ticagrelor and Coronary-Thrombosis

More potent antithrombotic strategies have significantly reduced the rate of recurrent ischemic events in cardiovascular disease. Ticagrelor, in particular, has significantly improved the outcome in patients with acute coronary syndromes, offering potential benefits also in terms of survival. In addition, more recent data have suggested that the advantages of ticagrelor could be extended also to non-coronary atherothrombotic disease, although with contrasting results, especially for mortality reduction. The aim of the present meta-analysis was to investigate the safety and effectiveness of a newer antiplatelet strategy with ticagrelor as compared to traditional antiplatelet regimens in patients with coronary or non-coronary atherothrombotic disease.. Literature and main scientific session abstracts were searched for studies comparing a ticagrelor-based antiplatelet regimen vs. different antiplatelet agents in the secondary prevention of cardiac, cerebral or vascular atherothrombotic events. The primary efficacy endpoint was mortality, primary safety endpoint was the occurrence of major bleedings. Secondary endpoints were myocardial infarction and stroke.. We included 10 randomized clinical trials, for a total population of 73,121 patients, 54.9% randomized to ticagrelor. At a mean follow-up of 13.4 ± 12.6 months, a newer antiplatelet strategy based on ticagrelor was associated with a significant reduction in mortality as compared to a traditional therapy (OR[95%CI] = 0.92[0.86,0.99], p=0.02; phet = 0.14), however, such benefits were more evident in patients with coronary artery disease, while not in non-coronary trials, with a significant interaction between patients' setting and the prognostic impact of ticagrelor (p int = 0.03). A similar result was achieved for cardiovascular mortality, recurrent myocardial infarction, while for the risk of stroke, the largest advantages were observed in patients with a previous cerebrovascular accident. Major bleeding events were increased in ticagrelor treated patients (OR [95%CI] = 1.11 [1.02, 1.20], p=0.01; phet = 0.0003), although not affecting overall mortality, as confirmed by meta-regression analysis.. Based on the current meta-analysis, a newer antiplatelet strategy based on ticagrelor is associated with a significant reduction in mortality and recurrent cardiovascular events, as compared to a traditional treatment, among patients treated for coronary disease but not among those with non-coronary atherothrombotic disease. However, ticagrelor therapy was associated with a significant increase in major bleeding complications.

Topics: Atherosclerosis; Coronary Artery Disease; Coronary Thrombosis; Humans; Randomized Controlled Trials as Topic; Thrombosis; Ticagrelor

Stent thrombosis is a morbid complication following percutaneous coronary intervention (PCI). Dual antiplatelet therapy significantly reduces stent thrombosis risk. However, the antiplatelet response to clopidogrel - the most frequently used ADP receptor antagonist in post-PCI patients - varies among individuals. High on-treatment platelet reactivity was repeatedly associated with the risk of stent thrombosis. Ticagrelor is a novel ADP receptor blocker that has shown greater, more rapid and more consistent platelet inhibition than clopidogrel. This agent offers a unique mechanism of action, no relevant pharmacological interactions, consistent platelet inhibition, and a good safety profile. This article reviews the prospective use of ticagrelor in the treatment of stent thrombosis in acute coronary syndrome patients undergoing PCI of culprit coronary lesion.

Topics: Acute Coronary Syndrome; Adenosine; Angioplasty, Balloon, Coronary; Blood Platelets; Clopidogrel; Coronary Thrombosis; Drug Resistance; Humans; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2; Stents; Ticagrelor; Ticlopidine

The study sought to compare the clinical efficacy and safety of P2Y12 inhibitors in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous intervention (PPCI).. Limited data exist regarding the comparative efficacy and safety of P2Y12 inhibitors in STEMI patients undergoing PPCI.. Clinical trials enrolling STEMI patients were identified and relevant data was extracted. Major adverse cardiovascular events (MACE) were defined as the composite of all cause mortality, MI, and target vessel revascularization. Network meta-analysis was performed using Bayesian methods.. A total of 37 studies with 88,402 STEMI patients and 5,077 MACE were analyzed. Outcomes at 1 month (22 studies and 60,783 patients) suggest that prasugrel was associated with: lower MACE than clopidogrel (standard dose odds ratio [OR]: 0.59, 95% confidence interval [CI]: 0.50 to 0.69; high-dose OR: 0.60, 95% CI: 0.51 to 0.71; upstream OR: 0.79, 95% CI: 0.66 to 0.94), and ticagrelor (standard dose OR: 0.69, 95% CI: 0.56 to 0.84; upstream OR: 0.72, 95% CI: 0.50 to 1.05); lower mortality and MI than clopidogrel and standard ticagrelor; lower stroke risk than standard clopidogrel and standard or upstream ticagrelor; and lower stent thrombosis than standard or upstream clopidogrel. At 1-year (10 studies, n = 40,333) prasugrel was associated with lower mortality and MACE than other P2Y12 inhibitors. MACE was particularly lower with prasugrel in studies where patients received bivalirudin, drug-eluting stents, and but not glycoprotein IIb/IIIa inhibitor.. In STEMI patients undergoing PPCI, prasugrel and ticagrelor are more efficacious than clopidogrel; in addition, prasugrel was superior to ticagrelor particularly in conjunction with bivalirudin and drug-eluting stents.

Topics: Adenosine; Antithrombins; Bayes Theorem; Blood Platelets; Clinical Trials as Topic; Clopidogrel; Coronary Thrombosis; Drug-Eluting Stents; Evidence-Based Medicine; Hirudins; Humans; Markov Chains; Monte Carlo Method; Network Meta-Analysis; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Recombinant Proteins; Risk Factors; ST Elevation Myocardial Infarction; Ticagrelor; Ticlopidine; Treatment Outcome

Effective antagonism of the P2Y12 platelet receptor is central to the treatment of acute coronary syndrome (ACS) patients, especially in the setting of percutaneous coronary intervention and stenting. According to consensus guidelines, early revascularization and intensive antiplatelet therapy are key to reducing the complications that arise from myocardial ischaemia and the recurrence of cardiovascular events. Until recently, clopidogrel was the key P2Y12 antagonist advocated, but due to several limitations as an antiplatelet agent, newer drugs with more predictable, rapid and potent effects have been developed. Prasugrel and ticagrelor are now the recommended first-line agents in patients presenting with non-ST-segment elevation ACS and ST-segment elevation ACS, due to large-scale randomized trials that demonstrated net clinical benefit of these agents over clopidogrel, as stated in the European guidelines. Although no study has directly compared the two agents, analysis of the data to date suggests that certain patient types, such as diabetics, those with ST-segment elevation myocardial infarction or renal failure and the elderly may have a better outcome with one agent over the other. Further studies are needed to confirm these differences and answer pending questions regarding the use of these drugs to optimize efficacy while minimizing adverse events, such as bleeding. The aim of this review is to provide an overview of the current P2Y12 receptor antagonists in the treatment of ACS, with a focus on issues of appropriate agent selection, timing of treatment, bleeding risk and the future role of personalized treatment using platelet function and genetic testing.

Topics: Acute Coronary Syndrome; Adenosine; Adenosine Monophosphate; Clinical Trials as Topic; Clopidogrel; Combined Modality Therapy; Coronary Artery Bypass; Coronary Thrombosis; Diabetes Complications; Hemorrhage; Humans; Multicenter Studies as Topic; Piperazines; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prasugrel Hydrochloride; Precision Medicine; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Receptors, Purinergic P2Y12; Renal Insufficiency; Thiophenes; Ticagrelor; Ticlopidine; Treatment Outcome

Despite the improvement in stent technology, stent thrombosis (ST), a potentially catastrophic event, still occurs. Among several risk factors for ST, high on-treatment platelet reactivity to clopidogrel has been demonstrated to play a role, occurring in about one-third of the patients. In order to overcome this limitation, prasugrel and ticagrelor, newer P2Y12 inhibitors, have been developed and approved for clinical use. Two large clinical trials, TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet inhibitioN with prasugrel-thrombolysis in myocardial infarction (TRITON-TIMI) 38 and Study of Platelet Inhibition and Patient Outcomes (PLATO), evaluated these drugs in patients with acute coronary syndrome (ACS), showing a significant improvement in efficacy end points (including a prominent reduction in ST occurrence) compared to clopidogrel. In contrast, the TRILOGY ACS trial found no benefit with prasugrel compared to clopidogrel in patients with medically treated ACS. The aim of this review is to consider decision-making strategies between prasugrel and ticagrelor in daily clinical practice.

