ticagrelor and Cardiovascular-Diseases

The aim of this study was to evaluate the efficacy and safety of antithrombotic regimens and their combinations in preventing thrombotic incidents in patients with stable atherosclerotic cardiovascular disease (S-ASCVD).. A systematic literature search was conducted in the PubMed, Embase, Cochrane Library, Scopus, and Google Scholar databases. The primary comprehensive endpoint was a major adverse cardiovascular event (MACE) composite of cardiovascular death, stroke, or myocardial infarction, while the secondary endpoints were cardiovascular death, all-cause stroke, ischemic stroke, myocardial infarction, and all-cause death. The safety endpoint was major bleeding. Bayesian network meta-regression analysis in R software was used to calculate the final effect size and to correct for the effect of follow-up time on the outcome effect size.. Twelve studies reporting 122,190 patients with eight antithrombotic regimens were included in this systematic review. For the primary composite endpoint, low-dose aspirin plus clopidogrel 75 mg (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.33-0.87) and low-dose aspirin plus rivaroxaban 2.5 mg twice daily (HR 0.53, 95% CI 0.34-0.82) showed significantly better efficacy than clopidogrel monotherapy, and the efficacy was comparable among the first two regimens. Unfortunately, none of the active regimens significantly decreased all-cause death, cardiovascular death branch, and all-cause stroke as part of the secondary endpoints. Low-dose aspirin plus ticagrelor 90 mg twice daily (HR 0.81, 95% CI 0.69-0.94) and low-dose aspirin plus ticagrelor 60 mg twice daily (HR 0.84, 95% CI 0.74-0.95) had a significant advantage in myocardial infarction compared with low-dose aspirin monotherapy, while low-dose aspirin plus 2.5 mg rivaroxaban twice daily (HR 0.62, 95% CI 0.41-0.94) was better than low-dose aspirin in the treatment of ischemic stroke. In the major bleeding branch, low-dose aspirin plus ticagrelor 90 mg twice daily (HR 2.2, 95% CI 1.70-2.90), low-dose aspirin plus ticagrelor 60 mg twice daily (HR 2.1, 95% CI 1.70-2.60), low-dose aspirin plus rivaroxaban 2.5 mg twice daily (HR 1.7, 95% CI 1.30-2.00), and rivaroxaban 5 mg twice daily (HR 1.5, 95% CI 1.20-1.90) showed higher major bleeding risk compared with low-dose aspirin.. Considering MACEs, myocardial infarction, all kinds of stroke, ischemic stroke, and major bleeding, low-dose aspirin plus rivaroxaban 2.5 mg twice daily should be considered the preferred regimen for S-ASCVD patients with low bleeding risk.

Topics: Aspirin; Atherosclerosis; Bayes Theorem; Cardiovascular Diseases; Clopidogrel; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Humans; Ischemic Stroke; Myocardial Infarction; Network Meta-Analysis; Platelet Aggregation Inhibitors; Regression Analysis; Rivaroxaban; Stroke; Ticagrelor

The worldwide prevalence of chronic kidney disease (CKD) has significantly increased in the past decades. Scientific reports have shown CKD to be an enhancing risk factor for the development of cardiovascular disease (CVD), which is the leading cause of premature death in patients with CKD. Clinical practice guidelines are ambiguous in view of the use of antiplatelet drugs in patients with CKD because patients with moderate-to-severe CKD were often excluded from clinical trials evaluating the efficacy and safety of anticoagulants and antiplatelet agents. In this analysis, we aimed to systematically assess the adverse cardiovascular and bleeding outcomes that were observed with ticagrelor versus clopidogrel use in patients with CKD and cardiovascular disease.. Electronic databases including Web of Science, Google Scholar, http://www.. gov , Cochrane database, EMBASE, and MEDLINE were carefully searched for English-based articles comparing ticagrelor with clopidogrel in patients with CKD. Adverse cardiovascular outcomes and bleeding events were the endpoints in this study. The latest version of the RevMan software (version 5.4) was used to analyze the data. Risk ratios (RR) with 95% confidence intervals (CI) were used to represent the data post analysis.. A total of 15,664 participants were included in this analysis, whereby 2456 CKD participants were assigned to ticagrelor and 13,208 CKD participants were assigned to clopidogrel. Our current analysis showed that major adverse cardiac events (MACEs) (RR: 0.85, 95% CI: 0.71-1.03; P = 0.09), all-cause mortality (RR: 0.82, 95% CI: 0.57- 1.18; P = 0.29), cardiovascular death (RR: 0.83, 95% CI: 0.56-1.23; P = 0.35), myocardial infarction (RR: 0.87, 95% CI: 0.70-1.07; P = 0.19), ischemic stroke (RR: 0.80, 95% CI: 0.58-1.11; P = 0.18), and hemorrhagic stroke (RR: 1.06, 95% CI: 0.38-2.99; P = 0.91) were not significantly different in CKD patients who were treated with ticagrelor versus clopidogrel. Thrombolysis in myocardial infarction (TIMI)-defined minor (RR: 0.89, 95% CI: 0.52-1.53; P = 0.68) and TIMI major bleeding (RR: 1.10, 95% CI: 0.69-1.76; P = 0.67) were also not significantly different. However, bleeding defined according to the academic research consortium (BARC) bleeding type 1 or 2 (RR: 1.95, 95% CI: 1.13-3.37; P = 0.02) and BARC bleeding type 3 or 5 (RR: 1.70, 95% CI: 1.17-2.48; P = 0.006) were significantly higher with ticagrelor.. When compared with clopidogrel, even though ticagrelor was not associated with higher risk of adverse cardiovascular outcomes in these patients with CKD, it was associated with significantly higher BARC bleeding. Therefore, the safety outcomes of ticagrelor still require further evaluation in patients with CKD. Nevertheless, this hypothesis should only be confirmed with more powerful results that could usually only be achieved using large-scale randomized trials.

Topics: Acute Coronary Syndrome; Cardiovascular Diseases; Clopidogrel; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Renal Insufficiency, Chronic; Ticagrelor; Treatment Outcome

Antiplatelet medications remain a cornerstone of therapy for atherosclerotic cardiovascular and cerebrovascular diseases. In primary prevention (patients with cardiovascular risk factors but no documented events, symptoms or angiographic disease), there is little evidence of benefit of any antiplatelet therapy, and such therapy carries the risk of excess bleeding. Where there is documented disease (secondary prevention), stable patients benefit from long-term antiplatelet monotherapy, aspirin being first choice in those with coronary heart disease and clopidogrel in those with cerebrovascular disease; moreover, recent evidence shows that low-dose rivaroxaban in combination with aspirin confers added benefit, in patients with stable cardiovascular and peripheral arterial disease. In patients with acute cerebrovascular disease, aspirin combined with clopidogrel reduces subsequent risk, while in acute coronary syndrome, dual antiplatelet therapy comprising aspirin and a P2Y

Topics: Acute Coronary Syndrome; Aspirin; Cardiovascular Diseases; Clopidogrel; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor

Cardiometabolic diseases lead to vascular complications, which cause increasing morbidity and mortality worldwide. The underlying mechanisms are multifactorial and complex but may involve altered purinergic signaling that significantly contributes to cardiovascular dysfunction. Ticagrelor is a successful purinergic drug directly targeting ADP-mediated P2Y

Topics: Adenosine; Adenosine Triphosphate; Animals; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Erythrocytes; Humans; Purinergic Agonists; Signal Transduction; Ticagrelor

Dual antiplatelet therapy (DAPT) and subsequent P2Y

Topics: Acute Coronary Syndrome; Cardiovascular Diseases; Drug Therapy, Combination; Dual Anti-Platelet Therapy; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Treatment Outcome

Acute coronary syndrome (ACS) is a major cause of morbidity and mortality in the United States with an annual incidence of approximately 1 million. Dual antiplatelet therapy (DAPT), consisting of aspirin and a P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel) reduces cardiovascular event rates after ACS.. In 2016, the updated guidelines from the American College of Cardiology/American Heart Association (ACC/AHA) recommended aspirin plus a P2Y12 inhibitor for at least 12 months for patients with ACS. Since these recommendations were published, new randomized clinical trials have studied different regimens and durations of antiplatelet therapy. Recommendations vary according to the risk of bleeding. If bleeding risk is low, prolonged DAPT may be considered, although the optimal duration of prolonged DAPT beyond 1 year is not well established. If bleeding risk is high, shorter duration (ie, 3-6 months) of DAPT may be reasonable. A high risk of bleeding traditionally is defined as a 1-year risk of serious bleeding (either fatal or associated with a ≥3-g/dL drop in hemoglobin) of at least 4% or a risk of an intracranial hemorrhage of at least 1%. Patients at higher risk are 65 years old or older; have low body weight (BMI <18.5), diabetes, or prior bleeding; or take oral anticoagulants. The newest P2Y12 inhibitors, prasugrel and ticagrelor, are more potent, with high on-treatment residual platelet reactivity of about 3% vs 30% to 40% with clopidogrel and act within 30 minutes compared with 2 hours for clopidogrel. Clinicians should avoid prescribing prasugrel to patients with a history of stroke or transient ischemic attack because of an increased risk of cerebrovascular events (6.5% vs 1.2% with clopidogrel, P = .002) and should avoid prescribing it to patients older than 75 years or who weigh less than 60 kg. The ISAR-REACT-5 trial found that prasugrel reduced rates of death, myocardial infarction, or stroke at 1 year compared with ticagrelor among patients with ACS undergoing percutaneous coronary intervention (9.3% vs 6.9%, P = .006) with no significant difference in bleeding. Recent trials suggested that discontinuing aspirin rather than the P2Y12 inhibitor may be associated with better outcomes.. Dual antiplatelet therapy reduces rates of cardiovascular events in patients with acute coronary syndrome. Specific combinations and duration of dual antiplatelet therapy should be based on patient characteristics-risk of bleeding myocardial ischemia.

Topics: Acute Coronary Syndrome; Administration, Oral; Aspirin; Cardiovascular Diseases; Clopidogrel; Drug Therapy, Combination; Humans; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor

Topics: Cardiovascular Diseases; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Secondary Prevention; Ticagrelor

Cardiovascular complications remain the main cause of mortality and morbidity in diabetes. This is related to advanced vascular pathology in this population, together with an enhanced thrombotic environment. The increased risk in thrombosis is secondary to platelet hyper-reactivity and increased levels and/or altered activity of coagulation factors. The current review is focused on the role of antiplatelet agents in modulating the thrombotic milieu in diabetes and improving vascular outcome in this high-risk population. We review the latest evidence for the use of aspirin in primary vascular prevention together with long-term treatment with this agent for secondary prevention. We also discuss the effects of the various P2Y

Topics: Aspirin; Cardiovascular Diseases; Clopidogrel; Diabetes Mellitus; Humans; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Primary Prevention; Secondary Prevention; Thrombosis; Ticagrelor

Antithrombotic treatment is a key component of secondary prevention following acute coronary syndromes (ACS). Although dual antiplatelet therapy is standard therapy post-ACS, duration of treatment is the subject of ongoing debate. Prolonged dual antiplatelet therapy in high-risk patients with history of myocardial infarction reduced the risk of recurrent myocardial infarction, stroke or cardiovascular death. Similarly, in patients with stable coronary artery disease, two-thirds of whom had a history of myocardial infarction, dual antithrombotic therapy with very-low-dose rivaroxaban and aspirin also resulted in improved ischaemic outcomes. In the absence of head-to-head comparison, choosing the most appropriate treatment strategy can be challenging, particularly when it comes to balancing the risks of ischaemia and bleeding. We aim to review the evidence for currently available antithrombotic treatments and provide a practical algorithm to aid the decision-making process.

Topics: Acute Coronary Syndrome; Aged; Algorithms; Aspirin; Cardiovascular Diseases; Coronary Artery Disease; Decision Making; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Risk; Rivaroxaban; Secondary Prevention; Stroke; Ticagrelor

The pharmacological and clinical differences of the three recommended oral P2Y

Topics: Adenosine Monophosphate; Administration, Intravenous; Administration, Oral; Blood Platelets; Cardiovascular Diseases; Clinical Decision-Making; Clopidogrel; Drug Substitution; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Ticagrelor; Treatment Outcome

Background As reports on the influence of cigarette smoking, an important cardiovascular risk factor, on platelet ADP -P2Y12 receptor inhibitors lack consistency, we aimed to assess the effectiveness and safety of platelet ADP -P2Y12 receptor inhibitors influenced by smoking status. Methods and Results PubMed, Web of Science, EMBASE , Clinical Trials, and the Cochrane Library were searched from inception until June 2018. Among the 5076 citations retrieved, 22 studies, including 163 011 patients with or without percutaneous coronary intervention, were included for meta-analysis. Compared with nonsmokers within the first year of follow-up, the reductions of stroke and major adverse cardiovascular event rate were 18% ( P=0.008) and 26% ( P=0.02), respectively. A 20% reduction in stroke ( P=0.02) and a 34% reduction in major adverse cardiovascular event ( P=0.0001) rates were observed in smoking patients without percutaneous coronary intervention. No significant difference was observed in clinical outcome rates among prasugrel, ticagrelor, and clopidogrel in different smoking status. No significant difference was found in myocardial infarction and bleeding event incidence between current smokers and nonsmokers. Conclusions We concluded that current smokers had a lower incidence of major adverse cardiovascular events and stroke events than did nonsmokers, particularly in the early period (1 year) and among patients without percutaneous coronary intervention. However, because of the lack of original adjusted data, smoker's paradox still needs to consider the impact of age and other covariates. Thus, a differential risk-benefit evaluation should be considered, according to different smoking status, patient conditions, and therapy time points.

