Pharmacokinetics and pharmacodynamics of ticagrelor in the treatment of cardiac ischemia

Introduction: After acute coronary syndromes (ACS), the so-called dual antiplatelet therapy (DAPT), which usually consists of low-dose of aspirin in combination with a thienopyridine (clopidogrel, prasugrel) or with a cyclopentyltriazolopyrimidine (ticagrelor), reduces the risk of ischemic events. Ticagrelor, un particular, is an effective drug as it isn’ a prodrug, doesn’t require metabolic activation and demonstrates a rapid onset and faster offset of action.

Areas covered: This article evaluates the pharmacokinetics, efficacy, safety and tolerability of ticagrelor during DAPT after ACS and its potential use beyond the canonical twelve months after PCI. The review discusses studies comparing: ticagrelor and clopidogrel (DISPERSE, DISPERSE-2, PLATO, RESPOND Trial, ONSET/OFFSET Trials), ticagrelor and placebo (PEGASUS TIMI 54 Trial).

Expert opinion: For ACS patients, the PLATO trial showed that ticagrelor was superior to clopidogrel in the reduction of cardiovascular death, myocardial infarction and stroke. PEGASUS TIMI 54 showed that patients in whom ischemic events and cardiovascular death outweigh the risk of life-threatening bleeding, may benefit from prolonged ticagrelor-based dual antiplatelet therapy, over 12 months. This strategy has been recently approved by the ACC/AHA guidelines. Further studies are needed to evaluate and eventually validate the role of the prolonged DAPT in patients treated with new generation stents.     

Ticagrelor for acute coronary syndrome?

Current guidelines from the National Institute for Clinical Excellence (NICE) recommend antiplatelet therapy comprising aspirin plus either clopidogrel or prasugrel for patients with acute coronary syndrome (ACS). However, such dual therapy increases the likelihood of bleeding compared to that with aspirin alone. Ticagrelor (Brilique - Astra-Zeneca) is a new oral antiplatelet drug recently licensed in the UK (since publication of the NICE guidelines) for use with aspirin in patients with ACS, including those managed medically or undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Here we review the place of ticagrelor in the management of people with ACS, and whether it offers advantages over standard therapy in terms of greater efficacy or lower likelihood of bleeding complications.     

Ticagrelor: Positive,negative and misunderstood properties as a new antiplatelet agent

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Ticagrelor: a review of its use in the management of acute coronary syndromes

Ticagrelor (Brilique?; Brilinta?), a cyclopentyl-triazolo-pyrimidine antiplatelet agent, is the first oral antagonist of the P2Y(12) receptor to offer reversible receptor binding. It is indicated in the EU for the prevention of atherothrombotic events in adults with acute coronary syndromes (ACS) [unstable angina pectoris, ST-segment elevation myocardial infarction [STEMI] or non-STEMI), including those managed medically or with percutaneous coronary intervention or coronary artery bypass grafting (CABG). Ticagrelor provides selective and reversible inhibition of adenosine diphosphate-induced platelet aggregation, with a faster onset and offset of action than that of clopidogrel, and is effective in the treatment of patients with ACS, with or without ST-segment elevation. In the large, randomized, double-blind, multicentre PLATO trial conducted in this patient population, ticagrelor was more effective than clopidogrel in terms of preventing ischaemic events over 12 months, providing a significantly lower risk of the primary composite endpoint of myocardial infarction, stroke or death from vascular causes, and was associated with an overall mortality benefit. The risk of major bleeding with ticagrelor, including bleeds related to CABG, did not differ from that seen with clopidogrel in this study, although ticagrelor was associated with more non-CABG-related major bleeds and fatal intracranial bleeding, albeit the latter bleeding events were rare. Further long-term and comparative efficacy and tolerability data are required to definitively position ticagrelor with respect to other antiplatelet agents, including prasugrel. However, the clinical data currently available indicate that ticagrelor is a promising option for the treatment of patients with ACS and may be of particular use in those at high risk of ischaemic events or unresponsive to clopidogrel.     