Topics: Acute Coronary Syndrome; Adenosine; Coronary Thrombosis; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Stents; Thiophenes; Ticagrelor

Dual antiplatelet therapy with aspirin plus a P2Y(12) receptor inhibitor is the cornerstone of treatment for patients with acute coronary syndrome and in those undergoing percutaneous coronary intervention. Clopidogrel is the most widely used P2Y(12) receptor inhibitor. Despite the clinical benefits associated with adjunctive clopidogrel therapy, a considerable number of patients continue to experience recurrent cardiovascular events. Importantly, the interindividual response to clopidogrel is variable and is affected by multiple factors, including genetic polymorphisms and drugs that interfere with the conversion of clopidogrel to its active metabolite. The individual variability to clopidogrel-induced antiplatelet effects has significant clinical implications that can result in an increased risk of atherothrombotic recurrences, including stent thrombosis. The introduction of novel P2Y(12) receptor inhibitors, such as prasugrel or ticagrelor, characterized by more potent and consistent platelet inhibitory effects, represents an opportunity for clinicians to consider these alternative therapies to overcome the limitations of clopidogrel. Understanding the strategies and implications of switching antiplatelet treatment regimens is, therefore, key in the clinical setting. This article provides an overview of the literature on switching antiplatelet treatment strategies and practical considerations for the interventional cardiologist.

Topics: Acute Coronary Syndrome; Adenosine; Aspirin; Clopidogrel; Coronary Thrombosis; Drug Interactions; Drug Substitution; Drug Therapy, Combination; Humans; Percutaneous Coronary Intervention; Pharmacogenetics; Piperazines; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

Clopidogrel and ticagrelor, antagonists to P2Y(12) receptor molecules on platelet membranes, significantly ameliorate acute myocardial infarction due to coronary artery thrombosis, the most common cause of death in the developed world. A personal account is given here of the foundational research that lead to the identification of P2Y receptors, carried out 50 years ago in the Melbourne University Zoology Department headed by Geoffrey Burnstock. In Christmas 1962, I made the serendipitous observation of large hyperpolarizing changes across the membranes of smooth muscle cells in the taenia coli of the intestine on stimulating its nerve supply. I then showed that these potentials relaxed the muscle and were not due to noradrenaline or acetylcholine, which were then the only substances known to be released from nerves. I called these non-adrenergic, non-cholinergic (NANC) terminals in the laboratory and showed that this NANC transmitter acted at receptor molecules on the muscle cells, promoting efflux of potassium ions, and so the observed potential changes. In 1968, Graeme Campbell showed that ATP relaxed the taenia coli muscle, and in 1969, David Satchell, using purine chromatography, showed that ATP was likely to be released from NANC terminals. The receptor molecules involved were shown to be exceptionally sensitive to 2-methylthio-ATP (Satchell and Macguire, 1975, J Pharmacol Exp Ther, 195, 540), and so belonged to the class P2Y receptors as designated by Abbracchio and Burnstock, with subclasses P2Y(1)-P2Y(12). The discovery of the role of P2Y(12) receptors in increasing thrombosis lead to the focused research that resulted in clopidogrel and ticagrelor.

Topics: Adenosine; Animals; Clopidogrel; Coronary Artery Disease; Coronary Thrombosis; History, 20th Century; Humans; Muscle, Smooth; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y; Ticagrelor; Ticlopidine

Administration of a P2Y 12 -receptor antagonist in addition to aspirin is mandatory in patients with acute coronary syndromes (ACS) or undergoing percutaneous coronary intervention (PCI) to reduce the occurrence of thrombotic events; however, their impact on mortality and stroke is unclear. We aimed to evaluate the influence of moderate (clopidogrel) or potent (prasugrel/ticagrelor) P2Y 12 -receptor inhibition on major cardiovascular outcomes among patients with ACS or undergoing PCI. Systematic literature search was performed to find randomised, controlled clinical trials comparing the clinical impact of clopidogrel with placebo or prasugrel/ticagrelor versus clopidogrel. Outcome measures included cardiovascular death, myocardial infarction (MI), total stroke and intracranial haemorrhage (ICH). Random-effects model with Mantel-Heanszel weighting was used to pool outcomes into a meta-analysis. Four studies comparing clopidogrel with placebo and five trials comparing clopidogrel with new P2Y 12 -receptor inhibitors were identified including a total of 107,473 patients. Compared to placebo, clopidogrel reduced the risk of cardiovascular death (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.87-0.99, p=0.02), MI (OR 0.80; 95%CI 0.74-0.88, p<0.00001) and stroke (OR 0.84; 95%CI 0.72-0.97, p=0.02), without influencing risk for ICH (OR 0.96; 95%CI 0.69-1.33, p=0.79). Treatment with prasugrel/ticagrelor provided additional benefit over clopidogrel regarding cardiovascular mortality (OR 0.86; 95%CI 0.78-0.94, p=0.002) and MI (OR: 0.83; 95%CI 0.74-0.93, p<0.001), but no advantage in stroke (OR: 1.06; 95%CI 0.88-1.26, p=0.55) and in ICH (OR: 1.16; 95%CI 0.75-1.81; p=0.49) was observed. Increased potency of P2Y 12 -receptor inhibition is associated with decreased risk in cardiovascular death and MI; however, this association is not true in case of stroke, where potent P2Y 12 -receptor antagonists have no incremental benefit over clopidogrel.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Clopidogrel; Coronary Thrombosis; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Risk Assessment; Risk Factors; Stroke; Thiophenes; Ticagrelor; Ticlopidine; Treatment Outcome

P2Y12 adenosine di-phosphate (ADP) receptor antagonists are critical to reduce thrombotic recurrences in acute coronary syndromes patients and for those undergoing percutaneous coronary revascularization. Multiple lines of evidence suggest that the level of on-treatment platelet reactivity inhibition with P2Y12 ADP receptor antagonists correlates with thrombotic recurrences. Recent studies observed a relationship between excessive platelet reactivity inhibition and bleedings. Together these data support the potential of platelet reactivity measurement to prevent thrombotic events without increasing bleeding. In the present review we aimed to summarize evidences of a therapeutic window for P2Y12-ADP receptor antagonists and the potential of platelet reactivity monitoring and individualized antiplatelet therapy to optimize the clinical outcome in patients suffering from an acute coronary syndrome or undergoing percutaneous coronary intervention.

Topics: Acute Coronary Syndrome; Adenosine; Aspirin; Blood Platelets; Clopidogrel; Coronary Thrombosis; Drug Interactions; Drug Resistance; Genotype; Hemorrhage; Humans; Patient Selection; Percutaneous Coronary Intervention; Pharmacogenetics; Phenotype; Piperazines; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Precision Medicine; Predictive Value of Tests; Receptors, Purinergic P2Y12; Risk Assessment; Risk Factors; Thiophenes; Ticagrelor; Ticlopidine; Treatment Outcome

Inhibiting platelet function is a key therapeutic principle in cardiology because platelets play a pivotal role in triggering cardiovascular events. In addition to acetylsalicylic acid, a cyclooxygenase inhibitor, ADP-receptor blockers are frequently used for anti-platelet therapy. This therapy does not abolish platelet activation and aggregation. Platelets may still be activated by alternative routes such as the thrombin receptor-mediated pathway. New, more potent inhibitors of platelet function continue to lower the risk of ischaemic events but several trials and clinical registries have also shown that this advantage was frequently offset by an increased risk of bleeding complications. As a consequence, the individual risk of ischaemia and bleeding of a patient must be taken into consideration to select the platelet inhibitor offering the best benefit-risk ratio. Modern laboratory diagnostics may help to achieve this goal by complementing functional platelet tests with pharmacogenomic analyses consistent with the idea of "personalized medicine".

