗组(治疗组)和二联抗血小板治疗组(对照组);观察组患者给予阿司匹林、氯吡格雷、替罗非班三联抗血小板药物;对照组患者给予阿司匹林,氯吡格雷二联抗血小板药物。观察治疗48 h后患者血清炎症因子(hs-CRP、IL-6)及反映血管内皮功能的指标(ET-1、NO、PGI2)的水平变化情况。结果三联抗血小板药物较二联抗血小板药物更有效地降低非ST段抬高性ACS患者血清炎症因子及改善血管内皮功能,主要的不良反应为皮下瘀斑、牙龈出血。结论对于非ST段抬高性ACS患者,三联抗血小板药物在短期的抗炎、改善血管功能方面要优于二联抗血小板治疗,值得临床推广应用。     

Antiplatelet therapy for secondary prevention of acute coronary syndrome, transient ischemic attack, and noncardioembolic stroke in an era of cost containment

Physicians are aware of the profound impact of oral antiplatelet therapy for secondary prevention of acute coronary syndrome (ACS), transient ischemic attack, and noncardioembolic stroke. Numerous clinical studies have compared the benefits of aspirin (ASA) alone with those of combination therapy with extended-release dipyridamole or with those of clopidogrel, with or without ASA, for secondary stroke prevention; and of ASA monotherapy compared with ASA plus clopidogrel combination therapy for secondary prevention in various ACS populations. More recently, ASA plus prasugrel has been compared with ASA plus clopidogrel in a high-risk ACS population. However, given the different treatment modalities and methods used in the various trials, it is difficult to make generalizations as to which therapy is most effective with the lowest risk of bleeding. Further complicating physician's decision making are cost considerations, particularly with the newer oral antiplatelet agents, which are considerably more expensive than ASA. This review provides a brief overview of the clinical data on each of the currently marketed oral antiplatelet agents and the available data on cost-effectiveness for the secondary prevention of ACS, transient ischemic attack, and noncardioembolic stroke.     

Antiplatelet options for secondary prevention in acute coronary syndromes

Current guidelines recommend dual antiplatelet therapy, a combination of aspirin and a P2Y(12) inhibitor, for 6?12 months after percutaneous coronary intervention with drug-eluting stent implantation in all patients and for 1 year in all patients after an acute coronary syndrome (ACS), irrespective of revascularization strategy. Clopidogrel has a pharmacokinetic and pharmacodynamic profile that results in a delayed and/or subtherapeutic antiplatelet effect, and wide variability in antiplatelet response. New P2Y(12) inhibitors, such as prasugrel and ticagrelor, have favorable pharmacodynamics and clinical efficacy over clopidogrel and offer an alternative antiplatelet treatment strategy in specific patients. Prasugrel has more potent, rapid, and consistent effects on inhibiting ADP-induced platelet aggregation than clopidogrel. Ticagrelor also appears to have more rapid and consistent antiplatelet effects than clopidogrel. The higher levels of antiplatelet inhibition provided by prasugrel and ticagrelor compared with standard-dose clopidogrel result in improved ischemic outcomes in patients with ACS. Despite an increase in bleeding risk, prasugrel and ticagrelor appear to have a better net clinical benefit, especially in higher-risk patients with ACS.     

Antiplatelet options for secondary prevention in acute coronary syndromes

Current guidelines recommend dual antiplatelet therapy, a combination of aspirin and a P2Y₁₂ inhibitor, for 6–12 months after percutaneous coronary intervention with drug-eluting stent implantation in all patients and for 1 year in all patients after an acute coronary syndrome (ACS), irrespective of revascularization strategy. Clopidogrel has a pharmacokinetic and pharmacodynamic profile that results in a delayed and/or subtherapeutic antiplatelet effect, and wide variability in antiplatelet response. New P2Y₁₂ inhibitors, such as prasugrel and ticagrelor, have favorable pharmacodynamics and clinical efficacy over clopidogrel and offer an alternative antiplatelet treatment strategy in specific patients. Prasugrel has more potent, rapid, and consistent effects on inhibiting ADP-induced platelet aggregation than clopidogrel. Ticagrelor also appears to have more rapid and consistent antiplatelet effects than clopidogrel. The higher levels of antiplatelet inhibition provided by prasugrel and ticagrelor compared with standard-dose clopidogrel result in improved ischemic outcomes in patients with ACS. Despite an increase in bleeding risk, prasugrel and ticagrelor appear to have a better net clinical benefit, especially in higher-risk patients with ACS.     