Emerging antiplatelet therapy for coronary artery disease and acute coronary syndrome

Antiplatelet therapy is used widely with proven benefit for the prevention of further ischemic cardiac complications in patients with known coronary artery disease (CAD) and a history of acute coronary syndrome (ACS). The limitations of conventional antiplatelet therapy with aspirin, clopidogrel, or prasugrel, as well as the fact that rates of recurrent ischemic events still remain high with use of these agents, underscore the need to investigate alternate agents that may further reduce event rates while limiting bleeding risk. The selection of antiplatelet therapy is further influenced by the following: ticagrelor was approved in July 2011 by the United States Food and Drug Administration (FDA), and clopidogrel is slated to become available as a generic productin 2012. We provide an overview of emerging agents for the treatment of CAD and ACS, including the reversible P2Y(12) antagonists ticagrelor, cangrelor, and elinogrel, and a new class of oral protease-activated receptor-1 (PAR-1) inhibitors, vorapaxar and atopaxar.The recently approved P2Y(12) antagonists prasugrel and ticagrelor demonstrate enhanced ability to prevent adverse cardiac outcomes. However, this comes at a cost of a potential increased risk of bleeding. New adverse effects have also emerged, including dyspnea for all of the reversible P2Y(12) antagonists (ticagrelor, cangrelor, and elinogrel) and ventricular pauses for ticagrelor. In addition, the newer P2Y(12) antagonists have a faster onset and offset. Two of these agents, cangrelor and elinogrel, are available as intravenous formulations, which may provide additional benefits in patients who undergo coronary artery bypass graft (CABG) surgery. Trials with the PAR-1 inhibitors have also shown trends toward reductions in cardiac events, but not without the possibility of increased bleeding. More than ever, as the arsenal of antiplatelet therapy expands, health care providers need to understand the pharmacologic and pharmacodynamic differences between conventional and emerging antiplatelet therapies for patients with ACS and CAD. Health care providers must also carefully assess patient-specific factors such as risk of thrombosis, concomitant disease states, age, drug adherence, and aspirin dose, and plan for those patients who will be undergoing CABG when selecting antiplatelet therapy in order to optimally balance bleeding and thrombosis risk.     

Vorapaxar: a novel protease-activated receptor-1 inhibitor

INTRODUCTION: Platelet activation and reactivity are pivotal for both acute and chronic atherothrombotic event occurrences. AREAS COVERED: Only 20% relative risk (～ 2% absolute risk) reduction associated with newer P2Y(12) receptor blocker therapy such as prasugrel and ticagrelor compared with clopidogrel indicates that dual antiplatelet therapy may be associated with a ceiling effect in attenuating platelet-mediated ischemic event occurrence and that residual ischemic event occurrences are mediated by other pathways that are unblocked by current antiplatelet therapy. Therefore, inhibition of the thrombin-protease-activated receptor (PAR)-1 interaction may provide additional benefits in attenuating ischemic event occurrence in selected patients. There are two major PAR-1 blockers are under investigations - vorapaxar and atopaxar. In preclinical and Phase I - II studies, inhibition of thrombin-mediated platelet activation by a PAR-1 inhibitor, in general, has added to the antithrombotic efficacy of aspirin and clopidogrel without increasing bleeding. However, intracranial hemorrhage in patients with a history of stroke associated with vorapaxar and hepatic toxicity associated with atopaxar are important concerns. EXPERT OPINION: At this time, the specific role of PAR-1 inhibitor in the settings of percutaneous coronary intervention and acute coronary syndrome, both during the acute setting and as a long-term therapeutic agent, is not clear. Although the PAR-1 inhibitors are associated with less bleeding, its effectiveness as an antithrombotic agent and also side effects are major concerns. Future large-scale trials with goals addressing these concerns are needed to define the specific role of PAR-1 receptor inhibitor.     