Topics: Acute Coronary Syndrome; Adenosine; Adenosine Monophosphate; Aspirin; Clopidogrel; Coronary Thrombosis; Drug Interactions; Hemorrhage; Humans; Piperazines; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticagrelor; Ticlopidine

Antithrombotic agents are the cornerstones of therapy for thrombosis. The compositions of arterial and venous clots differ, rendering antiplatelet agents more effective for arterial thrombosis and anticoagulants more effective for venous disease. Despite taking acetylsalicylic acid, some patients with arterial disease experience thrombotic events. The addition of the ADP-receptor antagonist clopidogrel to therapeutic regimens containing acetylsalicylic acid improves outcomes in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention. However, clopidogrel has several limitations, including variable absorption, drug-drug interactions and genetic factors that lead to reduced generation of the active metabolite, and a delayed onset and offset of action. A search for new ADP-receptor inhibitors has yielded drugs such as prasugrel, ticagrelor, and cangrelor. For patients with venous thrombosis, the coumarins have been the only available oral anticoagulants for more than 60 years. Despite their effectiveness in preventing and treating thromboembolism, coumarins have well-documented limitations, including drug-drug and drug-dietary interactions, a narrow therapeutic range, and inconvenience and cost of monitoring therapy. A search for new oral anticoagulants has yielded drugs such as dabigatran etexilate, rivaroxaban, and apixaban. In this article, we review these new antithrombotic agents and provide plausible explanations for the results of phase III randomized controlled trials of these drugs.

Topics: Adenosine; Anticoagulants; Aspirin; Clopidogrel; Coronary Thrombosis; Coumarins; Fibrinolytic Agents; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Thiophenes; Thromboembolism; 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

Platelets possess three P2 receptors for adenine nucleotides: P2Y1 and P2Y12, which interact with ADP, and P2X1, which interacts with ATP. The interaction of adenine nucleotides with their platelet receptors plays an important role in thrombogenesis. The thienopyridine ticlopidine, an antagonist of the platelet P2Y12 ADP receptor, reduces the incidence of vascular events in patients at risk, but it also has some important drawbacks: a relatively high incidence of toxic effects; delayed onset of action; high inter-individual variability in response. Another thienopyridine, clopidogrel, has superseded ticlopidine, because it is an efficacious antithrombotic drug and is less toxic than ticlopidine. However, the high inter-patient variability in response still remains an important issue. These drawbacks justify the continuing search for agents that can further improve the clinical outcome of patients with atherosclerosis through greater efficacy and/or safety. A new thienopyridyl compound prasugrel, which is characterized by higher potency and faster onset of action compared with clopidogrel, is currently under clinical evaluation. Two direct and reversible P2Y12 antagonists, cangrelor and AZD6140, have very rapid onset and reversal of platelet inhibition, which make them attractive alternatives to thienopyridines, especially when rapid inhibition of platelet aggregation or its quick reversal are required. Along with new P2Y12 antagonists, inhibitors of the other platelet receptor for ADP, P2Y1, and of the receptor for ATP, P2X1, are under development and may prove to be effective antithrombotic agents.

Topics: Adenosine; Adenosine Monophosphate; Angina, Unstable; Animals; Blood Platelets; Clopidogrel; Coronary Disease; Coronary Thrombosis; Drug Interactions; Fibrinolytic Agents; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2 Receptor Antagonists; Randomized Controlled Trials as Topic; Receptors, Purinergic P2; Receptors, Purinergic P2X; Syndrome; Thiophenes; Ticagrelor; Ticlopidine

Topics: Acute Coronary Syndrome; Aged; Angina, Unstable; Coronary Angiography; Coronary Thrombosis; Early Medical Intervention; Female; Humans; Male; Middle Aged; Non-ST Elevated Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Time Factors; Tomography, Optical Coherence; Treatment Outcome

This study assessed the ability of the dual-antiplatelet therapy (DAPT) score in stratifying ischemic and bleeding risk in a contemporary percutaneous coronary intervention (PCI) population.. The DAPT score is recommended by guidelines as a tool to stratify ischemic and bleeding risk. Its utility in contemporary PCI is unknown.. The study studied patients in GLOBAL LEADERS (A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation) who were free of major ischemic and bleeding events and adhered to antiplatelet strategy during the first year after PCI. The primary ischemic endpoint was the composite of myocardial infarction or stent thrombosis. The primary bleeding endpoint was Bleeding Academic Research Consortium type 3 or 5. Outcomes from 12 to 24 months after PCI were compared according to the DAPT score.. Of 11,289 patients that were event-free after the first year, 6,882 and 4,407 patients had low (<2) and high (≥2) DAPT scores, respectively. Compared with a low DAPT score, patients with a high DAPT score had a higher rate of the composites of myocardial infarction or stent thrombosis (0.70% vs. 1.55%; p < 0.0001). The rate of Bleeding Academic Research Consortium type 3 or 5 bleeding was 0.54% and 0.30% in the low and high DAPT score groups, respectively (p = 0.058). The effect of ticagrelor versus aspirin monotherapy on primary ischemic and bleeding endpoints during the second year were no different among the 2 groups.. The DAPT score can stratify ischemic but not bleeding risk in a contemporary PCI population during the second year. The score did not provide additional value for selection of antiplatelet strategy beyond the first year.

Topics: Acute Coronary Syndrome; Aged; Clinical Decision Rules; Clinical Decision-Making; Coronary Artery Disease; Coronary Thrombosis; Drug Administration Schedule; Dual Anti-Platelet Therapy; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Predictive Value of Tests; Progression-Free Survival; Prospective Studies; Risk Assessment; Risk Factors; Stents; Ticagrelor; Time Factors

This prospective (April 2013-December 2020) parallel assignment clinical trial focuses on ST-Elevation Myocardial Infarction (STEMI) patient outcomes. The clinical trial includes 1500 STEMI patients from two hospitals in the Eastern Province of Saudi Arabia. Patients are assigned to one of two groups; the control arm receives conventional therapy with clopidogrel, while in the active arm the Spartan RX CYP2C19 assay is used to determine the *2 genotype. Carriers of a CYP2C19*2 loss-of-function allele receive prasugrel or ticagrelor, while non-carriers are treated with clopidogrel. Follow-up is one year after primary PCI. The primary end point is the number of patients who develop an adverse major cardiovascular event, including recurrent MI, non-fatal stroke, cardiovascular death, or major bleeding one year after PCI.. The risk of stent thrombosis in PCI patients is usually reduced by dual anti-platelet therapy, comprising aspirin and a P2Y12 inhibitor, such as clopidogrel. However, clopidogrel requires activation by the cytochrome P450 enzyme, CYP2C19. Approximately 20% of the population are unable to activate clopidogrel as they possess the CYP2C19*2 loss-of function (LoF) allele. The primary goal of this trial is to study the benefits of treating only those patients that cannot activate clopidogrel with an alternative that has shown to be a more effective platelet inhibitor and does not require bioactivation by the cytochrome P450 enzyme. We expect an improvement in net clinical benefit outcome in the active arm patients, thus supporting pharmacogenetic testing in PCI patients post STEMI.. Trial registration name is "Bedside Testing of CYP2C19 Gene for Treatment of Patients with PCI with Antiplatelet Therapy" (number NCT01823185) retrospectively registered with clinicaltrials.gov on April 4, 2013. This trial is currently at the patient recruitment stage.