Topics: Acute Coronary Syndrome; Aged; Cardiovascular Diseases; Cigarette Smoking; Clopidogrel; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Stroke; Ticagrelor; Treatment Outcome

De-escalation from ticagrelor to clopidogrel in acute coronary syndrome (ACS) may occur for a variety of reasons, including side effects (bleeding and non-bleeding) and costs. This study sought to assess the prevalence of de-escalation from ticagrelor to clopidogrel and the occurrence of adverse clinical outcomes following de-escalation. We conducted a systematic review of clinical trials and real-world studies in ACS patients treated with ticagrelor. Real-world data on the prevalence of de-escalation during hospitalization or at discharge, after hospital discharge, and during the whole study period were included for meta-analysis. Major adverse cardiovascular events (MACE) and bleeding events occurring after de-escalation were also assessed. A total of 12 studies were eligible for meta-analysis of the prevalence of de-escalation. De-escalation from ticagrelor to clopidogrel therapy occurred with a mean prevalence of 19.8% [95% confidence interval (CI) 11.2-28.4%]. De-escalation occurred more frequently in-hospital or at discharge than after hospital discharge (23.7% vs. 15.8%). For assessment of clinical outcomes, a total of six studies were eligible for meta-analysis. Mean rate of MACE for patients with de-escalation was 2.1% (95% CI 1.1-4.1%) and the rate of major bleeding events was 1.3% (95% CI 0.4-4.5%). In conclusion, de-escalation commonly occurs in real-world practice. Although rates of major cardiovascular and bleeding events in this analysis were generally low, the profile of patients suitable for de-escalation, the impact of de-escalation on adverse clinical outcomes and how this is affected by the timing after index ACS warrants further large-scale investigation.

Topics: Acute Coronary Syndrome; Cardiovascular Diseases; Clopidogrel; Hemorrhage; Hospitalization; Humans; Patient Discharge; Prevalence; Ticagrelor

Dual antiplatelet therapy with aspirin and clopidogrel are recommended as adjuncts to fibrinolytic-treated patients with ST-elevation myocardial infarction (STEMI). However, the role of switching to ticagrelor within 24 h of fibrinolytics compared with clopidogrel continuation in this setting is uncertain. Hence, we conducted a comprehensive search of electronic databases for all randomized clinical trials (RCTs) that evaluated the safety and efficacy of ticagrelor versus clopidogrel after fibrinolytic therapy in patients with STEMI. A random-effects model was used to calculate the risk ratios (RRs) and 95% confidence intervals (CIs). A total of 5 RCTs that evaluated the efficacy of ticagrelor post-fibrinolysis were identified. We included 3 RCTs with 3999 total patients for our meta-analysis. The results showed similar short-term clinical outcomes between ticagrelor and clopidogrel with regard to rates of Bleeding Academic Research Consortium (BARC) type ≥ 2 bleeding (RR 0.94; 95% CI 0.56-1.60; P = 0.83), major adverse cardiovascular events (RR 0.87; 95% CI 0.49-1.52; P = 0.62), mortality (RR 0.92; 95% CI 0.53-1.59; P = 0.77), myocardial infarction (RR 0.76; 95% CI 0.43-1.36; P = 0.36), and stroke (RR 0.93; 95% CI 0.50-1.73; P = 0.82). Our results demonstrate that in STEMI patients treated with fibrinolytic therapy, switching to ticagrelor was associated with similar bleeding and ischemic outcomes compared with clopidogrel continuation.

Topics: Cardiovascular Diseases; Clopidogrel; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; ST Elevation Myocardial Infarction; Stroke; Survival Analysis; Thrombolytic Therapy; Ticagrelor

Although the rate of cardiovascular disease (CVD)-related mortality has declined over the last decade, it is still the leading cause of mortality in the USA, accounting for over 1.4 million deaths annually. In addition, total direct (primarily hospital admissions) and indirect costs of CVD in the US is over $316 billion annually and is expected to grow to over $918 billion by 2030. Much of the etiology of CVD is due to atherosclerosis and its thrombotic complications, and central to this is the role of platelets. Atherosclerosis is a systemic disease, with meaningful morbidity and mortality when present in the coronary, cerebral, or major peripheral arteries. The recommended antiplatelet therapy differs based on the vascular bed impacted, with the optimal antiplatelet therapy yet to be defined. The PARTHENON program is a series of completed and ongoing phase III clinical trials investigating the efficacy and safety of ticagrelor in atherosclerotic CVD in comparison with established antiplatelet therapy or placebo. The overall aim of the program is to determine if more potent antiplatelet therapy, with different pharmacology, may reduce cardiovascular events in patients with atherosclerotic disease.

Topics: Adenosine; Atherosclerosis; Cardiovascular Diseases; Humans; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Thrombosis; Ticagrelor

Topics: Adenosine; Cardiovascular Diseases; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Hemorrhage; Humans; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Secondary Prevention; Stroke; Ticagrelor

Aspirin and P2Y

Topics: Adenosine; Aspirin; Cardiovascular Diseases; Clopidogrel; Drug Administration Schedule; Drug Dosage Calculations; Drug Interactions; Esomeprazole; Gastrointestinal Hemorrhage; Gene Expression; Humans; Hydrogen-Ion Concentration; Peptic Ulcer; Prasugrel Hydrochloride; Proton Pump Inhibitors; Purinergic Antagonists; Receptors, Purinergic P2Y12; Ticagrelor; Ticlopidine

Aspirin, the first antiplatelet agent, has been around since the 19th century, and is one of the most established drugs in history. With the improvement of coronary interventions in the past few decades, there has been more reliance on oral antiplatelet agents to reduce complications of in-stent restenosis/thrombosis. Clopidogrel was initially introduced in 1997, and within the past seven years, two additional oral antiplatelet agents have been approved by the U.S. Food and Drug Administration. With more potent antiplatelet agents comes increased risks of adverse effects. Physicians of all fields should be aware of the common antiplatelet agents used today, and the basic landmark trials that allowed them to be on the market today. The focus of this review article is to evaluate each oral antiplatelet drug, its brief history, relevant trials, indications and management of complications through evidence based guidelines.

Topics: Adenosine; Administration, Oral; Aspirin; Cardiovascular Diseases; Clopidogrel; Gastrointestinal Hemorrhage; Humans; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Risk Factors; Thrombosis; Ticagrelor; Ticlopidine

Antiplatelet drugs are the cornerstone of therapy in many cardiovascular conditions. With the current success and increased use of transcatheter aortic valve implantation (TAVI), the use of antiplatelet therapy is considered part of the medical therapy for these patients. Clinicians caring for these patients need to have a thorough understanding of the pharmacology, pharmacokinetics, pharmacodynamic, and clinical efficacy and safety of commonly used antiplatelet therapy. While aspirin therapy is widely used, dual antiplatelet therapy with clopidogrel has become part of standard of care. Despite the extensive experience with clopidogrel, there are limitations such as drug interactions, metabolism genetic polymorphisms, and variability in the antiplatelet response. More predictable and more potent antiplatelet agents, prasugrel and ticagrelor, have demonstrated superior reductions in ischemic endpoints as part of dual antiplatelet therapy compared to clopidogrel, but at the cost of more major bleeding in patients with an acute coronary syndrome. Significant research needs to be conducted in the setting of TAVI to help define the optimal antiplatelet regimen.

Topics: Adenosine; Aspirin; Cardiovascular Diseases; Clopidogrel; Humans; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor; Ticlopidine; Transcatheter Aortic Valve Replacement

Type 2 diabetes (T2D) is associated with several abnormalities in haemostasis predisposing to thrombosis. Moreover, T2D was recently connected with a failure in antiplatelet response to clopidogrel, the most commonly used ADP receptor blocker in clinical practice. Clopidogrel high on-treatment platelet reactivity (HTPR) was repeatedly associated with the risk of ischemic adverse events. Patients with T2D show significantly higher residual platelet reactivity on ADP receptor blocker therapy and are more frequently represented in the group of patients with HTPR. This paper reviews the current knowledge about possible interactions between T2D and ADP receptor blocker therapy.

Topics: Adenosine; Adenosine Monophosphate; Blood Platelets; Cardiovascular Diseases; Clopidogrel; Diabetes Mellitus, Type 2; Drug Resistance; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Risk Factors; Ticagrelor; Ticlopidine; Treatment Outcome

Chronic kidney disease has been identified as an independent cardiovascular risk factor. The morbidity and mortality due to cardiovascular disease are higher among chronic kidney disease patients when compared with patients with normal kidney function. Although P2Y12 inhibitors (eg. clopidogrel) are associated with increased survival rates after a myocardial infarction, most of the clinical trials excluded End-Stage Renal Disease (ESRD) patients. Besides, non-responders to P2Y12 inhibitors have been identified as at risk of cardiovascular adverse events and non-responder prevalence is higher among ESRD than in any other population. Recent data questioned the benefits from P2Y12 inhibitors among chronic kidney disease patients. This systematic review aimed to describe pharmacokinetics (PK) and pharmacodynamics (PD) evidence data among 3 widely prescribed P2Y12 inhibitors. Clopidogrel and prasugrel are bioactivated by the cytochromes P450 (CYP) while ticagrelor is already active. PD data used different assays among which the VerifyNow® which showed intravariability before and after dialysis. The potential explanation of modulated PK/PD parameters among ESRD patients will be addressed. Absorption as well as metabolism is diminished in ESRD patients. It could potentially lead to absence of clopidogrel or prasugrel bioactivation or ticagrelor accumulation. Evidence-based recommendation regarding the best option for antiaggregation secondary to percutaneous intervention in this high risk population is still lacking.

Topics: Adenosine; Animals; Cardiovascular Diseases; Clopidogrel; Humans; Kidney Failure, Chronic; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine

Cardiovascular disease and in particular, acute coronary syndromes are one of the principle causes of death in the industrialized countries. In the setting of acute coronary syndromes (both ST - segment or non ST - segment elevation myocardial infarction), platelets aggregation plays a key and central role in their development. Platelets are the mediators of hemostasis at sites of vascular injury, but they also mediate pathologic thrombosis; activated platelets stimulate thrombus formation in response to rupture of an atherosclerotic plaque or endothelial cell erosion promoting atherothrombotic disease. Recent patent relates to the methods and devices for treating atherosclerosis and to prevent in-stent restenosis or thrombosis. Because of the importance of platelets involvement in the initiation and propagation of thrombosis, antiplatelet drugs have a source of research; in the recent past, new antiplatelet drugs (such as ticagrelor) have been studied and placed in the routine therapy. The aim of this paper is to summarize the pharmacological properties and the clinical characteristics of ticagrelor.

Topics: Acute Coronary Syndrome; Adenosine; Animals; Blood Platelets; Cardiovascular Diseases; Humans; Patents as Topic; Platelet Aggregation; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Thrombosis; Ticagrelor

Topics: Adenosine; Aspirin; Benzimidazoles; beta-Alanine; Cardiovascular Diseases; Clopidogrel; Dabigatran; Drug Interactions; Drug Therapy, Combination; Fibrinolytic Agents; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Proton Pump Inhibitors; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticagrelor; Ticlopidine; Warfarin

Antiplatelet therapy is a cornerstone in the treatment of cardiovascular disease to prevent ischemic events. Various tests have become clinically available to measure platelet function after antiplatelet treatment. A wide interpatient variability in the magnitude of platelet inhibition has been demonstrated in numerous studies, especially in response to clopidogrel. Several reasons including clinical, pharmacological and genetic factors have been identified. High on-clopidogrel platelet reactivity has been linked to adverse clinical outcome, in particular to stent thrombosis after percutaneous coronary interventions. New antiplatelet drugs including prasugrel and ticagrelor have been advocated to overcome the limitations of clopidogrel. Several studies addressed the concept of tailored antiplatelet treatment according to the results of platelet function testing. Within this review, we summarize the current status of personalized antiplatelet therapy for cardiovascular disease.

Topics: Adenosine; Cardiovascular Diseases; Clopidogrel; Humans; Piperazines; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Precision Medicine; Thiophenes; Ticagrelor; Ticlopidine; Treatment Outcome

Topics: Adenosine; Cardiovascular Diseases; Clopidogrel; Coronary Artery Disease; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Pyridines; Thiophenes; Ticagrelor; Ticlopidine; Treatment Outcome

Acetylsalicylic acid, or aspirin, is perhaps the most well-studied drug in human history, but controversy persists regarding both optimal dose and its use in the primary prevention of atherothrombotic events. This article reviews the following: the effect of aspirin upon the cyclooxygenase pathway; clinical trials of aspirin for both secondary and primary prevention; prospective and retrospective studies of aspirin dose; the potential interaction between aspirin and ticagrelor; and the concept of aspirin resistance. It concludes with a review of major society guidelines regarding aspirin and offers a perspective on the evidence-based use of aspirin in clinical practice.

Topics: Adenosine; Aspirin; Cardiovascular Diseases; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Interactions; Drug Resistance; Evidence-Based Medicine; Humans; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Primary Prevention; Secondary Prevention; Ticagrelor

For several years, clopidogrel plus aspirin has been the dual antiplatelet therapy (DAPT) of choice for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) with stent implantation. More recently, prasugrel and ticagrelor have demonstrated greater efficacy than clopidogrel. In TRITON-TIMI 38, the risk of TIMI major bleeding unrelated to coronary artery bypass graft (CABG) surgery was similar for prasugrel and clopidogrel after excluding subgroups with increased bleeding risk (previous stroke or transient ischemic event; age ≥75 years; weight <60 kg). In the PLATO trial, rates of TIMI major bleeding were similar for ticagrelor and clopidogrel, but ticagrelor was associated with a significantly higher rate of non-CABG-related TIMI major bleeding. Current evidence suggests that prasugrel or ticagrelor plus aspirin should be the DAPT of choice in patients with ACS undergoing PCI unless they are at particularly high risk of bleeding. No studies have yet compared prasugrel and ticagrelor in ACS patients, however prasugrel and ticagrelor have different side effect profiles, and the choice of agent should be made either as a default choice and/or on an individual patient basis. Ongoing trials in ACS patients will increase the evidence base for new P2Y(12) receptor inhibitors and help to establish the most effective DAPT regimens.

Topics: Adenosine; Cardiovascular Diseases; Clopidogrel; Humans; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Stents; Thiophenes; Ticagrelor; Ticlopidine; Treatment Outcome

Platelet adhesion, activation and aggregation play a pivotal role in atherothrombosis. Intracoronary atherothrombosis is the most common cause of the development of acute coronary syndrome (ACS), and plays a central role in complications occurring around percutaneous coronary intervention (PCI) including recurrent ACS, procedure-related myocardial infarction or stent thrombosis. Inhibition of platelet aggregation by medical treatment impairs formation and progression of thrombotic processes and is therefore of great importance in the prevention of complications after an ACS or around PCI. An essential part in the platelet activation process is the interaction of adenosine diphosphate (ADP) with the platelet P2Y12 receptor. The P2Y12 receptor is the predominant receptor involved in the ADP-stimulated activation of the glycoprotein IIb/IIIa receptor. Activation of the glycoprotein IIb/IIIa receptor results in enhanced platelet degranulation and thromboxane production, and prolonged platelet aggregation. The objectives of this review are to discuss the pharmacological limitations of the P2Y12 inhibitor clopidogrel, and describe the novel alternative P2Y12 inhibitors prasugrel and ticagrelor and the clinical implications of the introduction of these new medicines.