Efficacy and safety of ticagrelor in patients with acute coronary syndrome: A meta‐analysis of randomized controlled trials

Acute coronary syndrome (ACS) is a dangerous and urgent clinical pattern of coronary artery disease. Aspirin and adenosine diphosphate P2Y₁₂ receptor antagonists are the standard dual anti‐platelet therapy for patients with ACS. Ticagrelor is a new oral antagonist of the adenosine diphosphate P2Y₁₂ receptor. Randomized controlled trials (RCTs) have evaluated the efficacy and safety of ticagrelor compared to clopidogrel or prasugrel in patients with ACS, obtaining conflicting results. Thus, we conducted a meta‐analysis of these RCTs to determine the efficacy and safety of ticagrelor in patients with ACS. Results of the meta‐analysis indicate that ticagrelor decreased the risk of major adverse cardiovascular events (MACE) and all‐cause death, but increased the risk of bleeding events. In Asiatic patients, analysis indicates that ticagrelor did not decrease the risk of MACE and all‐cause death, while increasing the risk of bleeding events. Together, this meta‐analysis suggests that ticagrelor was more effective, but less safe than clopidogrel and prasugrel in patients with ACS. Subgroup analysis indicates that ticagrelor was not more effective, although less safe than clopidogrel in Asiatic patients, thus more evidence is needed to further evaluate the efficacy and safety of ticagrelor in Asiatic patients.     

The safety and efficacy of aspirin and clopidogrel as a combination treatment in patients with coronary heart disease

The use of aspirin and clopidogrel in combination has become part of the standard clinical care of patients with coronary artery disease. The use of this combination provides significant benefits compared with the use of aspirin alone in patients with acute coronary syndromes, and in patients treated with percutaneous coronary intervention with stent placement (both bare metal and drug-eluting stents). Clinical trials have demonstrated significant efficacy of this dual therapy; however, there is the potential for significant bleeding complications from the synergistic antiplatelet effects. In total, it appears that when there is vessel injury (mechanical from perctutaneous coronary intervention or a ruptured plaque), dual antiplatelet therapy with aspirin and clopidogrel results in improved outcomes, albeit with a small but significant inherent risk of increased bleeding.     

Ticagrelor. Acute coronary syndromes: nothing new

Several revascularisation methods are effective in patients with acute coronary syndromes. Standard antithrombotic treatment combines heparin and aspirin during the acute phase, followed by long-term aspirin therapy. The only proven advantage of adding clopidogrel is for patients who undergo angioplasty with stenting. Ticagrelor is an antiplatelet drug belonging to a different chemical class than clopidogrel. Its chemical structure resembles that of adenosine. Ticagrelor has been authorised in the European Union for patients with acute coronary syndromes, in combination with aspirin. Clinical evaluation is mainly based on a double-blind randomised trial comparing ticagrelor + aspirin versus clopidogrel + aspirin in 18 624 patients who underwent angioplasty (64% of patients), coronary artery bypass grafting (10%), or who received medical treatment only. Half of the patients were treated for at least 9 months. After 12 months of treatment, compared to the clopidogrel group, overall mortality appeared to be significantly lower in the ticagrelor group (4.5% versus 5.9%), along with cardiovascular mortality (4.0% versus 5.1%). Symptomatic myocardial infarction was also less frequent (5.8% versus 6.9%), but not stroke (about 1.4% in both groups). Ticagrelor did not statistically significantly reduce overall mortality in patients who had angioplasty with stenting, but stent thrombosis was less frequent than with clopidogrel (2.9% versus 3.8%). In combination with aspirin, ticagrelor provoked more bleeding than clopidogrel, based on the definition used in the trial (16.1% versus 14.6%). In contrast, the rate of major bleeding was similar in the two groups (11.5%), including fatal bleeding (0.3%). The adverse effect profile of ticagrelor resembles that of adenosine in certain respects. For example, dyspnoea was more frequent with ticagrelor than with clopidogrel (13.8% versus 7.8%), as were conduction disorders and ventricular pauses at the beginning of treatment (5.8% versus 3.6%). There were also more cases of hyperuricaemia and elevated creatinine levels with ticagrelor. Ticagrelor and its active metabolite are substrates and inhibitors of cytochrome P450 isoenzymes and P-glycoprotein, creating a risk of multiple pharmacokinetic interactions. Pharmacodynamic interactions are also likely to occur, especially with antithrombotic agents and heart-rate-lowering drugs. In practice, in patients with an acute coronary syndrome treated with angioplasty and stenting, and who are also receiving aspirin, it remains to be shown whether the harm-benefit balance of ticagrelor is clearly better than that of clopidogrel. In other settings, there is no firm evidence that ticagrelor is better than aspirin alone.     