Topics: Clinical Decision-Making; Clopidogrel; Coronary Thrombosis; Cytochrome P-450 CYP2C19; Humans; Multicenter Studies as Topic; Patient Selection; Percutaneous Coronary Intervention; Pharmacogenomic Testing; Pharmacogenomic Variants; Platelet Aggregation Inhibitors; Point-of-Care Testing; Polymorphism, Genetic; Prasugrel Hydrochloride; Predictive Value of Tests; Prospective Studies; Randomized Controlled Trials as Topic; Saudi Arabia; ST Elevation Myocardial Infarction; Stents; Ticagrelor; Treatment Outcome

The relative merits of ticagrelor as compared with prasugrel in patients with acute coronary syndromes for whom invasive evaluation is planned are uncertain.. In this multicenter, randomized, open-label trial, we randomly assigned patients who presented with acute coronary syndromes and for whom invasive evaluation was planned to receive either ticagrelor or prasugrel. The primary end point was the composite of death, myocardial infarction, or stroke at 1 year. A major secondary end point (the safety end point) was bleeding.. A total of 4018 patients underwent randomization. A primary end-point event occurred in 184 of 2012 patients (9.3%) in the ticagrelor group and in 137 of 2006 patients (6.9%) in the prasugrel group (hazard ratio, 1.36; 95% confidence interval [CI], 1.09 to 1.70; P = 0.006). The respective incidences of the individual components of the primary end point in the ticagrelor group and the prasugrel group were as follows: death, 4.5% and 3.7%; myocardial infarction, 4.8% and 3.0%; and stroke, 1.1% and 1.0%. Definite or probable stent thrombosis occurred in 1.3% of patients assigned to ticagrelor and 1.0% of patients assigned to prasugrel, and definite stent thrombosis occurred in 1.1% and 0.6%, respectively. Major bleeding (as defined by the Bleeding Academic Research Consortium scale) was observed in 5.4% of patients in the ticagrelor group and in 4.8% of patients in the prasugrel group (hazard ratio, 1.12; 95% CI, 0.83 to 1.51; P = 0.46).. Among patients who presented with acute coronary syndromes with or without ST-segment elevation, the incidence of death, myocardial infarction, or stroke was significantly lower among those who received prasugrel than among those who received ticagrelor, and the incidence of major bleeding was not significantly different between the two groups. (Funded by the German Center for Cardiovascular Research and Deutsches Herzzentrum München; ISAR-REACT 5 ClinicalTrials.gov number, NCT01944800.).

Topics: Acute Coronary Syndrome; Aged; Coronary Thrombosis; Female; Hemorrhage; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Stents; Stroke; Ticagrelor

It is unknown whether patients undergoing primary percutaneous coronary intervention (PCI) benefit from genotype-guided selection of oral P2Y. We conducted a randomized, open-label, assessor-blinded trial in which patients undergoing primary PCI with stent implantation were assigned in a 1:1 ratio to receive either a P2Y. For the primary analysis, 2488 patients were included: 1242 in the genotype-guided group and 1246 in the standard-treatment group. The primary combined outcome occurred in 63 patients (5.1%) in the genotype-guided group and in 73 patients (5.9%) in the standard-treatment group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.0 to 0.7; P<0.001 for noninferiority). The primary bleeding outcome occurred in 122 patients (9.8%) in the genotype-guided group and in 156 patients (12.5%) in the standard-treatment group (hazard ratio, 0.78; 95% CI, 0.61 to 0.98; P = 0.04).. In patients undergoing primary PCI, a

Topics: Administration, Oral; Aged; Clopidogrel; Coronary Thrombosis; Cytochrome P-450 CYP2C19; Female; Genotype; Hemorrhage; Humans; Intention to Treat Analysis; Male; Middle Aged; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Precision Medicine; Purinergic P2Y Receptor Antagonists; Single-Blind Method; ST Elevation Myocardial Infarction; Stents; Ticagrelor

Although switching between ticagrelor and clopidogrel is common in clinical practice, the efficacy and safety of this de-escalation remain controversial.. We assessed the occurrences, reasons, and outcomes of switching from ticagrelor to clopidogrel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing successful primary percutaneous coronary intervention (PCI).. A total of 653 patients with STEMI were randomly assigned to receive loading dose of ticagrelor or clopidogrel before PCI and then received maintenance dose, respectively, for 12 months follow-up. The primary outcome was major adverse cardiac events (MACE), including cardiovascular death, nonfatal myocardial infarction, and stroke. The secondary outcome included unexpected rehospitalization for angina, coronary revascularization, and stent thrombosis. The safety outcome was bleeding described by the Bleeding Academic Research Consortium (BARC) criteria.. A total of 602 participants completed the study. The rate of switching from ticagrelor to clopidogrel was 48.6% and the main reason was financial burden. The rate of secondary ischemic events in the de-escalation group was higher than that in the ticagrelor group (15.1% vs 5.6%, P = 0.008), but lower than that in the clopidogrel group (15.1% vs 24.6%, P = 0.03), while there were no significant differences in MACE among the three groups (P = 0.16). De-escalation, ticagrelor, and clopidogrel did not cause significant differences in the rates of major bleeding among the three groups (BARC ≥ 2, P = 0.34).. Switching from ticagrelor to clopidogrel is very common in patients with STEMI in China. De-escalation might be safe but associated with high risk of ischemic events as compared to ticagrelor.

Topics: Aged; China; Clopidogrel; Coronary Thrombosis; Drug Costs; Drug Substitution; Female; Hemorrhage; Humans; Male; Middle Aged; Patient Readmission; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Recurrence; Risk Factors; ST Elevation Myocardial Infarction; Stroke; Ticagrelor; Time Factors; Treatment Outcome

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

We evaluated the relationship of renal function and ischaemic and bleeding risk as well as the efficacy and safety of ticagrelor in stable patients with prior myocardial infarction (MI).. Patients with a history of MI 1-3 years prior from PEGASUS-TIMI 54 were stratified based on estimated glomerular filtration rate (eGFR), with <60 mL/min/1.73 m(2) pre-specified for analysis of the effect of ticagrelor on the primary efficacy composite of cardiovascular death, MI, or stroke (major adverse cardiovascular events, MACE) and the primary safety endpoint of TIMI major bleeding. Of 20 898 patients, those with eGFR <60 (N = 4849, 23.2%) had a greater risk of MACE at 3 years relative to those without, which remained significant after multivariable adjustment (hazard ratio, HRadj 1.54, 95% confidence interval, CI 1.27-1.85, P < 0.001). The relative risk reduction in MACE with ticagrelor was similar in those with eGFR <60 (ticagrelor pooled vs. placebo: HR 0.81; 95% CI 0.68-0.96) vs. ≥60 (HR 0.88; 95% CI 0.77-1.00, Pinteraction = 0.44). However, due to the greater absolute risk in the former group, the absolute risk reduction with ticagrelor was higher: 2.7 vs. 0.63%. Bleeding tended to occur more frequently in patients with renal dysfunction. The absolute increase in TIMI major bleeding with ticagrelor was similar in those with and without eGFR <60 (1.19 vs. 1.43%), whereas the excess of minor bleeding tended to be more pronounced (1.93 vs. 0.69%).. In patients with a history of MI, patients with renal dysfunction are at increased risk of MACE and consequently experience a particularly robust absolute risk reduction with long-term treatment with ticagrelor.

Topics: Adenosine; Aged; Coronary Artery Disease; Coronary Thrombosis; Drug Administration Schedule; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Renal Insufficiency, Chronic; Risk Factors; Ticagrelor; Treatment Outcome

The aim of this landmark exploratory analysis, ATLANTIC-H(24), was to evaluate the effects of pre-hospital ticagrelor during the first 24 h after primary percutaneous coronary intervention (PCI) in the ATLANTIC (Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial infarction to open the Coronary artery) study.. The ATLANTIC trial in patients with ongoing ST-segment elevation myocardial infarction showed that pre-hospital ticagrelor was safe but did not improve pre-PCI coronary reperfusion compared with in-hospital ticagrelor. We hypothesized that the effect of pre-hospital ticagrelor may not have manifested until after PCI due to the rapid transfer time (31 min).. The ATLANTIC-H(24) analysis included 1,629 patients who underwent PCI, evaluating platelet reactivity, Thrombolysis In Myocardial Infarction flow grade 3, ≥ 70% ST-segment elevation resolution, and clinical endpoints over the first 24 h.. Following PCI, largest between-group differences in platelet reactivity occurred at 1 to 6 h; coronary reperfusion rates numerically favored pre-hospital ticagrelor, and the degree of ST-segment elevation resolution was significantly greater in the pre-hospital group (median, 75.0% vs. 71.4%; p = 0.049). At 24 h, the composite ischemic endpoint was lower with pre-hospital ticagrelor (10.4% vs. 13.7%; p = 0.039), as were individual endpoints of definite stent thrombosis (p = 0.0078) and myocardial infarction (p = 0.031). All endpoints except death (1.1% vs. 0.2%; p = 0.048) favored pre-hospital ticagrelor, with no differences in bleeding events.. The effects of pre-hospital ticagrelor became apparent after PCI, with numerical differences in platelet reactivity and immediate post-PCI reperfusion, associated with reductions in ischemic endpoints, over the first 24 h, whereas there was a small excess of mortality. (Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial infarction to open the Coronary artery [ATLANTIC, NCT01347580]).