Oral antiplatelet agents in ACS: from pharmacology to clinical differences

Antiplatelet agents play an essential role in the treatment of acute coronary syndrome (ACS). Numerous clinical trials have established the value of antiplatelet therapies for ACS. Aspirin (ASA), thienopyridines and GP IIb/IIIa antagonists comprise the major classes of antiplatelet therapies demonstrated to be of benefit in the treatment of ACS. Thienopyridines are a class of drugs that function via inhibition of the adenosine diphosphate (ADP) P2Y12 platelet receptors. Currently, clopidogrel, a second generation thienopyridine, is the main drug of choice and the combination of aspirin and clopidogrel is administered orally for the treatment of ACS. Recently, a third generation of thienopyridines has been introduced represented by prasugrel that has demonstrated promising results in ACS patients treated with percutaneous coronary intervention (PCI). A number of nonthienopyridine oral antiplatelet drugs are under development, and one of them, ticagrelor has already been tested in a major phase III clinical trial, PLATO, with the inclusion of a broad spectrum of patients with ACS. The present review aims to discuss the present knowledge about the safety and efficacy of oral antiplatelet treatment of patients with ACS.     

Antiplatelet therapy in acute coronary syndromes: the emergency physician's perspective

The platelet plays a central role in the pathogenesis of coronary thrombosis after atherosclerotic plaque rupture, and its active inhibition forms a cornerstone of the management of acute coronary syndromes (ACS). Early treatment with clopidogrel in addition to aspirin is more effective than aspirin alone in reducing recurrent ischemic events in patients presenting with ACS, and is a useful adjunct to percutaneous coronary intervention, especially with stenting. There is a potential for increased bleeding complications in patients on clopidogrel therapy who subsequently undergo urgent coronary artery bypass graft surgery. Consequently, many emergency physicians withhold clopidogrel treatment until it is clear that urgent coronary artery bypass graft surgery will not be required. The potential untoward effects seem to be minimized by withholding antiplatelet therapy 3-5 days before surgery. Intravenous glycoprotein (GP) IIb/IIIa receptors inhibitors are also particularly useful in patients who undergo percutaneous coronary intervention, and may have some utility in the medical management of patients with high-risk non-ST-segment elevation ACS, starting in the emergency department. For patients presenting to the emergency department with ACS, the benefits and risks of initiating clopidogrel or GP IIb/IIIa inhibitor therapy need to be considered on an individual basis.     

Anticoagulant and/or antiplatelet treatment in patients with atrial fibrillation after percutaneous coronary intervention. A single-center experience

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia sustained and frequently occurs in patients with coronary heart disease. Thus, a large number of patients requiring percutaneous coronary intervention (PCI) also suffer from AF. An anticoagulant regimen has not been standardized for patients with AF after coronary stent implantation. PATIENTS AND METHODS: The authors investigated data from 159 patients with AF who underwent PCI in their department. Baseline variables and incidence of a combined endpoint (stroke, myocardial infarction, cardiovascular death, severe bleeding) were compared in patients receiving clopidogrel and acetylsalicylic acid (ASA; group 1) versus patients receiving the combination of clopidogrel and ASA with low-molecular-weight heparin (LMWH; group 2) versus patients receiving the combination of clopidogrel and ASA with oral anticoagulation (OAC; group 3) at discharge. RESULTS: Patients discharged with triple therapy including OAC seemed to be at higher risk: patients in group 3 had decreased left ventricular ejection fraction and increased inflammatory state as measured by plasma fibrinogen and C-reactive protein. Moreover, previous OAC treatment and strokes were found more often in this subgroup of patients. In a median follow-up of 1.4 years, two severe bleeding events (both in group 1), four myocardial infarctions (all in group 1), 13 strokes (nine in group 1, four in group 2), and nine cardiovascular deaths (three in group 1, five in group 2, one in group 3) occurred. CONCLUSION: In this analysis, no treatment regimen seemed to be clearly superior. It underlines the importance of prospective, randomized trials to investigate the optimal antithrombotic/antiplatelet treatment for patients with AF after PCI.     