Topics: Adenosine; Cardiovascular Diseases; Clinical Trials as Topic; Clopidogrel; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Thiophenes; Ticagrelor; Ticlopidine

The convention of loading with clopidogrel 300 mg before coronary intervention may be due for change, but to what? Newer antiplatelet agents may offer better outcomes, at some financial cost. Disappointingly for decision-making clinicians, head-to-head comparisons for the newer alternatives are not available. We systematically review and compare the three alternative strategies: clopidogrel 600 mg, prasugrel and ticagrelor. A total of 14 studies have compared these strategies with the long-standing convention of 300 mg. Throughout this analysis, we consistently report incremental costs and consequences using clopidogrel 300 mg as the reference strategy. Risk ratios for major adverse cardiovascular events at 30 days were 0.74 (95% confidence interval 0.66-0.82, p=0.002) for clopidogrel 600 mg, 0.78 (0.69-0.89; p<0.001) for prasugrel and 0.88 (0.77-1.00; p=0.045) for ticagrelor. All-cause mortality risk ratios were 0.87 (0.74-1.03) with clopidogrel 600 mg, 0.95 (0.78-1.16) with prasugrel and 0.78 (0.69-0.89) with ticagrelor. TIMI major bleeding has risk ratio 0.92 (0.74-1.16; p=0.85) with clopidogrel 600 mg, 1.32 (1.03-1.16; p=0.03) with prasugrel and 1.25 (1.03-1.53; p=0.03) with ticagrelor. Incremental cost for the first year was £0.32 (US$0.50, €0.40) with clopidogrel 600 mg, £608 (US$977, €709) with prasugrel and £665 (US$1068, €775) with ticagrelor. All three strategies have shown a similar reduction in MACE at 30 days by comparison to clopidogrel 300 mg. All three strategies offer progressive benefit, most marked with Ticagrelor. Whether this is worth both the risk of non-compliance with twice-a-day dosing in real-life patients lacking the same motivation as their trial-volunteer counterparts, and the 2000-fold difference in incremental cost, is the remaining matter for debate.

Topics: Adenosine; Animals; Cardiovascular Diseases; Clopidogrel; Hemorrhage; Humans; Piperazines; Prasugrel Hydrochloride; Thiophenes; Ticagrelor; Ticlopidine

Over the last two decades or more, anti-platelet therapy has become established as a cornerstone in the treatment of patients with ischaemic cardiovascular disease, since such drugs effectively reduce arterial thrombotic events. The original agent used in this context was aspirin (acetylsalicylic acid) but, with the advent of adenosine diphosphate (ADP) receptor antagonists, the use of dual anti-platelet therapy has resulted in further improvement in cardiovascular outcomes when compared with aspirin alone. The first group of platelet ADP receptor antagonists to be developed was the thienopyridine class, which comprise inactive pro-drugs that require in vivo metabolism to their active metabolites before exerting their inhibitory effect on the P2Y(12) receptor. Clopidogrel has been the principal ADP receptor antagonist in use over the past decade, but is limited by variability in its in vivo inhibition of platelet aggregation (IPA). The pharmacokinetics of clopidogrel are unpredictable due to their vulnerability to multiple independent factors including genetic polymorphisms. Expression of the 3435T/T genetic variant encoding the MDR1 gene for the P-glycoprotein efflux transporter results in a significantly reduced maximum drug concentration and area under the plasma concentration-time curve as intestinal absorption of clopidogrel is reduced; and the expression of the mutant *2 allele of CYP2C19 results in similar pharmacokinetic effects as the two cytochrome P450 (CYP)-mediated steps required for the production of the active metabolite of clopidogrel are impaired. These variable pharmacokinetics lead to erratic pharmacodynamics and cannot reliably be overcome with increased dosing. Both prasugrel, a third-generation thienopyridine, and ticagrelor, a cyto-pentyl-triazolo-pyrimidine, have more predictable pharmacokinetics and enhanced pharmacodynamics than clopidogrel. Neither appears to be affected by the same genetic polymorphisms as clopidogrel; prasugrel requires only a single CYP-mediated step to produce its active metabolite and ticagrelor is not a pro-drug. Enhanced IPA by both prasugrel and ticagrelor is achieved at the expense of increased major bleeding, although this is partially mitigated in the case of ticagrelor due to its reversible IPA. However, the reversible binding of ticagrelor to the P2Y(12) receptor requires a twice-daily dosing regimen. Due to limited data from clinical studies, the use of prasugrel is currently restricted to individu

Topics: Adenosine; Cardiovascular Diseases; Clopidogrel; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticagrelor; Ticlopidine

Since novel antiplatelet treatments (prasugrel, ticagrelor, high-dose clopidogrel) have been predominantly tested against standard-dose clopidogrel, data on direct comparisons between these therapies are scarce. We therefore indirectly compared their efficacy and safety in patients undergoing percutaneous coronary intervention. Electronic databases were searched systematically to identify head-to-head randomised controlled trials (RCTs). Network meta-analysis was performed using generalised linear mixed models with adjustment for length of follow-up. Findings were corroborated by mixed treatment comparison through Bayesian methods. Fourteen RCTs were identified and included in the analysis (high- vs. standard-dose clopidogrel: 9 trials, prasugrel vs. high-dose clopidogrel: 2 trials, prasugrel vs. standard-dose clopidogrel: 2 trials, ticagrelor vs. standard-dose clopidogrel: 1 trial). No significant differences were found for efficacy outcomes except for stent thrombosis favouring prasugrel (vs. ticagrelor: odds ratio [OR] 0.63, 95% confidence interval [CI]: 0.42, 0.94; vs. high-dose clopidogrel: OR 0.70, 95%CI: 0.48, 1.01). Prasugrel exhibited a similar bleeding risk as high-dose clopidogrel, but more major (OR 1.43, 95%CI 1.07, 1.90) and major or minor bleeding (OR 1.36, 95%CI 1.09, 1.69) compared to ticagrelor. Ticagrelor was also associated with less major or minor bleeding compared to high-dose clopidogrel (OR 0.81, 95%CI 0.69, 0.96). No differences were seen for non CABG-related major bleeding between the three strategies. Results were corroborated in a subgroup analysis comprising only patients with acute coronary syndromes. In the absence of head-to-head clinical trials, network meta-analysis suggests potentially relevant differences in efficacy and bleeding risk among novel antiplatelet treatments and may thereby advance understanding of their differential therapeutic properties.

Topics: Acute Coronary Syndrome; Adenosine; Angioplasty; Cardiovascular Diseases; Clopidogrel; Hemorrhage; Humans; Odds Ratio; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Risk; Stents; Thiophenes; Ticagrelor; Ticlopidine; Treatment Outcome

Although there are many new and effective anti-P2Y(12) drugs available, clopidogrel in its original or generic forms will probably remain the most widely used and cheaper option. As clopidogrel is a pro-drug, there is marked heterogeneity in drug responsiveness between individuals and lack of responsiveness is associated with poorer clinical outcomes. Various platelet function and genetic tests are now available for potentially measuring whether clopidogrel effectively inhibits platelet function. Monitoring of P2Y(12) inhibition and/or identification of loss of function cytochrome P-450 genotypes could, therefore, offer the potential of tailoring therapy by identifying poor responders to clopidogrel and optimizing the levels of platelet inhibition using, for example, alternative drugs such as prasugrel or ticagrelor. The question remains whether any of these tests have prognostic utility with a defined therapeutic window to reliably identify hypo or hyper-responsive patients who may have an increased risk of thrombosis or bleeding, respectively? Once such patients are identified, can the tests then be subsequently used to demonstrate a change or improvement in platelet reactivity by using alternative therapies and equate this with improved clinical outcome? In this review, we describe an overview of the current platelet and genetic tests available and discuss whether these tests will ever become used routinely.

Topics: Adenosine; Blood Platelets; Cardiovascular Diseases; Clopidogrel; Cytochrome P-450 Enzyme System; Humans; Piperazines; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Precision Medicine; Prodrugs; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Thiophenes; Ticagrelor; Ticlopidine

Despite improved clinical outcomes from dual anti-platelet therapy with aspirin plus the CYP12 ADP receptor antagonist clopidogrel in patients undergoing coronary revascularisation, ex-vivo platelet function testing consistently reveals a proportion of patients with apparent resistance or non-response to clopidogrel loading and maintenance therapy who are at increased risk of coronary thrombosis. Treatment regimens using the newer CYP12 antagonists prasugrel and ticagrelor demonstrate improved ex-vivo platelet inhibition and superior clinical efficacy in large-scale clinical trials-even in patients demonstrating clopidogrel resistance. However, improved efficacy comes at the cost of an increased overall risk of bleeding for both drugs. Further analysis of the outcomes from large scale clinical studies suggests that individual patient sub-groups differ both in their liklehood of bleeding with newer anti-platelet agents and with regard to efficacy outcomes. Therefore when deciding anti-platelet regimens in suspected acute coronary syndrome, particular consideration must be given to patient's risk of thrombosis (STEMI, previous stent thrombosis), the procedure (complex PCI, thrombus in-situ, strategy of pre-treatment), and factors affecting safety (patient age, patient weight, previous stroke, liklehood of surgical revascularisation). Placing the focus on individualised patient risk-benefit assessment with appropriate use of platelet function testing when indicated, in combination with the ongoing assessment of prasugrel and ticagrelor in larger numbers of patients should be the key strategies governing use of dual anti-platelet therapy.

Topics: Adenosine; Animals; Blood Platelets; Cardiovascular Diseases; Clopidogrel; Drug Design; Drug Resistance; Drug Therapy, Combination; Evidence-Based Medicine; Hemorrhage; Humans; Piperazines; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Predictive Value of Tests; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Risk Assessment; Risk Factors; Thiophenes; Ticagrelor; Ticlopidine

To summarize the pharmacokinetic and pharmacodynamic properties of ticagrelor, a selective P2Y12 receptor antagonist, and evaluate its role in the treatment of patients with acute coronary syndromes (ACS).. A literature search was conducted in MEDLINE (1966-November 2009), International Pharmaceutical Abstracts (1970-November 2009), and EMBASE (1990-November 2009) using the MeSH terms and key words AZD6140, ticagrelor, P2Y12 receptor antagonist, cardiovascular disease, ACS, atherothrombosis, and platelets.. Selected studies evaluated the pharmacology, pharmacokinetics, pharmacodynamics, safety, and efficacy of ticagrelor for the treatment of ACS.. Ticagrelor selectively and reversibly blocks the P2Y12 receptor, inhibiting platelet aggregation and preventing amplification of platelet activation. Optimal dosing strategy as determined by ticagrelor's pharmacokinetic and pharmacodynamic profile is a loading dose of 180 mg followed by 90 mg by mouth twice daily. At these doses, greater platelet inhibition is observed with ticagrelor as compared to clopidogrel 75 mg once daily in both clopidogrel-experienced and -naïve patients. Studies in patients experiencing ACS concluded that ticagrelor reduced the rate of cardiovascular death, nonfatal myocardial infarction, stent thrombosis, and overall mortality compared to clopidogrel without increasing major bleeding when administered with standard therapy for ACS. There was no significant difference in the risk of stroke with ticagrelor compared to clopidogrel; however, intracranial bleeding was more common with ticagrelor. Ticagrelor is well tolerated; however, minor bleeding, dyspnea, hypotension, nausea, and ventricular pauses were reported more frequently than with clopidogrel. Reversible inhibition with ticagrelor may allow for more rapid surgical intervention after discontinuation, suggesting greater flexibility in treatment of ACS.. Ticagrelor's improved pharmacokinetic and pharmacodynamic profile builds upon the limitations of currently available P2Y12 receptor antagonists. Ticagrelor represents a promising approach for the prevention of cardiovascular events in patients with ACS.

Topics: Acute Coronary Syndrome; Adenosine; Animals; Cardiovascular Diseases; Clopidogrel; Humans; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Antagonists; Receptors, Purinergic P2Y12; Ticagrelor; Ticlopidine

The role of antiplatelet therapy in the management of coronary artery disease and its sequalae is of great significance. Acetil Salycilic Acid (ASA) has continued to dominate the field as a potent antiplatelet agent, due to its ease of use and cost effectiveness. In addition to this, clopidogrel has also been widely used with better long term administration results in patients with atherosclerotic disease. However, interpatient variability and resistance to clopidogrel has opened the doors for further investigative research to find another agent which potentially meets the pharmacokinetic demands whilst having a satisfactory safety profile. Prasugrel and other novel nonthienopyridine derivatives are currently under investigation, with previous trials showing very reassuring outcomes. Patented inventions along with large trials have shown that prasugrel significantly reduces ischemic end points, ultimately resulting in a decrease in Myocardial infarctions, thromboocculusive episodes and death. Further studies are required to support these findings before we are aware of all clinical effects of Prasugrel.

Topics: Adenosine; Adenosine Monophosphate; Cardiovascular Diseases; Clinical Trials as Topic; Clopidogrel; Humans; Imines; Lactones; Patents as Topic; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2 Receptor Antagonists; Pyridines; Receptor, PAR-1; Receptors, Purinergic P2Y12; Receptors, Thrombin; Thiophenes; Ticagrelor; Ticlopidine

Platelets are major players in arterial thrombosis, and antiplatelet therapy has a clear clinical benefit in the treatment and prevention of cardiovascular events. In particular, aspirin and clopidogrel have become cornerstones in the treatment of patients with atherothrombosis. However, despite the proven efficacy of antiplatelet drugs, cardiovascular events remain an important cause of morbidity and mortality in these patients. Furthermore, a considerable variability in platelet reactivity during treatment with established oral antiplatelet therapy has prompted the search for novel drugs against platelet-dependent thrombosis. Possible benefits of upcoming drugs include a more efficient platelet inhibition and a reversible effect on platelet function. Aspirin, clopidogrel, prasugrel, ticagrelor, terutroban, E5555, SCH 530348 and cilostazol are discussed. This review highlights the rationale for important oral antiplatelet drugs in development and provides clinical perspectives on their pharmacological advantages and challenges.