Oral antiplatelet therapy and percutaneous coronary intervention

The benefit of oral antiplatelet therapy following percutaneous coronary intervention (PCI) with intracoronary stent implantation is well established. Combined aspirin with clopidogrel or ticlopidine therapy is superior to aspirin alone in reducing thrombotic events after stent placement. Clopidogrel is the drug of choice, given that its efficacy is comparable to ticlopidine and it has a superior safety profile. Despite dual antiplatelet therapy, patients remain at risk of recurrent vascular events. Optimal timing, duration and dosage of antiplatelet therapy remain controversial. Recent evidence suggests additional benefit with clopidogrel pretreatment, high clopidogrel loading dose and long-term dual antiplatelet therapy post-PCI in high-risk patients.     

新型P2Y12受体抑制剂替格瑞洛临床研究进展

抗血小板药物是急性冠脉综合征（Acute Coronary Syndrome,ACS）治疗的基石,对防治心肌缺血和介入并发症是有益的。目前治疗ACS和经皮冠状动脉介入治疗（percutaneous coronary intervention,PCI）指南推荐使用的口服抗血小板药物包括氯吡格雷、替格瑞洛、普拉格雷联合阿司匹林双重抗血小板治疗预防复发性缺血事件。本文对新型P2Y12受体抑制剂替格瑞洛的药代动力学和药效学特点以及在ACS患者中的循证医学证据作一介绍。     

Ticagrelor in modern cardiology - an up-to-date review of most important aspects of ticagrelor pharmacotherapy

Introduction: Ticagrelor is a first drug of a new chemical class cyclopentyltriazolopyrimidines. It is an antiplatelet agent with a unique mechanism of action, allowing a direct and reversible competitive inhibition of P2Y₁₂ receptor. According to newest guidelines, it is recommended for prevention of thrombotic events in patients with acute coronary syndromes. Moreover, it is preferred over clopidogrel, an older generation antiplatelet drug, and therefore gains more interest in modern cardiology and vascular medicine.

Areas covered: This review is a comprehensive and thorough summary of the most important findings on ticagrelor. Pharmacokinetics, pharmacogenetics, drug-drug interactions, adverse effects, efficacy in specific patient populations and off-label properties of ticagrelor are discussed in this paper. Moreover, the results from pivotal clinical trials are presented.

Expert opinion: Introduction of ticagrelor, a first directly-acting and reversible P2Y₁₂ inhibitor, gave some new possibilities as the efficacy of older drugs was often insufficient. Despite some drawbacks, such as a risk of bleeding events or dyspnea, a rapid onset of action, consistency in the antiplatelet effect and reports on pleiotropic properties make this drug a promising candidate for a first-choice antiplatelet agent in patients with acute coronary events.     