Prasugrel hydrochloride for the treatment of acute coronary syndrome patients

Introduction: Dual antiplatelet therapy (DAPT) with aspirin combined with either a thienopyridine (clopidogrel or prasugrel) or acyclopentyl-triazolo-pyrimidine (ticagrelor) plays a vital role in the management of acute coronary syndrome (ACS) especially in those undergoing percutaneous coronary intervention (PCI) but even those being managed medically. Observational studies and some formal studies have shown patients on the standard dual antiplatelet regimen (clopidogrel and aspirin) continue to have further ischemic events and can suffer stent thrombosis. It has been demonstrated that clopidogrel is associated with a delayed onset of action with a considerable inter-individual variation to treatment thus making it difficult to achieve an optimal level of platelet inhibition.

Areas covered: This article will review the current evidence that is available regarding the effectiveness and safety of prasugrel in ACS patients undergoing percutaneous coronary intervention (PCI).

Expert commentary: Prasugrel is an oral third-generation inhibitor of platelet activation and aggregation. Laboratory studies and early phase clinical trials show prasugrel has a faster onset of action, is more potent and has reduced inter-patient response variability compared to clopidogrel. The published studies so far demonstrated that prasugrel when compared to clopidogrel also shows a higher degree of effectiveness in the prevention of platelet-initiated thrombotic events in patients with ACS undergoing PCI, however these benefits are offset somewhat by an increased bleeding risk.     

经皮冠状动脉介入治疗早期增加氯吡格雷剂量对主要不良心血管事件的影响

目的 观察高危急性冠状动脉综合征(ACS)患者(包括不稳定性心绞痛、急性ST段抬高型心肌梗死和急性非ST段抬高型心肌梗死)经皮冠状动脉介入治疗(PCI)早期不同剂量氯吡格雷对主要不良心血管事件(MACE)的影响.方法 选择2008年1月至2011年6月因ACS行PCI术的患者共160例,所有患者按入院先后随机分为两组,一组为治疗组(80例),患者入院后阿司匹林300 mg顿服,后以100 mg qd,长期口服;氯吡格雷300 mg顿服,后以150 mg qd口服2周,2周后给予氯吡格雷75 mg qd至少1年;另一组为对照组(80例),患者入院后阿司匹林300 mg顿服,后以100 mg qd,长期口服,氯吡格雷75 mgqd至少1年.两组其余药物治疗均相同.分别于PCI术后1个月、6个月时观察MACE的影响.结果 两组患者临床基线特征基本一致,病变血管分布情况差异无统计学意义.两组患者PCI术后24 h、3d均未发生心脏不良事件,于术后1个月时,两组MACE的发生情况,治疗组低于对照组(6.2%vs.7.5%),但差异不具有统计学意义(P>0.05).而于术后6个月时,治疗组MACE的发生明显低于对照组(10.0%vs.17.5%),差异有统计学意义(P<0.05).结论 ACS患者在一般治疗的基础上,介入治疗时早期增加氯吡格雷的剂量可降低PCI术后MACE的发生率.     