Topics: Adenosine; Administration, Oral; Cardiovascular Diseases; Cilostazol; Coronary Artery Disease; Coronary Thrombosis; Drug Resistance; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Tetrazoles; Thiophenes; Thromboxane A2; Ticagrelor

Aspirin is the foundation antiplatelet therapy for patients at risk of cardiovascular events. The thienopyridine, clopidogrel, is modestly more effective than aspirin and in patients with stroke seems to be as effective as the combination of aspirin and dipyridamole. The addition of clopidogrel to aspirin further reduces the risk of cardiovascular events in patients with acute coronary syndromes and those who undergo percutaneous coronary intervention, but uncertainty remains about whether this combination has incremental efficacy over clopidogrel monotherapy in patients with stroke or peripheral arterial disease. Clopidogrel has pharmacological limitations that have prompted the search for more effective ADP-receptor antagonists. Promising results have been achieved with the thienopyridine, prasugrel, which has been compared with clopidogrel in patients treated with aspirin. The nonthienopyridine P2Y(12) inhibitors AZD6140 and cangrelor are presently being evaluated in phase III, randomized, controlled trials.

Topics: Adenosine; Adenosine Monophosphate; Angioplasty, Balloon, Coronary; Aspirin; Blood Platelets; Cardiovascular Diseases; Clopidogrel; Drug Therapy, Combination; History, 20th Century; History, 21st Century; Humans; Piperazines; Platelet Aggregation; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2 Receptor Antagonists; Receptors, Purinergic P2; Receptors, Purinergic P2Y12; Stents; Thiophenes; Ticagrelor; Ticlopidine; Treatment Outcome

The evidence for the comparative effectiveness and safety of ticagrelor versus clopidogrel in older patients with acute coronary syndrome (ACS) is limited, especially in the acute phase of ACS. This study aimed to compare the in-hospital outcomes of ticagrelor versus clopidogrel in older patients with ACS.. Hospitalised ACS patients aged ≥75 years who were recruited to the Improving Care for Cardiovascular Disease in China-ACS project between November 2014 and December 2019 and received aspirin and P2Y12 receptor inhibitors within 24 h after first medical contact were included. The primary outcomes were in-hospital major adverse cardiovascular events (MACE) and major bleeding. Multivariable Cox regression was performed to evaluate the comparative effectiveness and safety of ticagrelor and clopidogrel. Inverse probability of treatment weighting (IPTW) and propensity score matching analyses were performed to evaluate the robustness of the results.. Of 18,244 ACS patients, 18.5% received ticagrelor. Multivariable-adjusted analysis revealed comparable risks of in-hospital MACE between patients receiving ticagrelor and clopidogrel (hazard ratio [HR] 1.12, 95% confidence interval [CI] 0.92-1.35). However, ticagrelor use was associated with 45% higher risk of in-hospital major bleeding compared with clopidogrel use (HR 1.45, 95% CI 1.09-1.91). Similar results were found in the IPTW analysis.. ACS patients aged ≥75 years receiving ticagrelor during the acute phase had similar risk of in-hospital MACE, but higher risk of in-hospital major bleeding compared with those receiving clopidogrel. More evidence is needed to guide the use of P2Y12 receptor inhibitors during hospitalisation in older patients with ACS.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02306616.

Topics: Acute Coronary Syndrome; Aged; Cardiovascular Diseases; China; Clopidogrel; Hemorrhage; Hospitals; Humans; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Quality Improvement; Ticagrelor

Background We aimed to evaluate the age-dependent effect of ticagrelor monotherapy after 3-month dual-antiplatelet therapy (DAPT) versus ticagrelor-based 12-month DAPT on major bleeding and cardiovascular events in patients with acute coronary syndrome. Methods and Results From the TICO trial (Ticagrelor Monotherapy After 3 Months in the Patients Treated With New Generation Sirolimus-eluting Stent for Acute Coronary Syndrome), which randomized 3056 patients (median age, 61 years) to the ticagrelor monotherapy after 3-month DAPT group or ticagrelor-based 12-month DAPT group, this post hoc analysis evaluated the age-dependent effect of the treatment strategies on the primary end point (a composite of major bleeding, death, myocardial infarction, stent thrombosis, stroke, or target-vessel revascularization) using the subpopulation treatment effect pattern plot. The cutoff age for distinguishing patients with greater benefit from this strategy was also determined. The risk reduction effect of ticagrelor monotherapy after 3-month DAPT versus ticagrelor-based 12-month DAPT on the primary end point gradually increased with age and was more marked from the subpopulation of age 64 years with the change point. With this cutoff value of 64 years, the occurrence of the primary end point was significantly lower in the ticagrelor monotherapy after 3-month DAPT group than in the ticagrelor-based 12-month DAPT group (4.4% versus 9.0%;

Topics: Acute Coronary Syndrome; Age Distribution; Aged; Aspirin; Cardiovascular Diseases; Drug Therapy, Combination; Hemorrhage; Humans; Middle Aged; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

Rates and predictors of major bleeding in patients with peripheral artery disease (PAD) treated with antiplatelets have not been well studied. This post hoc analysis of EUCLID aimed to determine the incidence of major/minor bleeding, predictors of major bleeding, and risk of major adverse cardiovascular events (MACE) following major bleeding events.. EUCLID, a multicenter randomized controlled trial of 13,885 patients with symptomatic PAD, compared ticagrelor with clopidogrel for the prevention of MACE. The primary safety end point was Thrombolysis in Myocardial Infarction (TIMI) major bleeding. Baseline characteristics were used to develop a multivariable model to determine factors associated with TIMI major bleeding. The occurrence and timing of MACE relative to a first major bleeding event were determined.. TIMI major bleeding occurred in 2.3% of participants overall (0.94 event/100 patient-years). There was no significant difference in major bleeding rates by treatment assignment. Factors associated with TIMI major bleeding included older age, geographic region, Rutherford class, and β-blocker use. Patients with TIMI major bleeding postrandomization had an increased risk of MACE (hazard ratio [HR] 4.46; 95% CI 3.40-5.84; P < .0001) compared with those without major bleeding; the association was strongest within 30 days after a bleeding event.. In patients with symptomatic PAD, 0.94 major bleeding event/100 patient-years was observed and associated with older age, residing in North America, disease severity, and β-blocker use. Patients who had a major bleeding event were significantly more likely to experience MACE, especially within the first 30 days, when compared with patients who did not have major bleeding.

Topics: Adrenergic beta-Antagonists; Age Factors; Aged; Cardiovascular Diseases; Clopidogrel; Double-Blind Method; Female; Hemorrhage; Humans; Incidence; Intention to Treat Analysis; Male; Middle Aged; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Residence Characteristics; Risk Factors; Ticagrelor; Time Factors

After percutaneous coronary intervention (PCI), patients with CYP2C19*2 or *3 loss-of-function (LOF) variants treated with clopidogrel have increased risk of ischemic events. Whether genotype-guided selection of oral P2Y12 inhibitor therapy improves ischemic outcomes is unknown.. To determine the effect of a genotype-guided oral P2Y12 inhibitor strategy on ischemic outcomes in CYP2C19 LOF carriers after PCI.. Open-label randomized clinical trial of 5302 patients undergoing PCI for acute coronary syndromes (ACS) or stable coronary artery disease (CAD). Patients were enrolled at 40 centers in the US, Canada, South Korea, and Mexico from May 2013 through October 2018; final date of follow-up was October 2019.. Patients randomized to the genotype-guided group (n = 2652) underwent point-of-care genotyping. CYP2C19 LOF carriers were prescribed ticagrelor and noncarriers clopidogrel. Patients randomized to the conventional group (n = 2650) were prescribed clopidogrel and underwent genotyping after 12 months.. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia at 12 months. A secondary end point was major or minor bleeding at 12 months. The primary analysis was in patients with CYP2C19 LOF variants, and secondary analysis included all randomized patients. The trial had 85% power to detect a minimum hazard ratio of 0.50.. Among 5302 patients randomized (median age, 62 years; 25% women), 82% had ACS and 18% had stable CAD; 94% completed the trial. Of 1849 with CYP2C19 LOF variants, 764 of 903 (85%) assigned to genotype-guided therapy received ticagrelor, and 932 of 946 (99%) assigned to conventional therapy received clopidogrel. The primary end point occurred in 35 of 903 CYP2C19 LOF carriers (4.0%) in the genotype-guided therapy group and 54 of 946 (5.9%) in the conventional therapy group at 12 months (hazard ratio [HR], 0.66 [95% CI, 0.43-1.02]; P = .06). None of the 11 prespecified secondary end points showed significant differences, including major or minor bleeding in CYP2C19 LOF carriers in the genotype-guided group (1.9%) vs the conventional therapy group (1.6%) at 12 months (HR, 1.22 [95% CI, 0.60-2.51]; P = .58). Among all randomized patients, the primary end point occurred in 113 of 2641 (4.4%) in the genotype-guided group and 135 of 2635 (5.3%) in the conventional group (HR, 0.84 [95% CI, 0.65-1.07]; P = .16).. Among CYP2C19 LOF carriers with ACS and stable CAD undergoing PCI, genotype-guided selection of an oral P2Y12 inhibitor, compared with conventional clopidogrel therapy without point-of-care genotyping, resulted in no statistically significant difference in a composite end point of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia based on the prespecified analysis plan and the treatment effect that the study was powered to detect at 12 months.. ClinicalTrials.gov Identifier: NCT01742117.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Cardiovascular Diseases; Clopidogrel; Coronary Artery Disease; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C19 Inhibitors; Female; Genotype; Genotyping Techniques; Hemorrhage; Heterozygote; Humans; Loss of Function Mutation; Male; Middle Aged; Percutaneous Coronary Intervention; Point-of-Care Testing; Precision Medicine; Purinergic P2Y Receptor Antagonists; Ticagrelor

Background There are limited data on health status instruments in patients with peripheral artery disease and cardiovascular and limb events. We evaluated the relationship between health status changes and cardiovascular and limb events. Methods and Results In an analysis of the EUCLID (Examining Use of Ticagrelor in Symptomatic Peripheral Artery Disease) trial, we examined the characteristics of 13 801 patients by tertile of health status instrument scores collected in the trial (EuroQol 5-Dimensions [EQ-5D], EQ visual analog scale [VAS], and peripheral artery questionnaire). We assessed the association between the baseline health status measurements and major adverse cardiovascular events, major adverse limb events, and lower-extremity revascularization procedures during trial follow-up and the association between 12-month health status change scores and subsequent end points during follow-up. There were 13 217 (95%) patients with EQ-5D scores, 13 533 (98%) with VAS scores, and 4431 (32%) with peripheral artery questionnaire scores. Patients in the lowest baseline EQ-5D tertile (0 to <0.69) were more likely to be female with severe claudication compared with the highest tertile (0.79-1.0;

Topics: Cardiovascular Diseases; Double-Blind Method; Female; Health Status Indicators; Humans; Lower Extremity; Male; Middle Aged; Outcome Assessment, Health Care; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Quality of Life; Surveys and Questionnaires; Symptom Assessment; Ticagrelor; Vascular Surgical Procedures; Visual Analog Scale

Patients with peripheral artery disease have a high risk of future cardiovascular disease events and mortality. Little is known about the changes in symptom classification over time in patients with peripheral artery disease and the association of changes in symptom classification with subsequent cardiovascular disease events.. In this analysis of the EUCLID trial (Examining Use of Ticagrelor in Peripheral Artery Disease), we examined the changes in Rutherford classification (RC) of patients over 12 months. We examined the baseline characteristics of patients by change in symptom classification at 12 months (improved=decreased RC, no change, or worsened=increased RC), and the association between changes in symptom classification (RC) at 12 months and subsequent cardiovascular disease events.. Among 12 759 patients, 3240 (25%) were classified as improved by RC at 12 months, 8132 (64%) as no change, and 1387 (11%) as worsened. At 12 months, many patients who were asymptomatic or had mild/moderate claudication at enrollment had no change in symptom classification over 12 months (73.7% and 70.9%). Patients who worsened over 12 months were more likely to have comorbidities (diabetes mellitus and prior myocardial infarction) and more events (myocardial infarction, amputation, and major bleeding) by 12 months postrandomization, all. Patients with comorbidities and prior history of cardiovascular disease events at baseline and within the first 12 months of the trial were more likely to have worsened symptom classification at 12 months. Worsening symptom classification over 12 months was associated subsequently with an increased risk of all-cause death, amputation, and a composite of cardiovascular death, myocardial infarction, or stroke. Graphic Abstract: A graphic abstract is available for this article.

Topics: Aged; Amputation, Surgical; Cardiovascular Diseases; Clopidogrel; Comorbidity; Disease Progression; Female; Humans; Limb Salvage; Male; Middle Aged; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Prognosis; Risk Assessment; Risk Factors; Symptom Assessment; Ticagrelor; Treatment Outcome

Topics: Adult; Aged; Cardiovascular Diseases; Clopidogrel; Diabetes Complications; Elective Surgical Procedures; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Prospective Studies; Ticagrelor

Objective- The Wnt/wingless signaling antagonist DKK1 (dickkopf-1) regulates platelet-mediated inflammation and may contribute to plaque destabilization. We hypothesized that DKK1 would be associated with cardiovascular outcomes. Approach and Results- We determined DKK1 levels in serum samples obtained before randomization, at discharge, and 1 and 6 months in a subset of 5165 patients with acute coronary syndromes in the PLATO trial (Platelet Inhibition and Patient Outcomes; NCT00391872). The median (interquartile range) DKK1 concentrations were 0.61 (0.20-1.27) ng/mL at baseline and increased during follow-up. The hazard ratio (95% CIs) for the composite end point (cardiovascular death, nonprocedural spontaneous myocardial infarction, or stroke) during 1 year of follow-up, per 50% increase in baseline DKK1 concentration, was 1.06 (1.02-1.10), P=0.0011, and remained significant in fully adjusted analysis with 14 conventional clinical and demographic and 6 biochemical variables, including NT-proBNP (N-terminal pro-B-type natriuretic peptide), hs-TnT (high-sensitivity troponin T), and GDF-15 (growth differentiation factor 15; 1.05 [1.00-1.09]; P=0.028). This association was mainly driven by the association with cardiovascular death, where a gradual increase in event rates was observed with increasing quartiles of DKK1 (2.7%, 3.0%, 4.3%, and 5.0%) and remained significant and unmodified in fully adjusted analysis (hazard ratio, 1.10 [1.04-1.17]; P=0.002). Change in DKK1 and levels at 1 month were unrelated to outcomes. A modifying effect of ticagrelor on DKK1 discharge levels was observed but not associated with prognosis. Conclusions- In patients with acute coronary syndromes treated with dual antiplatelet treatment, admission DKK1 levels were independently associated with a composite of cardiovascular death, myocardial infarction, or stroke and with cardiovascular death alone.