Topics: Adenosine; Adult; Aged; Ambulances; Coronary Thrombosis; Double-Blind Method; Emergency Medical Services; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Recurrence; ST Elevation Myocardial Infarction; Ticagrelor; Time Factors; Time-to-Treatment; Treatment Outcome

Ticagrelor improves the clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). However, few studies have directly compared the efficacy and safety of ticagrelor against clopidogrel, an oral, thienopyridine-class antiplatelet drug. This study compared the efficacy and safety of ticagrelor and clopidogrel in patients with STEMI undergoing PPCI.. We enrolled 400 patients with STEMI undergoing PPCI at the Zhujiang Hospital of Southern Medical University and the First Hospital of Qinhuangdao, China, between January 01, 2013 and April 30, 2015. All patients received 300 mg of aspirin and were randomized to receive one of the following treatments: (1) a loading dose of clopidogrel (600 mg) before PPCI followed by clopidogrel (75 mg once daily for 1 year) post PPCI or (2) a loading dose of ticagrelor (180 mg) before PPCI followed by ticagrelor (90 mg twice daily for 1 year) post PPCI. Some patients were treated by intracoronary bolus of a glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitor [tirofiban (10 μg/kg) plus maintenance infusion (0.15 μg·kg·min) for 24-36 hours] in accordance with specified guidelines. The primary end points evaluated were major adverse cardiovascular and cerebrovascular event (MACCE) [defined as a composite of overall death, myocardial infarction (MI), unplanned revascularization, or stroke], stent thrombosis, and the composite end point of CV death, nonfatal MI, and stroke. The supplemental use of GPIIb/IIIa inhibitors in the clopidogrel and ticagrelor groups was monitored as another study end point, although the secondary safety end point evaluated was the incidence of bleeding events.. Compared with the clopidogrel-treated group, ticagrelor treatment significantly reduced the incidence of MACCE [5 vs. 14; odds ratio (OR), 0.341; 95% confidence interval (CI), 0.120-0.964; P = 0.034] and the composite end points of cardiovascular death, nonfatal MI, and stroke (4 vs. 13; OR, 0.294; 95% CI, 0.094-0.916; P = 0.026). Fewer patients in the ticagrelor group received GPIIb/IIIa inhibitors after PPCI compared with those in the clopidogrel group (10 vs. 21; OR, 0.449; 95% CI, 0.206-0.979; P = 0.040). However, there were no significant differences between the groups in the incidences of all-cause mortality, nonfatal MI, unplanned revascularization, stroke, stent thrombosis (P = 0.522, P = 0.246, P = 0.246, P = 0.217, P = 0.246, respectively), or bleeding events (10 vs. 7; OR, 1.451; 95% CI, 0.541-3.891; P = 0.457).. Among patients with STEMI undergoing PPCI, ticagrelor reduces the incidence of MACCE and the composite end point of cardiovascular death, nonfatal MI, and stroke compared with clopidogrel. Ticagrelor also reduces the need for GPIIb/IIIa inhibitors. However, no significant difference was observed in the risk of bleeding between the 2 groups.

Topics: Adenosine; Aged; Chi-Square Distribution; China; Clopidogrel; Coronary Thrombosis; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Odds Ratio; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recurrence; Risk Factors; ST Elevation Myocardial Infarction; Stroke; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

In acute coronary syndromes (ACS), a dual antiplatelet regimen with an adenosine diphosphate (ADP) receptor antagonist plus aspirin has become the cornerstone of treatment. The third-generation thienopyridine prasugrel and the cyclopentyl-triazolo-pyrimidine ticagrelor provide a greater, more rapid and consistent platelet inhibition compared to their predecessor clopidogrel. Based on their advantages over clopidogrel in two landmark studies, both drugs received a class I recommendation for their use in ACS patients with and without ST segment elevation. Due to differences in ACS populations and conditions investigated, the relative merits of ticagrelor versus prasugrel in the treatment of ACS patients with planned invasive strategy cannot be reliably estimated from independent trials. To date, no direct head-to-head comparison of ticagrelor and prasugrel in terms of clinical outcome exists. The aim of this multicenter, randomized, open-label trial is to assess whether ticagrelor is superior to prasugrel in ACS patients with planned invasive strategy.

Topics: Acute Coronary Syndrome; Adenosine; Clinical Protocols; Coronary Thrombosis; Drug Administration Schedule; Fibrinolytic Agents; Germany; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Research Design; Stents; Stroke; Thiophenes; Ticagrelor; Time Factors; Time-to-Treatment; Treatment Outcome

Ticagrelor reduces thrombotic events compared with clopidogrel in patients with acute coronary syndrome, but may also increase bleeding complications. Coronary artery bypass grafting (CABG)-related bleeding complications have not previously been compared in clopidogrel and ticagrelor-treated patients outside the controlled environment of clinical trials.. Four hundred and five consecutive CABG patients with acute coronary syndrome were included in a prospective observational study. The patients were treated with aspirin and ticagrelor (n = 173) or aspirin and clopidogrel (n = 232). Ticagrelor/clopidogrel was discontinued 5 days before surgery whenever deemed possible. Major bleeding complications according to modified blood conservation using antifibrinolytics in a randomized trial criteria (postoperative blood loss >1500 ml/12 h, re-exploration, red blood cell transfusion >10 units or death because of bleeding) were compared in all patients and when ticagrelor/clopidogrel was discontinued ≥5 days (n = 280), 2-4 days (n = 40) or 0-1 day before surgery (n = 85).. Major bleeding complications did not differ significantly between ticagrelor- and clopidogrel-treated patients when all patients were compared (14.5 vs 13.8%, P = 0.89). Likewise, there were no significant differences between ticagrelor and clopidogrel when either drug was discontinued ≥5 days before surgery (6.8 vs 9.9%, P = 0.40) or 2-4 days before surgery (6.3 vs 25.0%, P = 0.21). When ticagrelor/clopidogrel was discontinued 0-1 day before surgery, there was a strong trend towards higher incidence of major bleeding in ticagrelor-treated patients (41.0 vs 21.7%, P = 0.063).. There was no difference in major bleeding complications overall or when ticagrelor or clopidogrel was used in accordance with guidelines. In patients on dual antiplatelet medication up to 1 day before surgery, there tended to be more bleeding complications in ticagrelor-treated patients.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Clopidogrel; Coronary Artery Bypass; Coronary Thrombosis; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Prospective Studies; Ticagrelor; Ticlopidine

The PLATO (Platelet Inhibition and Patient Outcomes) angiographic substudy sought to compare the efficacy of ticagrelor versus clopidogrel with respect to angiographic outcomes before and after PCI in the setting of acute coronary syndrome.. Greater platelet inhibition has been associated with improved angiographic outcomes before and after percutaneous coronary intervention (PCI). Therefore, it was hypothesized that treatment with ticagrelor, which achieves more rapid, higher, and more consistent platelet inhibition, would be associated with improved angiographic outcomes when compared with those of clopidogrel treatment.. The angiographic cohort consists of 2,616 patients drawn from the 18,624-patient PLATO trial. Clopidogrel naïve or pre-treated patients were randomized to 180 mg of ticagrelor or 300 mg of clopidogrel (75 mg for clopidogrel pre-treated patients). PCI patients were administered, as per treatment group: 1) an additional 90 mg of ticagrelor if >24 h following the initial loading dose; or 2) an optional further 300 mg of clopidogrel or placebo (total 600 mg) prior to PCI. The substudy primary endpoint was the incidence of post-PCI TIMI (Thrombolysis In Myocardial Infarction) myocardial perfusion grade 3 (TMPG 3) among patients who received a study drug prior to PCI.. In total, 21.3% of patients were pretreated with clopidogrel prior to randomization. There was a short time interval between randomization and PCI (median: 0.68 [interquartile range (IQR): 0.30 to 2.21] h) among all patients. Post-PCI TMPG 3 was similar between the ticagrelor and clopidogrel groups (47.1% vs. 46.9%; p = 0.96). Likewise, the following pre-PCI outcomes were similar in the ticagrelor and clopidogrel groups, respectively: TMPG 3 (30.5% vs. 31.2%), TIMI flow grade 3 (37.1% vs. 39.3%), corrected TIMI frame count (median: 100 vs. 71 frames), TIMI thrombus grade 0 (24.1% vs. 27.6%), minimum lumen diameter (median: 0.3 [IQR: 0.0 to 0.6] vs. 0.3 [IQR: 0.0 to 0.6] mm) and percentage of diameter stenosis (median: 89 [IQR: 78 to 100] vs. 89 [IQR: 77 to 100]).. Neither coronary flow nor myocardial perfusion, evaluated on coronary angiograms performed before or following PCI procedures within a few hours after the start of oral antiplatelet treatment in the setting of acute coronary syndromes, demonstrated a difference with ticagrelor versus clopidogrel. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872).