国产替罗非班对老年急性冠脉综合征介入治疗患者近远期预后的影响

目的 评价国产替罗非班对老年急性冠脉综合征(ACS)接受经皮冠状动脉介入治疗(PCI)患者近期和远期预后的影响.方法 选择接受PCI治疗的325例年龄≥60岁的ACS患者,根据是否使用替罗非班分为替罗非班组(210例)和对照组(115例).两组患者术中均植入药物洗脱支架,口服阿司匹林+氯吡格雷;替罗非班组在此基础上加用替罗非班.比较两组基线资料,支架植入即刻心肌梗死溶栓血流(TIMI)3级的比例,支架内血栓发生率,轻微出血、大出血和血小板减少发生率,术后30 d和12个月的病死率、心肌梗死(心梗)和靶血管血运重建(TVR)的发生率.结果 替罗非班组PCI后即刻TIMI血流3级的比例高于对照组(99.05％比94.78％,P＜0.05),支架内血栓发生率明显低于对照组(0.47％比2.61％,P＜0.05);替罗非班组术后30 d和12个月病死率、心梗和TVR发生率明显低于对照组(30 d:0、0.47％、0.47％比2.61％、3.48％、2.61％;12个月:0、0.47％、0.47％比2.61％、5.22％、5.22％,P＜0.05或P＜0.01);替罗非班组轻微出血发生率高于对照组,但差异无统计学意义(7.14％比4.35％,P＞0.05);两组均无大出血病例;替罗非班组血小板减少发生率较对照组有所升高(0.95％比0,P＞0.05).结论 国产替罗非班可明显改善老年ACS患者PCI术后即刻TIMI血流状况,有效降低支架内血栓发生率,减少术后30 d和12个月的病死率及心梗和TVR发生率,且不增加大出血和血小板减少的发生,从而改善患者的近期和远期预后.     

Anticoagulation in acute coronary syndrome. An update

The acute coronary syndrome (ACS) is one of the most frequent diagnoses in cardiology. The therapeutic corner-stones of ACS are PCI (percutaneous coronary intervention) and inhibition of blood coagulation. Current antiplatelet therapy consists of aspirin in combination with clopidogrel and glycoprotein IIb/IIIa blockade if needed. Prasugel is a new antiplatelet agent that is in the process of being approved for routine clinical use. In terms of antithrombotic therapy latest developments focus on drugs with anti-factor Xa activity, such as fondaparinux, or direct anti-thrombin activity, such as bivalirudin. This review discusses latest developments in the field of anti-platelet and anti-thrombotic therapy for ACS.     

替格瑞洛治疗氯吡格雷低反应患者的有效性及安全性分析

目的 观察替格瑞洛对氯吡格雷低反应急性冠状动脉综合征(acute coronary syndromes,ACS)患者治疗的有效性及安全性。方法 选择2013年1月至2014年6月应用氯吡格雷75 mg/d治疗的ACS经皮冠状动脉介入治疗(PCI)术后患者493例,用血栓弹力图测定血小板聚集率,根据血小板聚集率筛选出氯吡格雷低反应患者173例,采用数字随机法分为氯吡格雷组(n=87)和替格瑞洛组(n=86)。氯吡格雷组继续服用氯吡格雷(75 mg/d),替格瑞洛组将氯吡格雷替换为替格瑞洛(90 mg,2次/d)。主要终点事件为治疗3天、7天、30天二磷酸腺苷(ADP)诱导的血小板聚集率变化情况,次要终点事件为主要不良心脑血管事件(MACCE)及出血的发生率。结果 替格瑞洛组3天、7天、30天血小板聚集率分别为(56.7±12.5)%、(54.1±12.3)%、(53.2±15.3)%显著低于氯吡格雷组(87.7±14.3)%、(85.4±12.7)、(84.9±10.7)%,差异有统计学意义(P<0.01)。对所有患者随访12个月,替格瑞洛组MACCE及出血的发生率显著低于氯吡格雷组(P<0.05)。而两组出血发生率差异无统计学意义(P＞0.05)。结论 对于经皮冠状动脉介入治疗的氯吡格雷低反应患者接受替格瑞洛治疗后能获得理想的抗血小板效果,且替格瑞洛是有效、安全可信赖的药物。     

Glycoprotein IIb/IIIa receptor inhibitors in percutaneous coronary intervention and acute coronary syndrome