Pharmacokinetic, pharmacodynamic and pharmacogenetic profile of the oral antiplatelet agent ticagrelor

Acute coronary syndromes (ACS) remain life-threatening disorders associated with high morbidity and mortality, despite advances in treatment over the last decade. Adenosine diphosphate-induced platelet activation via P2Y(12) receptors plays a pivotal role in the pathophysiology of ACS. The current standard of treatment involves dual antiplatelet therapy with aspirin (acetylsalicylic acid) and the thienopyridine clopidogrel. Numerous studies and wide use in clinical practice have established the value of this approach in the treatment of ACS. However, clopidogrel treatment has a number of limitations, including a delayed onset of action due to the need for metabolic activation, variable and reduced antiplatelet effects in patients with certain genotypes, and prolonged recovery of platelet function due to irreversible P2Y(12) receptor binding. Prasugrel, a new thienopyridine, has demonstrated more consistent inhibition of platelet aggregation (IPA) than clopidogrel, although this thienopyridine also requires metabolic activation and treatment is associated with a significantly increased risk of life-threatening and fatal bleeding. The recently approved oral antiplatelet agent ticagrelor has the potential to overcome some of the limitations of current therapy due to its unique pharmacokinetic and pharmacodynamic profiles. It is a member of a new chemical class, the cyclopentyltriazolopyrimidines, and is a potent P2Y(12) receptor antagonist. Ticagrelor is rapidly absorbed, with a median time to maximum concentration of 1.3-2.0 hours. Ticagrelor does not require metabolic activation to an active form and binds rapidly and reversibly to the P2Y(12) receptor. As well as exerting effects via platelet P2Y(12) receptors, ticagrelor may confer additional benefits via inhibition of non-platelet P2Y(12) receptors. The pharmacokinetic profile of ticagrelor is not significantly affected by age, gender or administration with food, nor by prior treatment with, or responsiveness to, clopidogrel. Ticagrelor is primarily metabolized via the cytochrome P450 (CYP) 3A4 enzyme, rapidly produces plasma concentration-dependent IPA that is greater and more consistent than that observed with clopidogrel, and can also enhance platelet inhibition and overcome non-responsiveness in patients previously treated with clopidogrel. Importantly, the pharmacodynamic characteristics of ticagrelor are not influenced by CYP2C19 and ABCB1 genotypes. This article summarizes our current knowledge regarding the pharmacokinetic, pharmacodynamic and pharmacogenetic profile of ticagrelor.     

Triple antithrombotic therapy in patients with atrial fibrillation who have undergone percutaneous coronary intervention with stent implantation

Purpose The efficacy and safety of triple antithrombotic therapy in patients with atrial fibrillation (AF) who undergo percutaneous coronary intervention (PCI) with stent implantation are reviewed. Summary A systematic literature search of PubMed, EMBASE, and International Pharmaceutical Abstracts identified a total of 10 cohort studies and one meta-analysis investigating triple antithrombotic therapy in this patient population. With respect to efficacy, evidence from nonrandomized studies supports the superiority of triple antithrombotic therapy over dual antiplatelet therapy at preventing major adverse cardiac events and all-cause mortality. With respect to safety, the heterogeneous methodology and definitions for bleeding in the studies do not allow for easy interpretation and quantification of bleeding risk. There appears to be qualitative consistency that the rate of bleeding is higher with triple antithrombotic therapy compared with dual antiplatelet therapy. The meta-analysis, as well as a recent large registry data cohort study, demonstrated a twofold increase in the risk of major bleeding with triple antithrombotic therapy. Conclusion The heterogeneous methodology of the available studies does not allow for conclusive interpretation and quantification of the efficacy and safety of triple antithrombotic therapy in patients with AF undergoing PCI with stent implantation compared with dual antiplatelet therapy. Evidence from small cohort studies support the benefit of triple antithrombotic therapy at reducing major adverse cardiac events and all-cause mortality with higher rates of bleeding.     