Topics: Acute Coronary Syndrome; Adenosine; Administration, Oral; Aged; Clopidogrel; Coronary Angiography; Coronary Circulation; Coronary Stenosis; Coronary Thrombosis; Coronary Vessels; Double-Blind Method; Female; Humans; Logistic Models; Male; Middle Aged; Myocardial Perfusion Imaging; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Predictive Value of Tests; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

We aimed to describe the effects of ticagrelor versus clopidogrel on stent thrombosis in the Platelet Inhibition and Patient Outcomes (PLATO) trial.. Of 18 624 patients hospitalized for acute coronary syndromes, 11 289 (61%) had at least 1 intracoronary stent. Ticagrelor reduced stent thrombosis compared with clopidogrel across all definitions: definite, 1.37% (n=71) versus 1.93% (n=105; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.50-0.90; P=0.0091); definite or probable, 2.21% (n=118) versus 2.87% (n=157; HR, 0.75; 95% CI, 0.59-0.95; P=0.017); and definite, probable, and possible, 2.94% (n=154) versus 3.77 (n=201; HR, 0.77; 95% CI, 0.62-0.95). The reduction in definite stent thrombosis was consistent regardless of acute coronary syndrome type, presence of diabetes mellitus, stent type (drug-eluting or bare metal stent), CYP2C19 genetic status, loading dose of aspirin, dose of clopidogrel before randomization, and use of glycoprotein IIb/IIIa inhibitors at randomization. The reduction in stent thrombosis with ticagrelor was numerically greater for late (>30 days; HR, 0.48; 95% CI, 0.24-0.96) and subacute (4 hours-30 days; HR, 0.60; 95% CI, 0.39-0.93) compared with acute (<24 hours; HR, 0.94; 95% CI, 0.43-2.05) stent thrombosis or for patients compliant to therapy (ie, taking blinded study treatment ≥80% of the time) compared with less compliant patients. Randomization to ticagrelor was a strong independent inverse predictor of definite stent thrombosis (HR, 0.65; 95% CI, 0.48-0.88).. Ticagrelor compared with clopidogrel reduces the incidence of stent thrombosis in patients with acute coronary syndromes, with consistent benefit across a broad range of patient, stent, and treatment characteristics.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Clopidogrel; Coronary Thrombosis; Double-Blind Method; Female; Follow-Up Studies; Heart Diseases; Humans; Internationality; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Purinergic P2Y Receptor Antagonists; Risk Factors; Stents; Ticagrelor; Ticlopidine; Treatment Outcome

The study aimed to compare the antiplatelet action of ticagrelor with prasugrel in acute coronary syndrome (ACS) patients with high on-treatment platelet reactivity (HTPR) while on clopidogrel after percutaneous coronary intervention (PCI).. Newer P2Y12 inhibitors like prasugrel and ticagrelor provide stronger platelet inhibition compared with clopidogrel. Both agents are efficacious in patients with HTPR while on clopidogrel, but direct comparison between them has not yet been reported.. In a prospective, single-center, single-blind study, 44 (of 139 screened, 31.7%) ACS patients with HTPR while on clopidogrel 24 h post-PCI were randomized to either ticagrelor 90 mg twice daily or prasugrel 10 mg once daily for 15 days with a crossover directly to the alternate treatment for another 15 days. HTPR was defined as platelet reactivity units (PRU) ≥ 235 as assessed by the VerifyNow P2Y12 function assay.. The primary endpoint of platelet reactivity at the end of the 2 treatment periods was lower for ticagrelor (32.9 PRU, 95% confidence interval [CI]: 18.7 to 47.2) compared with prasugrel (101.3 PRU, 95% CI: 86.8 to 115.7) with a least squares mean difference of -68.3 PRU (95% CI: -88.6 to -48.1; p < 0.001). The secondary endpoint of HTPR rate was 0% for ticagrelor and 2.4% for prasugrel (1 of 42, p = 0.5). No patient exhibited a major bleeding event at either treatment group.. In patients with ACS exhibiting HTPR while on clopidogrel 24 h post-PCI, ticagrelor produces a significantly higher platelet inhibition compared with prasugrel. (Ticagrelor Versus Prasugrel in Acute Coronary Syndromes After Percutaneous Coronary Intervention; NCT01360437).

Topics: Acute Coronary Syndrome; Adenosine; Aged; Angioplasty, Balloon, Coronary; Clopidogrel; Coronary Thrombosis; Cross-Over Studies; Female; Humans; Male; Middle Aged; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticagrelor; Ticlopidine

Aspirin and clopidogrel are recommended for patients with acute coronary syndromes (ACS) or undergoing coronary stenting. Ticagrelor, a reversible oral P2Y12-receptor antagonist, provides faster, greater, and more consistent platelet inhibition than clopidogrel and may be useful for patients with acute ST-segment elevation (STE) ACS and planned primary percutaneous coronary intervention.. Platelet Inhibition and Patient Outcomes (PLATO), a randomized, double-blind trial, compared ticagrelor with clopidogrel for the prevention of vascular events in 18 624 ACS patients. This report concerns the 7544 ACS patients with STE or left bundle-branch block allocated to either ticagrelor 180-mg loading dose followed by 90 mg twice daily or clopidogrel 300-mg loading dose (with provision for 300 mg clopidogrel at percutaneous coronary intervention) followed by 75 mg daily for 6 to 12 months. The reduction of the primary end point (myocardial infarction, stroke, or cardiovascular death) with ticagrelor versus clopidogrel (10.8% versus 9.4%; hazard ratio [HR], 0.87; 95% confidence interval, 0.75 to 1.01; P=0.07) was consistent with the overall PLATO results. There was no interaction between presentation with STE/left bundle-branch block and randomized treatment (interaction P=0.29). Ticagrelor reduced several secondary end points, including myocardial infarction alone (HR, 0.80; P=0.03), total mortality (HR, 0.82; P=0.05), and definite stent thrombosis (HR, 0.66; P=0.03). The risk of stroke, low in both groups, was higher with ticagrelor (1.7% versus 1.0%; HR,1.63; 95% confidence interval, 1.07 to 2.48; P=0.02). Ticagrelor did not affect major bleeding (HR, 0.98; P=0.76).. In patients with STE-ACS and planned primary percutaneous coronary intervention, the effects of ticagrelor were consistent with those observed in the overall PLATO trial.. URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00391872.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Angioplasty, Balloon, Coronary; Clopidogrel; Coronary Thrombosis; Electrocardiography; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Risk Factors; Ticagrelor; Ticlopidine; Treatment Outcome

Topics: Clinical Decision-Making; Clopidogrel; Coronary Thrombosis; Drug Substitution; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Ticagrelor; Time Factors; Treatment Outcome

To compare the risk of cardiovascular events between patients with two CYP2C19 loss-of-function alleles who were prescribed ticagrelor or clopidogrel after percutaneous coronary intervention (PCI).. Patients with two loss-of-function alleles based on the CYP2C19 genotype were selected from patients enrolled in a retrospective institutional registry. Propensity score matching using logistic regression was performed to adjust for bias between patients prescribed ticagrelor or clopidogrel. Multivariate Cox regression was used to compare the risk of adverse events in the ticagrelor and clopidogrel groups. The primary outcome was the incidence of major adverse cardiac events plus any repeat target vessel revascularization within 12 months after PCI. The safety outcomes were minor and major bleeding events.. From 1518 patients carrying two loss-of-function alleles based on the CYP2C19 genotype who underwent PCI, 638 patients treated with ticagrelor or clopidogrel were successfully propensity-score matched. The primary outcome occurred in 25 patients (7.8%) in the ticagrelor group and 47 (14.7%) in the clopidogrel group. The risk of the primary outcome was significantly lower in the ticagrelor group versus the clopidogrel group (HR 0.466, 95% CI 0.286-0.759, p = 0.002). The incidence of major bleeding events did not significantly differ between the ticagrelor and clopidogrel groups (0.3% and 0.9%, respectively), while the ticagrelor group had a higher risk of minor bleeding events (HR 1.959, 95% CI 1.396-2.750, p < 0.001).. In patients with two CYP2C19 loss-of-function alleles, ticagrelor was more effective than clopidogrel in preventing cardiovascular events, while the two antiplatelet agents were associated with similar incidences of major bleeding.