OBJECTIVE: To review the contemporary role of the glycoprotein (GYP) IIb/IIIa receptor inhibitors abciximab, eptifibatide, and tirofiban in patients undergoing percutaneous coronary intervention (PCI) and those with an acute coronary syndrome (ACS), and to provide an algorithm based on currently available evidence for specific agents. DATA SOURCES: Primary articles were identified by a MEDLINE search (1966-January 2003); references cited in these articles provided additional resources. STUDY SELECTION AND DATA EXTRACTION: All of the articles identified from data sources were considered for relevant information; this article primarily addresses large, controlled or comparative studies, and meta-analyses. DATA SYNTHESIS: The role of GYP IIb/IIIa inhibitors in patients undergoing PCI and those with ACS has progressed markedly. To date, abciximab has the most robust data in patients undergoing PCI, particularly high-risk individuals. In PCI patients with lower risk (e.g., elective stenting), eptifibatide is a reasonable first-line option. Data do not support tirofiban for routine use in patients undergoing PCI. For individuals with signs and symptoms of ACS, specifically unstable angina or non-ST-segment elevation myocardial infarction (MI), eptifibatide or tirofiban is recommended in high-risk patients when a conservative approach is used (PCI is not planned). Abciximab is not recommended in this situation. In patients with ST-segment elevation MI (STEMI), abciximab is the only GYP IIb/IIIa inhibitor evaluated in large, well-designed investigations. For medical management in combination with a fibrinolytic agent, the role of abciximab remains unclear. For patients undergoing primary PCI for the management of STEMI, the available evidence supports the use of abciximab, albeit further investigation is warranted. CONCLUSIONS: The role of GYP IIb/IIIa inhibitors in clinical cardiology continues to evolve. Choice of the agent depends on situation of use, patient-specific characteristics and risk stratification, and, in the case of ACS, chosen management strategy (medical management or intervention).     

Acute coronary syndrome: peri-interventional antithrombotic therapy

In patients with acute coronary syndrome (ACS), the periinterventional antithrombotic treatment has become increasingly important for the choice of reperfusion strategy and as an adjunct pharmacological treatment prior, during and after percutaneous coronary interventions (PCI). In NSTE-ACS and early invasive strategy (<48 h), treatment with ASA, clopidogrel and heparin - unfractionated heparin (UFH) preferred - should be initiated as soon as possible. Direct thrombin inhibitors are an alternative to heparin, particularly in the setting of increased risk of bleeding and heparin-induced thrombocytopenia. In highrisk patients, an so-called upstream therapy with glycoprotein IIb/IIIa inhibitors (tirofiban, eptifibatide) is recommended as an adjunct to PCI. In STEMI, primary PCI is the reperfusion therapy of choice and should be supported by early adjunct treatment with ASA, clopidogrel, UFH and glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide). "Facilitated" PCI with thrombolytics is not recommended because of increased mortality and complication rates.     