Antiplatelet Drug Resistance and Drug-Drug Interactions: Role of Cytochrome P450 3A4

Antiplatelet therapy provided pivotal advances in the treatment of cardiovascular disease. Aspirin and thienopyridine, clopidogrel, is currently the treatment of choice in acute coronary syndromes and the prevention of thrombosis after coronary stent implantation. Despite the efficacy of this dual antiplatelet therapy in reduction of adverse coronary events in patients with acute coronary syndromes, complications persist in a subgroup of these patients. Emerging causes of aspirin and clopidogrel resistance may translate to increase risk for recurrent myocardial infarction, stroke, or cardiac related mortality. However, the mechanism of antiplatelet drug resistance remains incompletely characterized, and a sensitive and specific assay of aspirin and clopidogrel effect that reliably predicts treatment failure has not emerged. To date, evidence supporting antiplatelet drug resistance are pharmacokinetic response variability, drug-drug interaction through competitive inhibition a specific enzymatic pathway, genetic variability, and variability in the induction of enzymatic pathway in metabolic activation of prodrugs, like clopidogrel. Further investigation or guidelines are needed to optimize antiplatelet treatment strategies to identify and treat patients resistant to aspirin and/or clopidogrel.     

急性冠脉综合征PCI术后患者双联抗血小板治疗相关不良反应特点及危险因素分析

目的 探讨急性冠脉综合征（ACS）患者接受经皮冠状动脉介入治疗（PCI）后服用替格瑞洛和阿司匹林双联抗血小板治疗出现不良反应的特点及危险因素。方法 前瞻性纳入2018年3月—2018年6月郑州市第七人民医院收治的PCI术后服用替格瑞洛和阿司匹林的ACS患者100例,采用VerifyNow-P2Y12系统检测患者血小板反应性并随访6个月,根据是否发生相关不良反应分为对照组和不良反应组,收集对比两组患者临床基线资料,采用单因素和多因素Logistic回归分析出血和呼吸困难的危险因素。结果 纳入研究的患者未出现不良反应的40例纳入对照组,出现不良反应的60例纳入不良反应组,双联抗血小板治疗相关不良反应发生率60.0%,84例（84.0%）患者存在低血小板反应性。两组患者在年龄、性别、合并疾病、血小板反应性等方面差异不具有统计学意义（P＞0.05）,不良反应组吸烟患者占比明显高于对照组（51.7%vs27.5%,P=0.016）。不良反应主要临床表现为皮肤黏膜出血和轻中度呼吸困难,用药后1个月内出血和呼吸困难发生率显著高于用药后2～6个月（出血发生率：38.0%vs1.0%,P＜0.001;呼吸困难发生率：32.0%vs8.0%,P＜0.001）。多因素Logisitc回归分析显示老年、女性和贫血是双联抗血小板治疗相关出血的独立危险因素（P＜0.05）,吸烟和出血事件是双联抗血小板治疗相关呼吸困难的独立危险因素（P＜0.05）。结论 ACS患者PCI术后双联抗血小板治疗早期出血和呼吸困难发生率高但程度较轻,对于合并危险因素的患者应提前评估、加强监测,最大限度地降低药品不良反应的发生。     

Clopidogrel

Dual antiplatelet therapy with acetylsalicylic acid (aspirin) and clopidogrel is a guideline-recommended standard of care for patients with acute coronary syndromes (ACS) and those who undergo percutaneous coronary intervention (PCI). Despite a large body of clinical evidence obtained from randomized clinical trials and patient registries supporting the efficacy and safety of aspirin plus clopidogrel therapy in these patients, questions concerning the optimal use of dual antiplatelet therapy remain. Widely debated topics pertaining to dual antiplatelet therapy in patients with ACS or undergoing PCI include (i) the appropriate clopidogrel loading dose; (ii) the optimal time to initiate the clopidogrel loading dose; (iii) the optimal duration of dual antiplatelet therapy following ACS or PCI; (iv) impact of variability of platelet response on patient outcomes; and (v) the role of other recommended and emerging P2Y₁₂ antagonists. This review discusses these ongoing controversies regarding the optimal use of dual antiplatelet therapy with aspirin and clopidogrel in patients with ACS or those undergoing PCI.     