Topics: Acute Coronary Syndrome; Aged; Cardiovascular Diseases; Clopidogrel; Female; Humans; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Ticagrelor

Type-2 Diabetes Mellitus [T2DM] is associated with increased platelet reactivity and hypo-response to antiplatelet drugs. Ticagrelor, with its faster and more potent antiplatelet effects, was shown to reduce adverse events more than clopidogrel in the overall CAD patient population of PLATO trial, but the benefits did not reach statistical significance in the T2DM subgroup. To better understand these findings, we compared the antithrombotic effects of ticagrelor versus with clopidogrel in T2DM patients with cardiovascular disease. In a randomized, 2 treatment-sequence, crossover-design, T2DM patients (n=20, 57±8 years, 60 % male) received a loading-dose [LD] plus one week of daily-therapy [DT] of clopidogrel or ticagrelor. Treatment effects were assessed by measuring thrombus formation (Badimon Chamber) and platelet aggregation (Multiple Electrode Aggregometry (MEA) Analyzer and VerifyNow®) at 2- and 6-hour post-LD and on Day-7 of DT, in comparison with pre-treatment baseline. After 2 weeks of washout, patients switched to the second treatment under identical testing conditions. Ticagrelor significantly reduced thrombus formation versus baseline at 2- and 6-hour post-LD and Day-7 of DT (33 %, 40 % and 31 %, respectively, p<0.01 for all) whereas thrombus reductions with clopidogrel were much lower and significant only at 6-hour post-LD (16 %, 20 % and 17 %, respectively). Antithrombotic effect of ticagrelor at 6-hour was significantly stronger than clopidogrel (p<0.05). Platelet aggregation (MEA and VerifyNow®) was inhibited by both treatments but effects of ticagrelor were significantly stronger at each time-point. Ticagrelor exhibits a faster and more potent antithrombotic effect than clopidogrel in T2DM patients with cardiovascular disease, supporting its use in this population.

Topics: Adenosine; Aged; Blood Platelets; Cardiovascular Diseases; Clopidogrel; Coronary Thrombosis; Cross-Over Studies; Diabetes Mellitus, Type 2; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Platelet Function Tests; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

Peripheral artery disease is considered to be a manifestation of systemic atherosclerosis with associated adverse cardiovascular and limb events. Data from previous trials have suggested that patients receiving clopidogrel monotherapy had a lower risk of cardiovascular events than those receiving aspirin. We wanted to compare clopidogrel with ticagrelor, a potent antiplatelet agent, in patients with peripheral artery disease.. In this double-blind, event-driven trial, we randomly assigned 13,885 patients with symptomatic peripheral artery disease to receive monotherapy with ticagrelor (90 mg twice daily) or clopidogrel (75 mg once daily). Patients were eligible if they had an ankle-brachial index (ABI) of 0.80 or less or had undergone previous revascularization of the lower limbs. The primary efficacy end point was a composite of adjudicated cardiovascular death, myocardial infarction, or ischemic stroke. The primary safety end point was major bleeding. The median follow-up was 30 months.. The median age of the patients was 66 years, and 72% were men; 43% were enrolled on the basis of the ABI and 57% on the basis of previous revascularization. The mean baseline ABI in all patients was 0.71, 76.6% of the patients had claudication, and 4.6% had critical limb ischemia. The primary efficacy end point occurred in 751 of 6930 patients (10.8%) receiving ticagrelor and in 740 of 6955 (10.6%) receiving clopidogrel (hazard ratio, 1.02; 95% confidence interval [CI], 0.92 to 1.13; P=0.65). In each group, acute limb ischemia occurred in 1.7% of the patients (hazard ratio, 1.03; 95% CI, 0.79 to 1.33; P=0.85) and major bleeding in 1.6% (hazard ratio, 1.10; 95% CI, 0.84 to 1.43; P=0.49).. In patients with symptomatic peripheral artery disease, ticagrelor was not shown to be superior to clopidogrel for the reduction of cardiovascular events. Major bleeding occurred at similar rates among the patients in the two trial groups. (Funded by AstraZeneca; EUCLID ClinicalTrials.gov number, NCT01732822 .).

Topics: Adenosine; Aged; Cardiovascular Diseases; Clopidogrel; Double-Blind Method; Female; Hemorrhage; Humans; Intermittent Claudication; Ischemia; Kaplan-Meier Estimate; Leg; Male; Middle Aged; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine

Ticagrelor reduced cardiovascular events compared with clopidogrel in PLATO without increasing overall major bleeding. We evaluated whether the use of glycoprotein IIb/IIIa inhibitor (GPI) impacts the relative efficacy and safety of ticagrelor compared with clopidogrel.. PLATO randomized 18,624 subjects with acute coronary syndrome to ticagrelor versus clopidogrel. The primary efficacy end point was cardiovascular death/myocardial infarction/stroke, and the primary safety end point was major bleeding. The use of GPI was at the physician's discretion and open-label. We evaluated outcomes at 30 days stratified by GPI use in the subgroup of 9,983 patients who underwent percutaneous coronary intervention (PCI) within 72 hours.. A total of 4,020 (40%) received a GPI. Those receiving a GPI were more likely to be younger, be male, and undergo multivessel PCI. There was no interaction between treatment and GPI use for the primary efficacy and safety end points. Patients treated without GPI had a lower rate of definite stent thrombosis and higher rate of minor/major bleeding with ticagrelor compared with clopidogrel (P < .05), whereas there was no such difference with GPI (P interaction < .05).. In patients with acute coronary syndrome undergoing early PCI, the efficacy and safety of ticagrelor as compared with clopidogrel were not modified by GPI use according to the primary efficacy and safety end point of the trial, although there were indications of greater benefit on definite stent thrombosis and more major or minor bleeding with ticagrelor in patients without (vs with) GPI treatment.

Topics: Abciximab; Acute Coronary Syndrome; Adenosine; Aged; Antibodies, Monoclonal; Aspirin; Cardiovascular Diseases; Clopidogrel; Drug Therapy, Combination; Drug-Eluting Stents; Eptifibatide; Female; Graft Occlusion, Vascular; Hemorrhage; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Myocardial Infarction; Peptides; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Purinergic P2Y Receptor Antagonists; Stroke; Thrombosis; Ticagrelor; Ticlopidine; Tirofiban; Tyrosine

For patients with coronary artery disease undergoing coronary bypass surgery, acetylsalicylic acid (ASA) currently represents the gold standard of antiplatelet treatment. However, adverse cardiovascular event rates in the first year after coronary artery bypass grafting (CABG) still exceed 10%. Graft failure, which is predominantly mediated by platelet aggregation, has been identified as a major contributing factor in this context. Therefore, intensified platelet inhibition is likely to be beneficial. Ticagrelor, an oral, reversibly binding and direct-acting P2Y12 receptor antagonist, provides a rapid, competent, and consistent platelet inhibition and has shown beneficial results compared with clopidogrel in the subset of patients undergoing bypass surgery in a large previous trial.. Ticagrelor is superior to ASA for the prevention of major cardiovascular events within 1 year after CABG.. The TiCAB trial (NCT01755520) is a multicenter, phase III, double-blind, double-dummy, randomized trial comparing ticagrelor with ASA for the prevention of major cardiovascular events within 12 months after CABG. Patients undergoing CABG will be randomized in a 1:1 fashion to either ticagrelor 90 mg twice daily or ASA 100 mg once daily. The study medication will be started within 24 hours after surgery and maintained for 12 months. The primary end point is the composite of cardiovascular death, myocardial infarction, stroke, and repeat revascularization at 12 months after CABG. The sample size is based on an expected event rate of 13% of the primary end point within the first 12 months after randomization in the control group, a 2-sided α level of .0492 (to preserve the overall significance level of .05 after planned interim analysis), a power of 0.80%, 2-sided testing, and an expected relative risk of 0.775 in the active group compared with the control group and a dropout rate of 2%. According to power calculations based on a superiority design for ticagrelor, it is estimated that 3,850 patients should be enrolled.. There is clinical equipoise on the issue of optimal platelet inhibition after CABG. The TiCAB trial will provide a pivotal comparison of the efficacy and safety of ticagrelor compared with ASA after CABG.

Topics: Adenosine; Aged; Aspirin; Cardiovascular Diseases; Coronary Artery Bypass; Coronary Artery Disease; Double-Blind Method; Female; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Stroke; Ticagrelor; Treatment Outcome

The potential benefit of dual antiplatelet therapy beyond 1 year after a myocardial infarction has not been established. We investigated the efficacy and safety of ticagrelor, a P2Y12 receptor antagonist with established efficacy after an acute coronary syndrome, in this context.. We randomly assigned, in a double-blind 1:1:1 fashion, 21,162 patients who had had a myocardial infarction 1 to 3 years earlier to ticagrelor at a dose of 90 mg twice daily, ticagrelor at a dose of 60 mg twice daily, or placebo. All the patients were to receive low-dose aspirin and were followed for a median of 33 months. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The primary safety end point was Thrombolysis in Myocardial Infarction (TIMI) major bleeding.. The two ticagrelor doses each reduced, as compared with placebo, the rate of the primary efficacy end point, with Kaplan-Meier rates at 3 years of 7.85% in the group that received 90 mg of ticagrelor twice daily, 7.77% in the group that received 60 mg of ticagrelor twice daily, and 9.04% in the placebo group (hazard ratio for 90 mg of ticagrelor vs. placebo, 0.85; 95% confidence interval [CI], 0.75 to 0.96; P=0.008; hazard ratio for 60 mg of ticagrelor vs. placebo, 0.84; 95% CI, 0.74 to 0.95; P=0.004). Rates of TIMI major bleeding were higher with ticagrelor (2.60% with 90 mg and 2.30% with 60 mg) than with placebo (1.06%) (P<0.001 for each dose vs. placebo); the rates of intracranial hemorrhage or fatal bleeding in the three groups were 0.63%, 0.71%, and 0.60%, respectively.. In patients with a myocardial infarction more than 1 year previously, treatment with ticagrelor significantly reduced the risk of cardiovascular death, myocardial infarction, or stroke and increased the risk of major bleeding. (Funded by AstraZeneca; PEGASUS-TIMI 54 ClinicalTrials.gov number, NCT01225562.).

Topics: Adenosine; Aged; Aspirin; Cardiovascular Diseases; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Hemorrhage; Humans; Intracranial Hemorrhages; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Risk; Secondary Prevention; Ticagrelor

We evaluated whether electrocardiogram (ECG) characteristics were aligned with clinical outcomes and the effect of ticagrelor within the diverse spectrum of non-ST-elevation acute coronary syndrome patients enrolled in the PLATelet inhibition and patient Outcomes (PLATO) trial.. There were 8884 PLATO patients who had baseline ECGs assessed by a core laboratory; of these, 4935 had an ECG at hospital discharge that also was assessed. Associations with study treatment on vascular death or myocardial infarction within 1 year were examined.. At baseline, most patients had either no or ≤0.5 mm of ST-segment depression (57%); 26% had 1.0 mm, and 17% had more extensive depression (>1.0 mm). Across the baseline ST-segment depression strata, there was a consistent treatment benefit with ticagrelor versus clopidogrel on vascular death/myocardial infarction. The extent of residual ST-segment depression at discharge was similar in the treatment groups, and the treatment effect did not differ by the extent of discharge ST-segment depression. There was a progressive increase in vascular death/myocardial infarction with increasing extent of baseline ST-segment depression (1.0 mm [vs no/0.5 mm]: hazard ratio [HR] 1.22; 95% confidence interval [CI], 1.03-1.45; >1.0 mm: HR 1.49; 95% CI, 1.24-1.78; P <.001) and at discharge (HR 1.28; 95% CI, 1.02-1.61; HR 2.13; 95% CI, 1.54-2.95; P <.001).. The treatment effect of ticagrelor among non-ST-segment-elevation acute coronary syndrome patients was consistently expressed across all baseline ST-segment depression strata. There was no indication of an anti-ischemic benefit of ticagrelor as reflected on the discharge ECG. Our data affirm the independent prognostic relationship of both baseline and hospital discharge ST-segment depression on outcomes within 1 year in non-ST-segment-elevation acute coronary syndrome patients.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Cardiovascular Diseases; Clopidogrel; Cohort Studies; Electrocardiography; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Prognosis; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

Elderly patients with acute coronary syndrome are at high risk of recurrent ischemic events and death, and for both antithrombotic therapy and catheter-based complications. This prespecified analysis investigates the effect and treatment-related complications of ticagrelor versus clopidogrel in elderly patients (≥75 years of age) with acute coronary syndrome compared with those <75 years of age.. The association between age and the primary composite outcome, as well as major bleeding were evaluated in the PLATelet inhibition and patient Outcomes (PLATO) trial using Cox proportional hazards. Similar models were used to evaluate the interaction of age with treatment effects. Hazard ratios were adjusted for baseline characteristics. The clinical benefit of ticagrelor over clopidogrel was not significantly different between patients aged ≥75 years of age (n=2878) and those <75 years of age (n=15 744) with respect to the composite of cardiovascular death, myocardial infarction, or stroke (interaction P=0.56), myocardial infarction (P=0.33), cardiovascular death (P=0.47), definite stent thrombosis (P=0.81), or all-cause mortality (P=0.76). No increase in PLATO-defined overall major bleeding with ticagrelor versus clopidogrel was observed in patients aged ≥75 years (hazard ratio, 1.02; 95% confidence interval, 0.82-1.27) or patients aged <75 years (hazard ratio, 1.04; 95% confidence interval, 0.94-1.15). Dyspnea and ventricular pauses were more common during ticagrelor than clopidogrel treatment, with no evidence of an age-by-treatment interaction.. The significant clinical benefit and overall safety of ticagrelor compared with clopidogrel in acute coronary syndrome patients in the PLATO cohort were not found to depend on age.