Acute Coronary Syndromes: Diagnosis and Management, Part I

The term acute coronary syndrome (ACS) refers to any group of clinical symptoms compatible with acute myocardial ischemia and includes unstable angina (UA), non—ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI). These high-risk manifestations of coronary atherosclerosis are important causes of the use of emergency medical care and hospitalization in the United States. A quick but thorough assessment of the patient''s history and findings on physical examination, electrocardiography, radiologic studies, and cardiac biomarker tests permit accurate diagnosis and aid in early risk stratification, which is essential for guiding treatment. High-risk patients with UA/NSTEMI are often treated with an early invasive strategy involving cardiac catheterization and prompt revascularization of viable myocardium at risk. Clinical outcomes can be optimized by revascularization coupled with aggressive medical therapy that includes anti-ischemic, antiplatelet, anticoagulant, and lipid-lowering drugs. Evidence-based guidelines provide recommendations for the management of ACS; however, therapeutic approaches to the management of ACS continue to evolve at a rapid pace driven by a multitude of large-scale randomized controlled trials. Thus, clinicians are frequently faced with the problem of determining which drug or therapeutic strategy will achieve the best results. This article summarizes the evidence and provides the clinician with the latest information about the pathophysiology, clinical presentation, and risk stratification of ACS and the management of UA/NSTEMI.ACC = American College of Cardiology; ACE = angiotensin-converting enzyme; ACS = acute coronary syndrome; ADP = adenosine diphosphate; AHA = American Heart Association; BNP = B-type natriuretic peptide; CABG = coronary artery bypass grafting; CAD = coronary artery disease; CHF = congestive heart failure; CI = confidence interval; CK-MB = muscle and brain fraction of creatine kinase; CRP = C-reactive protein; CURE = Clopidogrel in Unstable Angina to Prevent Recurrent Events; ECG = electrocardiography; ED = emergency department; GP = glycoprotein; HR = hazard ratio; IV = intravenous; LDL = low-density lipoprotein; LMWH = low—molecular-weight heparin; LV = left ventricular; MI = myocardial infarction; NSTEMI = non—ST-segment elevation MI; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation MI; TIMI = Thrombolysis in Myocardial Infarction; UA = unstable angina; UFH = unfractionated heparinThe term acute coronary syndrome (ACS) refers to any group of clinical symptoms compatible with acute myocardial ischemia and covers the spectrum of clinical conditions ranging from unstable angina (UA) to non—ST-segment elevation myocardial infarction (NSTEMI) to ST-segment elevation myocardial infarction (STEMI). Unstable angina and NSTEMI are closely related conditions: their pathophysiologic origins and clinical presentations are similar, but they differ in severity. A diagnosis of NSTEMI can be made when the ischemia is sufficiently severe to cause myocardial damage that results in the release of a biomarker of myocardial necrosis into the circulation (cardiac-specific troponins T or I, or muscle and brain fraction of creatine kinase [CK-MB]). In contrast, the patient is considered to have experienced UA if no such biomarker can be detected in the bloodstream hours after the initial onset of ischemic chest pain. Unstable angina exhibits 1 or more of 3 principal presentations: (1) rest angina (usually lasting >20 minutes), (2) new-onset (<2 months previously) severe angina, and (3) a crescendo pattern of occurrence (increasing in intensity, duration, frequency, or any combination of these factors). Each year in the United States, approximately 1.36 million hospitalizations are required for ACS (listed either as a primary or a secondary discharge diagnosis), of which 0.81 million are for myocardial infarction (MI) and the remainder are for UA. Roughly two-thirds of patients with MI have NSTEMI; the rest have STEMI.¹     

New P2Y12 blockers

Summary.  A number of new antiplatelet agents currently in development are anticipated to improve clinical outcomes and safety benefits in patients with acute coronary syndrome (ACS). This article reviews the pharmacology and clinical development of three of these agents: prasugrel, cangrelor, and ticagrelor. Prasugrel, a third-generation, oral thienopyridine, has been shown to be superior to clopidogrel, the current gold standard, in preventing ischemic events in patients with ACS undergoing percutaneous coronary intervention (PCI), although the bleeding rate was higher. Cangrelor, a chemical analog of adenosine triphosphate, is a potent direct platelet P2Y₁₂ antagonist. In development as an intravenous agent, cangrelor is currently being evaluated in two phase III studies in patients requiring PCI. Ticagrelor is the first of a new class of orally available antiplatelet agents antagonizing the effects of ADP mediated by P2Y₁₂; it is currently being studied in a phase III trial in patients with ACS.     

Acute coronary syndromes: identifying the appropriate patient for prasugrel

Acute coronary syndrome (ACS) remains the leading cause of morbidity and mortality. More than half of patients presenting with ACS will experience a recurrent ischemic event; thus, preventing recurrent events is essential to reduce morbidity and mortality associated with ACS. While dual antiplatelet therapy with aspirin and clopidogrel has been the foundation of management for patients presenting with ACS, clopidogrel is limited by delayed antiplatelet effect and a variable patient response. Prasugrel is more potent, has a more rapid and consistent antiplatelet effect, and has been associated with improved outcomes compared with clopidogrel in select patients with ACS. Although prasugrel reduces the risk of recurrent cardiovascular events, it also increases the risk of major bleeding. Careful patient selection will improve the likelihood that patients treated with prasugrel will experience the benefit of this antiplatelet agent with the lowest possible risk of an adverse event. This article reviews the data supporting the use of prasugrel in ACS with an emphasis on characteristics that will help identify the most appropriate patient for this therapy.