Prasugrel during primary percutaneous coronary intervention: evidence from clinical data

Primary percutaneous coronary intervention (PCI) encompassing stent implantation is a mainstay in the management of acute ST-elevation myocardial infarction (STEMI). Despite refinements in techniques and devices, peri- and post-procedural antithrombotic therapy remains pivotal to prevent early and late thrombotic events, without unduly increasing bleeding risk. Concomitant dual antiplatelet therapy with aspirin and clopidogrel has been considered until recently the standard of care in terms of oral antiplatelet agents. However, most recently a novel and more potent thienopyridine, prasugrel, has been tested in randomized trials including patients with STEMI, and subsequently approved for clinical practice in Europe and North America. Despite its potent antithrombotic effect, prasugrel also carries a statistically significant increase in the risk of bleeding, especially in the elderly, those with low body weight, and previous stroke or transient ischemic attack. Thus, the use of prasugrel, as well as that of clopidogrel or ticagrelor, should best be individualized to maximize clinical benefits and minimize hazards.     

Ticagrelor for the treatment of arterial thrombosis

Importance of the field: High platelet reactivity has been linked to recurrent ischemic events in patients treated with conventional dual antiplatelet therapy, in patients with arterial diseases and particularly in patients treated with coronary artery stenting. The limitations of clopidogrel have served as a major rationale for the development of new P2Y₁₂ blockers that have superior pharmacodynamic profiles uninfluenced by concomitant therapies or specific genotypes. Ticagrelor is the first direct-acting reversibly binding oral P2Y₁₂ receptor antagonist. Extensive Phase II investigations have addressed the pharmacokinetic, pharmacodynamic and safety-related properties of ticagrelor compared with clopidogrel. The recently completed PLATO trial demonstrated promise for ticagrelor as a major treatment strategy for a wide spectrum of patients with acute coronary syndromes. Ticagrelor is now being reviewed by the FDA as a P2Y₁₂ receptor blocker to treat patients with coronary artery disease and, once accepted, will be in widespread use as an antiplatelet agent. Thus, it is both appropriate and timely to review available data and provide a comprehensive review of ticagrelor.

Areas covered in this review: We discuss the rationale for the development of ticagrelor, a reversible and potent P2Y₁₂ receptor blocker. The data regarding ticagrelor based on preclinical and clinical studies are examined. We researched articles about ‘AZD6140’ and ‘ticagrelor’ in PubMed from 2006 to 2010 and also reviewed data presented at recent cardiology meetings.

What the reader will gain: This is an updated and comprehensive review of ticagrelor. The advantages and disadvantages of ticagrelor and available P2Y₁₂ receptor blockers such as clopidogrel and prasugrel are discussed, thus providing a clear picture to readers.

Take home message: Ticagrelor has an important role as an antiplatelet agent in the settings of acute coronary syndrome and percutaneous coronary intervention and once accepted will be in widespread use.     

Antithrombotic strategies for preventing long-term major adverse cardiovascular events in patients with non-valvular atrial fibrillation who undergo percutaneous coronary intervention

Introduction: Balancing the risk of recurrent ischemia and bleeding among patients with non-valvular atrial fibrillation who undergo percutaneous coronary intervention (PCI) is challenging. Postprocedural antithrombotic therapy aims to reduce the risk related to coronary artery disease, stent placement, and atrial fibrillation, with acceptable risks of bleeding.

Areas covered: This review summarizes evidence and recommendations related to long-term antithrombotic strategies in such patients. An overview of the findings from recent meta-analyses and select observational studies is provided, and important completed and ongoing randomized trials are described in detail. Recommendations pertaining to treatment intensity and duration, including the choice of specific anticoagulant and antiplatelet agents, are given.

Expert opinion: Triple therapy (oral anticoagulation with dual antiplatelet therapy) is associated with an increased bleeding risk compared with double therapy (oral anticoagulation with a single antiplatelet agent), but double therapy does not appear to be associated with an increased risk of recurrent ischemia or death. Completed trials make a compelling case for double therapy with clopidogrel, not aspirin, when compared with full-intensity triple antithrombotic therapy. We believe that double therapy with an anticoagulant and clopidogrel should generally be favored instead of triple antithrombotic therapy.