Topics: Acute Coronary Syndrome; Adenosine; Age Factors; Aged; Cardiovascular Diseases; Chi-Square Distribution; Clopidogrel; Double-Blind Method; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Patient Safety; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Stents; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

Reduced renal function is associated with a poorer prognosis and increased bleeding risk in patients with acute coronary syndromes and may therefore alter the risk-benefit ratio with antiplatelet therapies. In the Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor compared with clopidogrel reduced the primary composite end point of cardiovascular death, myocardial infarction, and stroke at 12 months but with similar major bleeding rates.. Central laboratory serum creatinine levels were available in 15 202 (81.9%) acute coronary syndrome patients at baseline, and creatinine clearance, estimated by the Cockcroft Gault equation, was calculated. In patients with chronic kidney disease (creatinine clearance <60 mL/min; n=3237), ticagrelor versus clopidogrel significantly reduced the primary end point to 17.3% from 22.0% (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.65 to 0.90) with an absolute risk reduction greater than that of patients with normal renal function (n=11 965): 7.9% versus 8.9% (HR, 0.90; 95% CI, 0.79 to 1.02). In patients with chronic kidney disease, ticagrelor reduced total mortality (10.0% versus 14.0%; HR, 0.72; 95% CI, 0.58 to 0.89). Major bleeding rates, fatal bleedings, and non-coronary bypass-related major bleedings were not significantly different between the 2 randomized groups (15.1% versus 14.3%; HR, 1.07; 95% CI, 0.88 to 1.30; 0.34% versus 0.77%; HR, 0.48; 95% CI, 0.15 to 1.54; and 8.5% versus 7.3%; HR, 1.28; 95% CI, 0.97 to 1.68). The interactions between creatinine clearance and randomized treatment on any of the outcome variables were nonsignificant.. In acute coronary syndrome patients with chronic kidney disease, ticagrelor compared with clopidogrel significantly reduces ischemic end points and mortality without a significant increase in major bleeding but with numerically more non-procedure-related bleeding.. URL:http://www.clinicatrials.gov. Unique identifier: NCT00391872.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Cardiovascular Diseases; Chronic Disease; Clopidogrel; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Kidney Diseases; Male; Middle Aged; Outcome Assessment, Health Care; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Antagonists; Receptors, Purinergic P2Y12; Risk Factors; Ticagrelor; Ticlopidine; Treatment Outcome

Cardiovascular disease (CVD) is often associated with asthma, and asthma patients have an increased risk of CVD mortality. Our understanding of the bidirectional risk of CVD and asthma has been based on several observational studies. However, specific pathogenetic mechanisms underlying the development of cardiovascular comorbidities in patients with asthma have not yet been fully determined. Such cardiovascular complications in patients with asthma have been attributed to airway and systemic inflammation present in both asthma and CVD. Indeed, there is evidence that mast cells, eosinophils, inflammatory cytokines, and immunoglobulin E increase in both lungs of patients with asthma and in injured heart and vessels of CVD patients. These findings suggest that allergic asthma and CVD may share pathogenic pathways. Understanding these pathways is critical to the choice of pharmacological interventions. Currently, the most appropriate therapeutic approach lies in using the best available evidence to optimize the management of both asthma and CVD. Therapy should be optimized to take advantage of the favorable benefits that each medication may have on both organs while minimizing the likelihood of adverse effects on the lungs and heart. It is noteworthy that inhaled β2-agonists provide benefits in patients with acute decompensated heart failure. Furthermore, inhaled corticosteroids may reduce the risk of atherosclerosis. On the other hand, asthma is not an absolute contraindication to using cardio-selective β1-blockers, but these medications should be prescribed with caution, especially if they are necessary to prevent acute cardiovascular events, and alternative treatment options are unavailable. In addition, when aspirin intake causes the onset of hypersensitivity, P2Y12 inhibitors (e.g., clopidogrel, prasugrel, and ticagrelor) are effective and safe treatment alternatives.

Topics: Asthma; Cardiovascular Diseases; Clopidogrel; Comorbidity; Humans; Ticagrelor

The POPular Risk Score (PRiS), a pharmacogenetic-driven algorithm consisting of CYP2C19 genotype, platelet reactivity, and clinical risk factors, is developed to evaluate ischemic risk and guide dual antiplatelet therapy (DAPT). This study aimed to evaluate the efficacy and safety of DAPT in accordance with the PRiS in patients undergoing drug-eluting stent (DES) implantation.. A total of 1757 patients recruited in this cohort study were divided into four groups according to the PRiS and type of P2Y12 receptor inhibitor treatment at discharge. The primary endpoint was major adverse cardiovascular events (MACE, a composite of cardiovascular death, myocardial infarction, stroke, definite or probable stent thrombosis, and target vessel revascularization) during 1-year follow-up. The safety endpoints were defined by Bleeding Academic Research Consortium (BARC) criteria as major bleeding (BARC 3a, 3b, 3c, and 5) and clinically relevant bleeding (BARC 2, 3a, 3b, 3c, and 5).. Among 1046 patients with PRiS < 2 and 711 patients with PRiS ≥ 2, 34.2% and 38.3% of them were treated with ticagrelor, respectively. The PRiS ≥ 2 was an independent predictor for the 1-year incidence of MACE (HR(95%CI): 2.09 (1.37-3.20), p = 0.001). Multivariable Cox regression indicated that in the PRiS ≥ 2 group, ticagrelor was superior to clopidogrel in reducing the risk of MACE (HR(95%CI): 0.53 (0.29-0.98), p = 0.042), without increasing the bleeding risk. On the other hand, in the PRiS < 2 group, clopidogrel treatment was related to a remarkably lower rate of BARC class ≥ 2 bleeding (HR(95%CI): 0.39 (0.20-0.72), p = 0.003), but comparable incidences of MACE and BARC class ≥ 3 bleeding during 1-year follow-up. Similar associations between P2Y12 receptor inhibitors and 1-year endpoints in the PRiS < 2 and PRiS ≥ 2 group could also be identified in propensity score-weighted analysis and propensity score-matched analysis.. Tailored DAPT based on the PRiS could assist in improving the prognosis of patients undergoing DES implantation. Further randomized controlled trials are required to provide more evidence for PRiS-guided DAPT.

Topics: Aged; Algorithms; Asian People; Aspirin; Cardiovascular Diseases; China; Clopidogrel; Comorbidity; Cytochrome P-450 CYP2C19; Drug-Eluting Stents; Dual Anti-Platelet Therapy; Female; Health Behavior; Hemorrhage; Humans; Male; Middle Aged; Pharmacogenetics; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Risk Assessment; Risk Factors; Sociodemographic Factors; Ticagrelor; Ticlopidine

Previous studies have shown that ticagrelor reduced risk of pneumonia in patients with acute coronary syndrome (ACS) compared to clopidogrel, however, its effect in patients with non-ACS cardiovascular diseases remains uncertain. The aim was to investigate the effect of ticagrelor on pneumonia and pneumonia-specific death compared to clopidogrel in non-ACS patients in Hong Kong. This was a population-based cohort study. We included consecutive patients using ticagrelor or clopidogrel admitted for non-ACS conditions in Hong Kong public hospitals from March 2012 to September 2019. Patients using both drugs were excluded. The outcomes of interest were incident pneumonia, all-cause death, and pneumonia-specific death. Multivariable survival analysis models were used to estimate the effects [hazard ratio (HR) and 95% confidence interval (CI)]. Propensity score matching, adjustment and weighting were performed as sensitivity analyses. In total, 90,154 patients were included (mean age 70.66 years, males 61.7%). The majority of them (97.2%) used clopidogrel. Ticagrelor was associated with a lower risk of incident pneumonia [0.59 (0.46-0.75)], all-cause death [0.83 (0.73-0.93)] and pneumonia-specific death [0.49 (0.36-0.67)]. Sensitivity analyses yielded similar results. Ticagrelor was associated with lower risk of all-cause death, pneumonia-specific death, and incident pneumonia in patients with non-ACS cardiovascular conditions, consistent with previous evidence in patients with ACS. This additional effect of anti-pneumonia should be considered when choosing a proper P2Y12 inhibitor for patients with high risk of pneumonia.

Topics: Aged; Cardiovascular Diseases; Cause of Death; Clopidogrel; Cohort Studies; Female; Hong Kong; Hospitals, Public; Humans; Male; Platelet Aggregation Inhibitors; Pneumonia; Propensity Score; Retrospective Studies; Ticagrelor

Topics: Cardiovascular Diseases; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Female; Humans; Male; Randomized Controlled Trials as Topic; Ticagrelor; Treatment Outcome

To investigate the long-term clinical benefit of dual antiplatelet therapy with potent P2Y12 inhibitors compared to clopidogrel in patients with acute coronary syndrome (ACS).. In this prospective multicenter observational study, we enrolled 708 patients with ACS treated with clopidogrel (n = 137), ticagrelor (n = 260) or prasugrel (n = 311). Major adverse cardiac events (MACE; over 1 year) and long-term mortality (median: 5.6 years; interquartile range [IQR] 4.9-6.5 years) were assessed. Multiple electrode aggregometry (MEA) was used to measure adenosine diphosphate (ADP)- and arachidonic acid (AA)-induced platelet aggregation.. Type of P2Y12 inhibitor emerged as an independent predictor of long-term mortality and MACE: patients treated with potent platelet inhibitors prasugrel or ticagrelor were at lower risk for long-term mortality (adjusted hazard ratio [HR] = 0.44; 95% CI: 0.22-0.92; P = .028) or MACE (adjusted HR = 0.38; 95% CI: 0.20-0.73; P = .004) than those treated with clopidogrel independent from clinical risk factors. In contrast, the efficacy of clopidogrel decreased with increasing severity of ACS: platelet aggregation was 37% higher in patients with ST segment elevation myocardial infarction (STEMI) and 25% higher in patients with non-ST elevation myocardial infarction (non-STEMI) compared to patients with unstable angina (P = .039). Patients with diabetes achieved less potent ADP- and AA-induced platelet inhibition under clopidogrel, compared to patients without diabetes (P = .045; P = .030, respectively).. In the setting of ACS, treatment with ticagrelor or prasugrel reduced long-term mortality and 1-year MACE as compared to clopidogrel.

Topics: Acute Coronary Syndrome; Adenosine Diphosphate; Aged; Arachidonic Acid; Aspirin; Cardiovascular Diseases; Clopidogrel; Dual Anti-Platelet Therapy; Female; Humans; Male; Middle Aged; Mortality; Myocardial Infarction; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Prognosis; Proportional Hazards Models; Prospective Studies; Secondary Prevention; Stroke; Survival Rate; Ticagrelor

Background Peripheral artery disease (PAD) is a known risk factor for adverse outcomes in patients undergoing percutaneous coronary intervention. However, in some studies PAD is not an independent risk factor. We sought to examine the independent impact of PAD on a large prospective percutaneous coronary intervention registry. Methods and Results From our single-center prospective percutaneous coronary intervention registry, we have retrospectively analyzed 25 690 patients (years 2004-2018). We examined the influence of PAD on short- and long-term outcomes using both regression and propensity-matched analyses. Patients with documented PAD (n=1610, 6.3% of total) were older (66.7±10.8 versus 65.4±12.1,

Topics: Aged; Cardiovascular Diseases; Cause of Death; Diabetes Mellitus; Female; Humans; Hypertension; Male; Middle Aged; Percutaneous Coronary Intervention; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Registries; Renal Insufficiency; Retrospective Studies; Risk Factors; Ticagrelor; Treatment Outcome

Ischemic and bleeding events portend equivalently poor prognosis after percutaneous coronary intervention (PCI). Risk factors for these untoward events largely overlap limiting the "decoupling" of bleeding and ischemic risk. While individual patient risk scores inform the duration of guideline recommended dual antiplatelet therapy (DAPT) to strike the optimal balance between ischemic and bleeding risk, a promising additional approach is to tailor the regimens themselves. In higher risk patients, 1 month of aspirin plus ticagrelor followed by 23 months of ticagrelor monotherapy has equivalent bleeding and numerically improved ischemic risk than standard DAPT for 12 months followed by aspirin monotherapy in the GLOBAL LEADERS trial. In the TWILIGHT study of high ischemic and bleeding risk patients, 12 months of ticagrelor monotherapy had lower bleeding risk with equivalent ischemic risk as DAPT after 3 months of successful DAPT. Individual risk scores should be developed informing both optimal antiplatelet regimen such as ticagrelor monotherapy and treatment duration after PCI.

Topics: Cardiovascular Diseases; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; tau Proteins; Ticagrelor; Treatment Outcome

Trends and clinical factors associated with prescribing choices for oral P2Y12 inhibitors (P2Y12-I) remain unknown for patients on chronic dialysis, i.e., with end-stage renal disease (ESRD).. From 2011-2014 U.S. Renal Data System registry, we identified 36,542 ESRD patients who received new prescriptions for P2Y12-I (median age 64.0 years and 54% males). Of the cohort, 93% were receiving hemodialysis and 7% on peritoneal dialysis. We analyzed trends and investigated clinical factors associated with specific P2Y12-I prescribed.. Clopidogrel was prescribed for 95%, prasugrel for 3%, and ticagrelor for 2%. Clopidogrel was favored for those ≥75 years (18% of cohort). Compared to Caucasians, African Americans (36% of cohort) and Hispanics (19% of cohort) were less likely to receive prasugrel and ticagrelor (P<0.05). Patients receiving hemodialysis versus peritoneal dialysis were less likely to receive prasugrel over clopidogrel, adjusted odds ratio (aOR) 0.67 (0.55-0.82). Each additional year of dialysis decreased the odds of receiving prasugrel over clopidogrel, aOR 0.91 (0.85-0.98). History of atrial fibrillation reduced the odds of receiving ticagrelor or prasugrel over clopidogrel, aOR 0.69 (0.54-0.89) and 0.73 (0.60-0.89), respectively. Concomitant oral anticoagulant use was not associated with choice of P2Y12-I. Occurrence of non-ST segment elevation myocardial infarction or percutaneous coronary intervention within the 6-month period prior to the index date favored ticagrelor over prasugrel, aOR 1.31 (1.06-1.62) and 1.29 (1.01-1.66), respectively. However, prescribing trends favoring ticagrelor over prasugrel were not observed for deployment of drug-eluting, or multiple coronary stents.. Between 2011 and 2014, clopidogrel remained the most common P2Y12-I whereas ticagrelor and prasugrel remained underutilized in ESRD patients. Prescribing practices for these drugs were based upon clinically approved indication for their use in the general population as well as perceived complexity of an ESRD patient including demographics, dialysis-related factors and comorbidities. Comparative effectiveness studies involving ESRD patients are needed to prove that ticagrelor and prasugrel are just as safe and effective as clopidogrel before clinicians can make informed decisions for choice of P2Y12-I in this patient population.