Topics: Aged; Clopidogrel; Coronary Artery Disease; Coronary Thrombosis; Cytochrome P-450 CYP2C19; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Pharmacogenomic Variants; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Stents; Ticagrelor; Time Factors; Treatment Outcome

Topics: Antigens, Human Platelet; Arginine; Aspirin; Autoantibodies; Combined Modality Therapy; Coronary Thrombosis; Drug Substitution; Drug Therapy, Combination; Eptifibatide; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Pipecolic Acids; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Platelet Transfusion; Purpura, Thrombocytopenic, Idiopathic; Shock, Cardiogenic; ST Elevation Myocardial Infarction; Stents; Sulfonamides; Thrombectomy; Thrombolytic Therapy; Thrombosis; Ticagrelor; Warfarin

To compare the effect of ticagrelor with clopidogrel in reducing the risk of ischemic cardiovascular events in patients with late or very late stent thrombosis (LST/VLST) after primary percutaneous coronary intervention (PCI).. A total of 4538 patients with acute coronary syndrome were screened for angiographically determined LST/VLST. Two hundred and forty-one patients were included in the analysis and grouped according to ticagrelor (n = 81) or clopidogrel (n = 160) at discharge. The clinical outcome was major adverse cardiovascular events (MACE) defined as death, myocardial infarction (MI), ischemic stroke, and revascularization during the 1-yr follow-up period.. After propensity score matching, 65 pairs were generated. The incidence of MACE was significantly lower in the ticagrelor group compared with the clopidogrel group (9.3% vs. 21.5%, log-rank p = 0.048). However, no difference was observed in event rates of death, MI, ischemic stroke, and revascularization between the ticagrelor group and the clopidogrel group.. Following successful primary PCI, patients with LST/VLST who received ticagrelor had fewer ischemic cardiovascular events at 1-yr follow-up, compared with those who received clopidogrel.

Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Coronary Thrombosis; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Risk Assessment; Risk Factors; Stents; Ticagrelor; Time Factors; Treatment Outcome

This study sought to analyze the impact of the preprocedural thrombolysis in myocardial infarction (TIMI) flow on clinical outcome in patients with ST-elevation myocardial infarction (STEMI).. Previous studies have shown that the TIMI flow 0/1 prior to primary percutaneous coronary intervention (PCI) is associated with a poor clinical outcome. However, it is unclear whether the same is true in patients with ongoing STEMI of less than 6 hr duration, rapid reperfusion, and modern guideline-adherent therapy.. The ATLANTIC study compared prehospital versus inhospital treatment with ticagrelor in patients with acute STEMI. For this analysis, patients were divided into three groups according to the preprocedural TIMI flow grade of the infarct vessel: TIMI 0/1, TIMI 2, and TIMI 3.. From a total of 1,680 patients, 1,113 had TIMI 0/1, 279 TIMI 2, and 288 TIMI 3 flow before primary PCI. At 30 days, the composite ischemic endpoint (5.5, 2.9, and 2.1%, p < .05) and all-cause death (3.0, 1.4, and 2.1%, p = .30) were highest in patients with TIMI flow 0/1. After adjustment, preprocedural TIMI flow <3 (versus 3) was not an independent predictor of major adverse ischemic events within 30 days (odds ratio 1.89, 95% confidence interval 0.74-4.85). However, definite stent thrombosis occurred only in patients with initial TIMI flow 0/1 (1.0%). Among these patients, those with prehospital administration of ticagrelor were less often affected (0.3% vs. 1.3%, p < .05).. In this post-hoc analysis, preprocedural TIMI flow was not independently associated with a higher rate of adverse ischemic events.

Topics: Aged; Cause of Death; Coronary Circulation; Coronary Thrombosis; Drug Administration Schedule; Europe; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Ticagrelor; Time Factors; Treatment Outcome

Topics: Clinical Trials, Phase IV as Topic; Coronary Artery Disease; Coronary Thrombosis; Hemorrhage; Humans; Medication Adherence; Multicenter Studies as Topic; Patient Safety; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Risk Factors; Ticagrelor; Treatment Outcome

International guidelines recommend ticagrelor over clopidogrel as preferred antiplatelet agent in patients following coronary stenting. However, no large real-life evidence is available in East Asians in general, and Chinese in particular, with regard to associated clinical outcomes. The present study aimed to assess the early and delayed outcomes after ticagrelor versus clopidogrel in post stenting Chinese patients.. We conducted the pre-specified interim analysis of Comparison Of Efficacy and Safety Between TIcagrelor and Clopidogrel In Chinese (COSTIC), the ongoing prospective, observational, single-center trial. Primary outcomes include first occurrence of myocardial infarction, stroke, vascular death and Bleeding Academic Research Consortium (BARC) scale bleeding event. Propensity score matching (PSM) was carried out to adjust for differences in baseline characteristics between treatment arms.. In total, 4,465 patients were enrolled. After PSM, the patients prescribed with ticagrelor had a lower incidence of primary efficacy endpoint relative to those with clopidogrel (0.6% vs. 1.4%, HR = 0.44, 95%CI: 0.22-0.89, p = 0.019) at 1 month, but similar at 7 days, 6 months and 12 months. Further analysis indicated that the difference only exists in the subgroup of acute myocardial infarction (AMI) patients. With regard to safety, ticagrelor consistently increased the risk of BARC type 2 bleeding compared to clopidogrel at 1 month, 6 months and 12 months.. These preliminary data indicate that ticagrelor is superior to clopidogrel with regard to major vascular thrombotic outcomes at 1 month, especially in the AMI population, but both groups are similar at 7 days, 6 months and 12 months. Ticagrelor consistently caused significantly more BARC type 2 bleeding.

Topics: Acute Coronary Syndrome; Aged; Asian People; China; Clopidogrel; Coronary Thrombosis; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Registries; Risk Assessment; Risk Factors; Stents; Ticagrelor; Time Factors; Treatment Outcome

Balancing ischemic and bleeding risk is an evolving framework.. Our objectives were to simulate changes in risks for adverse events and event-driven costs with use of ticagrelor or prasugrel versus clopidogrel according to varying levels of ischemic and bleeding risk. Using the validated PARIS risk functions, we estimated 1-year ischemic (myocardial infarction or stent thrombosis) and bleeding (Bleeding Academic Research Consortium types 3 or 5) event rates among PARIS study participants who underwent percutaneous coronary intervention with drug-eluting stent implantation for an acute coronary syndrome and were discharged with aspirin and clopidogrel (n=1497). Simulated changes in adverse events with ticagrelor or prasugrel were calculated by applying treatment effects from randomized trials for a 1-year time horizon. Event costs were estimated using National Inpatient Sample data. Net costs were calculated between antiplatelet therapy groups according to level of ischemic and bleeding risk. After weighting events for quality-of-life impact, we calculated event rates and costs for risk-tailored treatment versus clopidogrel under multiple drug pricing assumptions. One-year rates (per 1000 person-years) for ischemic events were 12.6, 24.1, and 66.1, respectively, among those at low (n=630), intermediate (n=536), and high (n=331) ischemic risk. Analogous bleeding rates were 11.0, 23.9, and 66.2, respectively, among low (n=728), intermediate (n=634), and high (n=135) bleeding risk patients. Mean per event costs were $22 174 (ischemic) and $12 203 (bleeding). When risks for ischemia matched or exceeded bleeding, simulated utility-weighted event rates favored ticagrelor/prasugrel, whereas clopidogrel reduced utility-weighted events when bleeding exceeded ischemic risk. One-year costs were sensitive to drug pricing assumptions, and risk-tailored treatment with either agent progressed from cost incurring to cost saving with increasing generic market share.. Tailoring antiplatelet therapy intensity to patient risk may improve health utility and could produce cost savings in the first year after percutaneous coronary intervention.. URL: https://www.clinicaltrials.gov . Unique identifier: NCT00998127.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Clinical Decision-Making; Clopidogrel; Coronary Thrombosis; Cost Savings; Cost-Benefit Analysis; Drug Costs; Drug-Eluting Stents; Europe; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Registries; Risk Assessment; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome; United States