Topics: Administration, Oral; Adolescent; Adult; Aged; Cardiovascular Diseases; Clinical Decision-Making; Clopidogrel; Drug Prescriptions; Drug Utilization; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Patient Selection; Peritoneal Dialysis; Platelet Aggregation Inhibitors; Practice Patterns, Physicians'; Prasugrel Hydrochloride; Prevalence; Purinergic P2Y Receptor Antagonists; Registries; Renal Dialysis; Retrospective Studies; Risk Assessment; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome; United States; Young Adult

Topics: Cardiovascular Diseases; Eicosapentaenoic Acid; Humans; Hypertriglyceridemia; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Risk Factors; Ticagrelor

Despite great advances with the introduction of ticagrelor and prasugrel in the treatment of acute coronary syndromes (ACS), the risk of thrombosis and bleeding remains significant and affects the choice of clinicians in the treatment of the single patient. Large registries are effective tools to explore patterns of drug administration and adherence to guideline recommendations in real-world clinical practice.. START- antiplatelet is a prospective, observational registry carried out by seven Italian cardiology institutions on patients admitted for ACS aimed to document the real world treatment of ACS patients, adding also data on 12-month follow-up. We present data on the first 1050 patients who have completed 1-year follow-up on a total of 1537 patients. Primary end-points were: 1) MACCE (Major Adverse Cardiovascular and Cerebrovascular Events) including all-cause and cardiovascular mortality, non fatal MI, urgent revascularization, TIA and ischemic stroke; 2) Major and minor bleeding according to TIMI, GUSTO and ISTH classifications.. The dual antiplatelet treatment most prescribed was aspirin plus ticagrelor (47.9%) and aspirin plus clopidogrel (32.1%). At a mean follow-up was 335±131 days, both ticagrelor and prasugrel are associated with a statistically significant reduced total and cardiovascular mortality. Both prasugrel and ticagrelor do not show a significant increased incidence of major and minor bleedings with respect to clopidogrel. Patients with monotherapy had significantly higher incidence of both ischemic stroke and major bleedings.. The analysis of the register has documented that both ticagrelor and prasugrel are associated with a statistically significant reduced total and cardiovascular mortality but both do not show a significant increased incidence of major and minor bleedings with respect to clopidogrel.

Topics: Acute Coronary Syndrome; Aged; Cardiovascular Diseases; Cerebrovascular Disorders; Female; Follow-Up Studies; Hemorrhage; Humans; Italy; Kaplan-Meier Estimate; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Registries; Risk; Stroke; Thrombosis; Ticagrelor; Treatment Outcome

Background Prior reports indicate that the effect of P2Y

Topics: Acute Coronary Syndrome; Aged; Angina, Unstable; Asian People; Cardiovascular Diseases; Cause of Death; Clopidogrel; Female; Hemorrhage; Humans; Male; Middle Aged; Mortality; Myocardial Infarction; Prasugrel Hydrochloride; Proportional Hazards Models; Purinergic P2Y Receptor Antagonists; Recurrence; Republic of Korea; Stroke; Ticagrelor; Treatment Outcome

There are few data on ticagrelor in Asian patients. This study evaluated clinical outcomes with ticagrelor and clopidogrel in Taiwanese patients with acute myocardial infarction (AMI).Methods and Results:We used the Taiwan National Health Insurance Research Database to identify 27,339 AMI patients aged ≥18 years between January 2012 and December 2014, and only patients who survived greater than or equal to 30 days after AMI and took dual antiplatelet therapy were included. Cohorts of ticagrelor and clopidogrel were matched 1:8, based on propensity score matching, to balance baseline covariates. The primary efficacy endpoints were death from any cause, AMI, or stroke. The safety endpoints consisted of major gastrointestinal bleeding or intracerebral hemorrhage. Following propensity matching, the primary efficacy endpoint rate was 22% lower in the ticagrelor group than in the clopidogrel group (10.6% and 16.2%, respectively; adjusted HR, 0.779; 95% CI: 0.684-0.887). The safety endpoint rate was similar between the ticagrelor and clopidogrel groups (3.2% and 4.1% respectively; adjusted HR, 0.731; 95% CI: 0.522-1.026).. In real-world AMI Taiwanese patients, ticagrelor seemed to offer better anti-ischemic protection than clopidogrel, without an increase in the rate of major bleeding. A large-scale randomized trial is needed to assess the efficacy and safety of ticagrelor in East Asian AMI patients.

Topics: Aged; Asian People; Cardiovascular Diseases; Clopidogrel; Hemorrhage; Humans; Ischemia; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Propensity Score; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Risk; Taiwan; Ticagrelor; Treatment Outcome

Topics: Adverse Drug Reaction Reporting Systems; Cardiovascular Diseases; Clopidogrel; Humans; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor; United States; United States Food and Drug Administration

Topics: Adverse Drug Reaction Reporting Systems; Aged; Cardiovascular Diseases; Comorbidity; Data Accuracy; Diabetes Mellitus; Female; Humans; Male; Prasugrel Hydrochloride; Research Design; Risk Assessment; Risk Factors; Ticagrelor; Treatment Outcome; United States; United States Food and Drug Administration

There is little information regarding comparison of ticagrelor and prasugrel in patients with ST-segment elevation myocardial infarction (STEMI). We sought to compare clinical outcomes between ticagrelor and prasugrel in STEMI.Methods and Results:A total of 1,440 patients with STEMI who underwent successful primary percutaneous coronary intervention were analyzed; the data were obtained from the Korea Acute Myocardial Infarction Registry-National Institutes of Health. Of the patients, 963 received ticagrelor, and 477 received prasugrel. The primary study endpoint was 12-month major adverse cardiac events (MACE), including cardiac death, myocardial infarction (MI), and target vessel revascularization (TVR). MACE occurred in 91 patients (6.3%) over the 1-year follow-up, and there were no differences in the incidence of MACE (hazard ratio [HR] 1.20, 95% confidence interval [CI] 0.76-1.91, P=0.438) between the 2 groups. Analysis by propensity score matching (429 pairs) did not significantly affect the results. The incidence of in-hospital major bleeding events was still comparable between the 2 groups (2.4% vs. 2.5%, odds ratio 0.75, 95% CI 0.30-1.86, P=0.532), and there was no significant difference in the incidence of MACE (5.4% vs. 5.8%, HR 0.98, 95% CI 0.56-1.74, P=0.951) after matching.. Ticagrelor and prasugrel showed similar efficacy and safety profiles for treating STEMI in this Korean multicenter registry.

Topics: Aged; Cardiovascular Diseases; Cohort Studies; Female; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Registries; Republic of Korea; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

Atherosclerosis is being thought of as an autoimmune disease. As the most potent antigen-presenting cells, dendritic cells (DCs) have been regarded as a major target for the control of this harmful immune response. In this study, we investigated the effect of ticagrelor, a new antiplatelet drug antagonizing the P2Y12 receptor, on the function of mouse bone marrow-derived DCs. RT-PCR revealed relatively high P2Y12 mRNA levels in DCs, and expression of the P2Y12 protein was documented by western blot analysis. Moreover, antigen (Ag) uptake by DCs was markedly increased following activation of the P2Y12 receptor by adenosine-5'-O-(2-thiodiphosphate) (ADPβS). Ticagrelor reduced the ADPβS-stimulated uptake of fluorescein-labeled dextran by DCs while exerting no significant effect on spontaneous endocytosis. In addition, ticagrelor suppressed the capacity of ADPβS-stimulated DCs to induce activation of T lymphocytes. Ticagrelor blocked the activation of phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated kinase 1/2 (ERK1/2) in ADPβS-treated DCs. Preventing the activation of PI3K reduced significantly ADPβS-induced endocytosis by DCs. Thus, ticagrelor decreases Ag uptake by DCs via the inhibition of P2Y12 receptor-mediated PI3K activity, attenuating the stimulation of Ag-specific T cells. Our findings indicate that ticagrelor may directly target DCs and inhibit their function, suggesting a possible explanation for the immunoregulatory activity of this drug.

Topics: Animals; Cardiovascular Diseases; Dendritic Cells; Mice; Phosphatidylinositol 3-Kinases; Platelet Aggregation Inhibitors; Ticagrelor

Topics: Cardiovascular Diseases; Clopidogrel; Endothelium, Vascular; Humans; Purinergic P2Y Receptor Antagonists; Ticagrelor; Vasodilation

The reasons for postdischarge adenosine diphosphate receptor inhibitor (ADPri) switching among patients with myocardial infarction (MI) are unclear. We sought to describe the incidence and patterns of postdischarge ADPri switching among patients with acute MI treated with percutaneous coronary intervention.. We used TRANSLATE-ACS (2010-2012) data to assess postdischarge ADPri switching among 8,672 MI patients discharged after percutaneous coronary intervention who remained on ADPri therapy 1 year post-MI. We examined patient-reported reasons for switching, GUSTO moderate or severe bleeding, major adverse cardiovascular events (MACEs), and definite stent thrombosis events around the time of the switch.. Among patients still on ADPri therapy 1 year post-MI, 663 (7.6%) switched ADPri during that year. Switching occurred at a median of 50 days postdischarge and most frequently in patients discharged on ticagrelor (64/226; 28.3%), followed by prasugrel (383/2,489; 15.4%) and clopidogrel (216/5,957; 3.6%) (P < .001). Among patients discharged on prasugrel, 97.3% of switches were to clopidogrel and 87.5% of ticagrelor switches were to clopidogrel; both of these groups most often cited cost as a reason for switching (43.6% and 39.1%, respectively), whereas 60.7% who switched from clopidogrel cited physician decision as a reason. In the 7 days preceding the switch from clopidogrel, 40 (18.5%) had a MACE and 12 (5.6%) had a definite stent thrombosis event, whereas that from prasugrel or ticagrelor, a GUSTO moderate or severe bleeding event occurred in 1 (0.3%) and 0 patients, respectively.. Postdischarge ADPri switching occurred infrequently within the first year post-MI and uncommonly was associated with MACEs or bleeding events.

Topics: Adenosine; Adenosine Diphosphate; Aged; Cardiovascular Diseases; Clopidogrel; Drug Substitution; Female; Hemorrhage; Humans; Longitudinal Studies; Male; Middle Aged; Myocardial Infarction; Patient Discharge; Patient Preference; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P1 Receptor Antagonists; Ticagrelor; Ticlopidine

Topics: Adenosine; Adverse Drug Reaction Reporting Systems; Cardiovascular Diseases; Clinical Trials as Topic; Drug-Related Side Effects and Adverse Reactions; Humans; Purinergic P2Y Receptor Antagonists; Ticagrelor; United States; United States Food and Drug Administration

Vorapaxar, a novel antiplatelet thrombin PAR-1 inhibitor, has been evaluated in TRA2P and TRACER trials. The drug is currently approved for post-myocardial infarction and peripheral artery disease indications with concomitant use of clopidogrel and/or aspirin. The FDA ruled that the overall vorapaxar data quality was acceptable, but conducted the sensitivity analyses for potential censoring. This was unusual, intriguing, and directly related to the challenged quality of ticagrelor dataset in PLATO in the previous New Drug Application for an oral antiplatelet agent submitted to the same Agency.. Hence, we compared the FDA-confirmed evidence of conduct and data quality in vorapaxar (TRA2P, and TRACER) with those of ticagrelor (PLATO) trials.. The FDA provides a detailed report on information censoring, and follow-up completeness for 3 trials. TRA2P and TRACER used independent CRO for site monitoring, exhibit no heterogeneity in trial results dependent on geography, and consistent adjudication results with much less censoring than in PLATO.. The data quality and trial conduct in vorapaxar trials were better than testing ticagrelor in PLATO, however, there is still some room for improvement especially with regard to follow-up completeness, and less information censoring.

Topics: Adenosine; Cardiovascular Diseases; Data Accuracy; Humans; Lactones; Multicenter Studies as Topic; Pyridines; Randomized Controlled Trials as Topic; Receptor, PAR-1; Ticagrelor; United States; United States Food and Drug Administration

Despite dual antiplatelet treatment, major ischemic events are common following ST elevation myocardial infarction (STEMI). We aimed to assess high platelet reactivity on aspirin (HPR-aspirin) and its association with P2Y12i (HPR-P2Y12i) during the acute phase of STEMI.. We included all consecutive patients admitted for STEMI treated by primary angioplasty in our center for 1year. All patients received a loading dose followed by a maintenance dose of aspirin (75mg/day) and prasugrel (ticagrelor or clopidogrel if contraindicated). Platelet reactivity was assessed 4±1days and 75±15days after admission using light transmission aggregometry with arachidonic acid (LTA-AA-HPR-aspirin) and VASP (HPR-P2Y12i) to define HPR as well as serum Thromboxane-B2 and LTA-ADP. Major cardiac and cerebrovascular events were recorded for 1year.. We included 106 patients - mean age was 61y.o., 76% were male and 20% had diabetes. STEMI was anterior in 52% and LV ejection fraction at discharge was 51±9%. 50% of patients were treated with prasugrel and 34% with ticagrelor. At day 4 after STEMI, HPR-aspirin was found in 26% patients and HPR-P2Y12i in 7%. HPR- both aspirin and P2Y12i was found in 4%. Diabetes and age were predictors of HPR-aspirin. HPR-aspirin was persistent 75days later in 36% patients. At 1year, 7.9% patients had experienced major adverse cardiovascular and cerebrovascular events (MACCE). HPR-aspirin and HPR on both aspirin and P2Y12i were significantly associated with MACCE.. HPR-aspirin is frequent just after STEMI and associated with MACCE especially when associated with HPR-P2Y12i.

Topics: Acute Disease; Adenosine; Aspirin; Blood Platelets; Brain Ischemia; Cardiovascular Diseases; Clopidogrel; Female; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Survival Analysis; Ticagrelor; Ticlopidine

 To estimate the potential magnitude in unselected patients of the benefits and harms of prolonged dual antiplatelet therapy after acute myocardial infarction seen in selected patients with high risk characteristics in trials..  Observational population based cohort study..  PEGASUS-TIMI-54 trial population and CALIBER (ClinicAl research using LInked Bespoke studies and Electronic health Records)..  7238 patients who survived a year or more after acute myocardial infarction..  Prolonged dual antiplatelet therapy after acute myocardial infarction..  Recurrent acute myocardial infarction, stroke, or fatal cardiovascular disease. Fatal, severe, or intracranial bleeding..  1676/7238 (23.1%) patients met trial inclusion and exclusion criteria ("target" population). Compared with the placebo arm in the trial population, in the target population the median age was 12 years higher, there were more women (48.6% v 24.3%), and there was a substantially higher cumulative three year risk of both the primary (benefit) trial endpoint of recurrent acute myocardial infarction, stroke, or fatal cardiovascular disease (18.8% (95% confidence interval 16.3% to 21.8%) v 9.04%) and the primary (harm) endpoint of fatal, severe, or intracranial bleeding (3.0% (2.0% to 4.4%) v 1.26% (TIMI major bleeding)). Application of intention to treat relative risks from the trial (ticagrelor 60 mg daily arm) to CALIBER's target population showed an estimated 101 (95% confidence interval 87 to 117) ischaemic events prevented per 10 000 treated per year and an estimated 75 (50 to 110) excess fatal, severe, or intracranial bleeds caused per 10 000 patients treated per year. Generalisation from CALIBER's target subgroup to all 7238 real world patients who were stable at least one year after acute myocardial infarction showed similar three year risks of ischaemic events (17.2%, 16.0% to 18.5%), with an estimated 92 (86 to 99) events prevented per 10 000 patients treated per year, and similar three year risks of bleeding events (2.3%, 1.8% to 2.9%), with an estimated 58 (45 to 73) events caused per 10 000 patients treated per year..  This novel use of primary-secondary care linked electronic health records allows characterisation of "healthy trial participant" effects and confirms the potential absolute benefits and harms of dual antiplatelet therapy in representative patients a year or more after acute myocardial infarction.

Topics: Adenosine; Aged; Aged, 80 and over; Aspirin; Cardiovascular Diseases; Cause of Death; Clinical Trials as Topic; Cohort Studies; Coronary Disease; Drug Therapy, Combination; Electronic Health Records; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Risk Factors; Secondary Prevention; Stroke; Ticagrelor; Time Factors

The platelet inhibitor ticagrelor is strongly recommended during 12 months post-acute coronary syndrome (ACS) in European guidelines. We analysed clinical characteristics of patients given ticagrelor for ACS in the real world.. We studied the use of ticagrelor in patients admitted for ACS in Sweden between 1 January 2012 and 31 December 2013 who were enrolled in the Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART). Clinical characteristics were investigated for patients prescribed ticagrelor at discharge as well as for patients undergoing percutaneous coronary intervention who were prescribed ticagrelor. Independent factors associated with selecting ticagrelor were analysed in logistic regression. We found that 44.0% (n = 12 601) out of a total of 28 639 patients had been prescribed ticagrelor at discharge. After adjusting for age and sex, prior cardiovascular disease was less common in patients discharged on ticagrelor (myocardial infarction, ischaemic stroke, and peripheral vascular disease; P for all <0.001). The risk of death as predicted by GRACE score and the risk of major bleeding as predicted by CRUSADE score were both lower in ticagrelor-treated patients vs. others (median 99 vs. 126 and median 23 vs. 25, respectively; P for both < 0.001). The intended treatment duration at discharge was 12 months in 82.5% of patients and <12 months in 9.3%.. Ticagrelor is preferentially being used in patients at lower risk. A minority of patients are recommended ticagrelor during <12 months.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Aged, 80 and over; Cardiovascular Diseases; Coronary Thrombosis; Databases, Factual; Evidence-Based Medicine; Female; Guideline Adherence; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Postoperative Complications; Postoperative Hemorrhage; Purinergic P2Y Receptor Antagonists; Risk Assessment; Sweden; Ticagrelor

In the cardiovascular area, the rate of occurrence of relevant clinical events decreased over the last decades due to the large adoption of evidence-based treatments. This implies that large numbers of patients are needed to provide reliable answers to research open questions. Therefore, the conduction of multinational large-scale studies became necessary. In this setting, it is not infrequent to find relevant differences in the trial results across countries. The interpretation of these differences should be extremely cautious to avoid the well known mistakes related to subgroup analyses. To believe in differences, it is necessary to adopt appropriate methodologies in the analysis of data but, even more important, to find a biological plausibility that can explain the observed difference. A further confirmation from other studies can also help in the interpretation. In the literature there are some examples of such differences that, in some cases, produced erroneous interpretations of the results of a trial, and also induced regulatory authorities to take decisions based on these differences.

Topics: Acute Coronary Syndrome; Adenosine; Americas; Benzazepines; Cardiovascular Agents; Cardiovascular Diseases; Clinical Trials as Topic; Clopidogrel; Ethnicity; Europe; Female; Georgia (Republic); Heart Failure; Humans; Internationality; Male; Metoprolol; Multicenter Studies as Topic; Platelet Aggregation Inhibitors; Russia; Sample Size; Spironolactone; Ticagrelor; Ticlopidine; Tolvaptan

Topics: Adenosine; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Cardiovascular Diseases; Clopidogrel; Dabigatran; Fibrinolytic Agents; Guideline Adherence; Humans; Morpholines; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Thromboembolism; Ticagrelor; Ticlopidine; Treatment Outcome

To compare hemorrhagic events between clopidogrel and ticagrelor in the Platelet Inhibition and Patient Outcomes (PLATO) trial.. We examined the FDA Medical Review.. Compared to clopidogrel, ticagrelor significantly increased spontaneous bleeds, major bleeds, major plus minor bleeds, and major plus minor plus minimal bleeds. Ticagrelor also increased both major and fatal/life-threatening bleeds versus clopidogrel when CABG was performed between 24 and 96 h after stopping medication, which was also accompanied by a larger volume of chest tube drainage and transfusions. Moreover, ticagrelor increased CABG-related bleeding versus clopidogrel in those patients who did not wait until day 5 after stopping treatment to have CABG. Additionally, compared to clopidogrel, ticagrelor increased the risk of hematuria (RR=1.91; 95% CI: 0.95-3.83), intracranial hemorrhage or subdural or other hematoma (RR 1.87; 95% CI: 1.02-3.42), subcutaneous hemorrhage, ecchymosis, hematoma (RR=1.63; 95% CI: 0.84-3.17), epistaxis (RR=1.49; 95% CI: 0.67-3.32), retroperitoneal hematoma or hemorrhage (RR=1.49; 95% CI: 0.53-4.19), gastrointestinal/anal bleed (RR=1.23; 95% CI: 0.93-1.64) and bleed/hematoma (RR=1.21, 95% CI: 1.02-1.43).. Clopidogrel is safer than ticagrelor in regard to bleeding. Additionally, ticagrelor's purported faster antiplatelet 'offset' is substantially longer than its pharmacokinetics indicate. Considering the fact that the mortality, stent thrombosis and myocardial infarction 'benefit' of ticagrelor have recently been challenged, and that the increase in stroke on ticagrelor has recently been shown to be worse than originally published, the decision to use ticagrelor over clopidogrel in the face of a higher risk for bleeds is not advised.

Topics: Adenosine; Cardiovascular Diseases; Clopidogrel; Dose-Response Relationship, Drug; Hemorrhage; Humans; Incidence; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine

Topics: Adenosine; Cardiovascular Diseases; Clopidogrel; Humans; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine; United States; United States Food and Drug Administration

Topics: Adenosine; Cardiovascular Diseases; Clopidogrel; Humans; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Thiophenes; Ticagrelor; Ticlopidine

Central adjudication in randomised controlled outcome-driven trials represents a traditional approach to maintain data integrity by applying uniformed rules for assessment of clinical events. It was the purpose of this investigation to determine the patterns of myocardial infarction (MI) adjudication in the TRITON, RECORD, and PLATO trials. We were matching centrally-adjudicated MI's (CAMI's) from the official trial publication with the site-reported MI (SRMI's) count from the Food and Drug Administration's secondary analyses for the investigational compounds prasugrel (TRITON), rosiglitazone (RECORD), and ticagrelor (PLATO). CAMI numbers showed a remarkable discrepancy to SRMI's by more than a doubling of the difference: from 72 to 145 events in TRITON favoring prasugrel (from a hazard ratio [HR]=0.76, p=0.08; to a HR=0.76, p<0.001), and from 44 to 89 events in favour of ticagrelor in PLATO (from a HR=0.94, p=0.095; to a HR=0.84, p<0.001). In contrast, in the RECORD trial, the CAMI count was less than the SRMI count (from 24 to 8 events, from a HR=1.42, p=0.93; to a HR=1.14, p=0.96), in this case diminishing cardiovascular hazards in favour of rosiglitazone. In conclusion, central adjudication in the TRITON, the RECORD, and the PLATO trial turned out to have a critical impact on study outcomes. Trial publications should in the future include site-reported major efficacy and safety endpoints to preserve data integrity. The regulatory authorities should consider independent audits when there is a major disagreement between centrally adjudicated and site reported events influencing the results of a major clinical trial.

Topics: Acute Coronary Syndrome; Adenosine; Cardiovascular Diseases; Clinical Trials, Phase III as Topic; Combined Modality Therapy; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Judgment; Metformin; Multicenter Studies as Topic; Myocardial Infarction; Observer Variation; Outcome Assessment, Health Care; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Process Assessment, Health Care; Randomized Controlled Trials as Topic; Rosiglitazone; Stroke; Sulfonylurea Compounds; Thiazolidinediones; Thiophenes; Ticagrelor

Despite the inclusion of investigator-industry pecuniary and non-pecuniary associations in published clinical trials, the benefit of such disclosures may be limited. Two recent pivotal phase III drug studies that raised conflict of interest issues are discussed. It is recommended that in the future, a firewall should be erected between industry and investigators.

Topics: Adenosine; Cardiovascular Diseases; Clinical Trials as Topic; Clinical Trials Data Monitoring Committees; Clinical Trials, Phase III as Topic; Conflict of Interest; Drug Industry; Early Termination of Clinical Trials; Fluorobenzenes; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Meta-Analysis as Topic; Motivation; Multicenter Studies as Topic; Periodicals as Topic; Platelet Aggregation Inhibitors; Pyrimidines; Reproducibility of Results; Research Support as Topic; Rosuvastatin Calcium; Sulfonamides; Ticagrelor; Truth Disclosure

Topics: Adenosine; Aged; Aged, 80 and over; Cardiovascular Diseases; Clinical Trials as Topic; Female; Humans; Male; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome

The FDA has approved ticagrelor (Brilinta-AstraZeneca), an oral antiplatelet drug, for use with low-dose aspirin to reduce the rate of thrombotic cardiovascular events in patients with acute coronary syndrome (ACS). It will compete with clopidogrel (Plavix) and prasugrel (Effient) for such use. Clopidogrel is expected to become available generically in the US within the next few months.

Topics: Adenosine; Aspirin; Cardiovascular Diseases; Clopidogrel; Drug Approval; Drug Interactions; Drug Therapy, Combination; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Thiophenes; Ticagrelor; Ticlopidine; United States

In the PLATO trial of ticagrelor versus clopidogrel for treatment of acute coronary syndromes, ticagrelor reduced the composite outcome of cardiovascular death, myocardial infarction, and stroke, but increased events of major bleeding related to non-coronary artery bypass graft (CABG). CYP2C19 and ABCB1 genotypes are known to influence the effects of clopidogrel. In this substudy, we investigated the effects of these genotypes on outcomes between and within treatment groups.. DNA samples obtained from patients in the PLATO trial were genotyped for CYP2C19 loss-of-function alleles (*2, *3, *4, *5, *6, *7, and *8), the CYP2C19 gain-of-function allele *17, and the ABCB1 single nucleotide polymorphism 3435C→T. For the CYP2C19 genotype, patients were stratified by the presence or absence of any loss-of-function allele, and for the ABCB1 genotype, patients were stratified by predicted gene expression (high, intermediate, or low). The primary efficacy endpoint was the composite of cardiovascular death, myocardial infarction, or stroke after up to 12 months' treatment with ticagrelor or clopidogrel.. 10 285 patients provided samples for genetic analysis. The primary outcome occurred less often with ticagrelor versus clopidogrel, irrespective of CYP2C19 genotype: 8·6% versus 11·2% (hazard ratio 0·77, 95% CI 0·60-0·99, p=0·0380) in patients with any loss-of-function allele; and 8·8% versus 10·0% (0·86, 0·74-1·01, p=0·0608) in those without any loss-of-function allele (interaction p=0·46). For the ABCB1 genotype, event rates for the primary outcome were also consistently lower in the ticagrelor than in the clopidogrel group for all genotype groups (interaction p=0·39; 8·8%vs 11·9%; 0·71, 0·55-0·92 for the high-expression genotype). In the clopidogrel group, the event rate at 30 days was higher in patients with than in those without any loss-of-function CYP2C19 alleles (5·7%vs 3·8%, p=0·028), leading to earlier separation of event rates between treatment groups in patients with loss-of-function alleles. Patients on clopidogrel who had any gain-of-function CYP2C19 allele had a higher frequency of major bleeding (11·9%) than did those without any gain-of-function or loss-of-function alleles (9·5%; p=0·022), but interaction between treatment and genotype groups was not significant for any type of major bleeding.. Ticagrelor is a more efficacious treatment for acute coronary syndromes than is clopidogrel, irrespective of CYP2C19 and ABCB1 polymorphisms. Use of ticagrelor instead of clopidogrel eliminates the need for presently recommended genetic testing before dual antiplatelet treatment.. AstraZeneca.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Aryl Hydrocarbon Hydroxylases; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cardiovascular Diseases; Clopidogrel; Cytochrome P-450 CYP2C19; Female; Genotype; Humans; Male; Pharmacogenetics; Phenotype; Platelet Aggregation Inhibitors; Polymorphism, Single Nucleotide; Randomized Controlled Trials as Topic; Ticagrelor; Ticlopidine

Topics: Acute Coronary Syndrome; Adenosine; Cardiovascular Diseases; Chronic Disease; Hemorrhage; Humans; Kidney Diseases; Purinergic P2 Receptor Antagonists; Receptors, Purinergic P2Y12; Risk Factors; Ticagrelor

Topics: Acute Coronary Syndrome; Adenosine; Cardiovascular Diseases; Clopidogrel; Humans; Multicenter Studies as Topic; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Ticagrelor; Ticlopidine

Topics: Adenosine; Adenosine Diphosphate; Cardiovascular Diseases; Humans; Platelet Activation; Platelet Aggregation Inhibitors; Ticagrelor