Topics: Abciximab; Adult; Aspirin; Coronary Angiography; Coronary Thrombosis; Coronary Vessels; Female; Humans; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Ticagrelor; Tomography, Optical Coherence

Ticagrelor induces more potent platelet reactivity (PR) inhibition with reduced interindividual variability compared to clopidogrel. Although on-clopidogrel PR was shown to correlate with ischemia and bleeding events, no study has investigated the relationship between on-ticagrelor PR and outcome.. We aimed to evaluate the relationship between on-ticagrelor PR, assessed by the vasodilator-stimulated phosphoprotein index (VASP), and thrombotic and bleeding events in patients with acute coronary syndrome (ACS) treated by percutaneous coronary intervention (PCI).. We performed a prospective, multicenter observational study on patients treated with PCI for ACS. The VASP index was used to assess PR after ticagrelor loading dose (LD). The primary endpoint was the link between major adverse cardiovascular events (MACE) and PR.. Among the 530 patients with ACS included, 183 (34.5%) were admitted for ST elevation myocardial infarction. We observed high potency and limited interindividual variability after the ticagrelor LD (VASP 19.1% ± 16.6%). At 1 month, 21 (3.8%) MACE and 29 (5.5%) bleedings ≥ 2 according to the Bleedings Academic Research Consortium (BARC) scale were recorded. Neither MACE nor bleeding was associated with PR (P = .34 and P = .78, respectively). However, there was a strong association between PR and the occurrence of definite acute stent thrombosis (P = .03). Platelet reactivity was the only factor associated with acute definite stent thrombosis.. In patients receiving a ticagrelor LD while undergoing PCI for ACS, PR using the VASP did not predict MACE or bleeding, but it was significantly associated with the occurrence of definite acute stent thrombosis.

Topics: Acute Coronary Syndrome; Aged; Biomarkers; Blood Platelets; Cell Adhesion Molecules; Coronary Thrombosis; Female; France; Hemorrhage; Humans; Male; Microfilament Proteins; Middle Aged; Non-ST Elevated Myocardial Infarction; Percutaneous Coronary Intervention; Phosphoproteins; Platelet Activation; Platelet Aggregation Inhibitors; Prospective Studies; Risk Factors; ST Elevation Myocardial Infarction; Stents; Ticagrelor; Time Factors; Treatment Outcome

The HEAT-PPCI trial compared bivalirudin and unfractionated heparin in patients undergoing primary percutaneous coronary intervention (PPCI). The aim of this study was to report pre-specified, secondary analyses comparing the effects of P2Y12 inhibiting agents on platelet reactivity and clinical events.. All patients received preprocedural oral antiplatelet therapy. During the early stages of the trial, the P2Y12 inhibitor of choice was prasugrel with some use of clopidogrel. Later, routine therapy switched to ticagrelor. For cases performed during working hours, multiple electrode aggregometry (MEA) was used to assess ADP-induced platelet aggregation at the end of the index procedure. The effect of P2Y12 inhibitors on the primary efficacy (major adverse cardiac events [MACE]) and safety (major bleeding) outcomes was assessed in all patients. Multiple logistic regression was used to adjust for differences in baseline characteristics. With MEA data from 469 patients, prasugrel therapy resulted in significantly greater suppression of ADP-induced platelet aggregation at 40 U (23, 78) (median; interquartile range [IQR]) when compared against ticagrelor 75 U (41, 100.75); p<0.001 or clopidogrel 79 U (56, 96); p<0.001. In the entire study population (N=1,803), prasugrel therapy was associated with significantly fewer MACE (26/497; 5.2%) in comparison to ticagrelor (83/1,123; 7.4%) or clopidogrel (18/183; 9.8%); odds ratio (OR) 0.64, confidence interval (CI): 0.41-0.99, p=0.045. For major bleeding, there were no significant differences among the three groups - clopidogrel (3/183; 1.6%), prasugrel (13/497; 2.6%) and ticagrelor (43/1,123; 3.8%); OR 0.73, CI: 0.39-1.35, p=0.31. Patients treated with clopidogrel had more high-risk features and clopidogrel use was more common as an alternative to prasugrel. After adjustment, there were no significant differences in the rates of MACE (OR 0.70, CI: 0.41-1.21, p=0.20) or major bleeding (OR 0.80, CI: 0.41-1.60, p=0.53).. In HEAT-PPCI, patients who received prasugrel (rather than clopidogrel or ticagrelor) had significantly greater suppression of ADP-induced platelet aggregation at the end of the procedure. After adjustment for differences in baseline characteristics, there were no significant differences in ischaemic or bleeding outcomes among the antiplatelet therapies.

Topics: Anticoagulants; Clopidogrel; Coronary Thrombosis; Hemorrhage; Humans; Myocardial Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome

The effects of ticagrelor pretreatment in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI) is debated. This study investigated the effects of ticagrelor pretreatment on clinical outcomes in this patient group.. Patients with ST-segment-elevation myocardial infarction undergoing primary PCI were included from October 2010 to October 2014 in Sweden. Screening was done using the SWEDEHEART register (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies). A total of 7433 patients were included for analysis with 5438 patients receiving ticagrelor pretreatment and 1995 patients with ticagrelor given only in the catheterization laboratory. The primary end point of the study was 30-day event rates of a composite of all-cause mortality, myocardial infarction (MI), and stent thrombosis. Secondary end points were mortality, MI, or stent thrombosis alone and major in-hospital bleeding. Crude event rates showed no difference in 30-day composite end point (6.2% versus 6.5%;. Ticagrelor pretreatment versus ticagrelor given in the catheterization laboratory in patients with ST-segment-elevation myocardial infarction undergoing primary PCI did not improve the composite end point of all-cause mortality or MI or stent thrombosis or its individual components at 30 days.

Topics: Aged; Coronary Thrombosis; Drug Administration Schedule; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Recurrence; Registries; Risk Factors; ST Elevation Myocardial Infarction; Sweden; Ticagrelor; Time Factors; Treatment Outcome

Inflammatory bowel diseases have been recognized as predisposing factors to atherosclerosis and thrombotic events, involving both the venous and the arterial circulatory systems. We report the case of a 70-year-old man who presented with ST elevation myocardial infarction during the active phase of ulcerative colitis (UC). Because of the ongoing hematochezia, after successful revascularization of the culprit vessel, the patient was medicated with Clopidogrel, in place of one of the more powerful new oral P2Y

Topics: Abciximab; Aged; Angioplasty, Balloon, Coronary; Clopidogrel; Colitis, Ulcerative; Coronary Thrombosis; Humans; Male; Myocardial Infarction; Platelet Aggregation Inhibitors; Postoperative Complications; Stents; Ticagrelor

The aim of this study was to assess the feasibility and clinical results following a pre-specified bioresorbable scaffold (Absorb BVS) implantation strategy in patients with ST-segment elevation myocardial infarction (STEMI).. Concerns were raised about the safety of Absorb because a non-negligible rate of thrombosis was reported within 30 days and at midterm follow-up after primary percutaneous coronary intervention.. This was a prospective, multicenter study of patients with STEMI (<75 years of age with symptom onset <12 h) undergoing primary percutaneous coronary intervention with Absorb following a dedicated implantation protocol. The primary endpoint was a device-oriented composite endpoint of cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization within 30 days.. During the study period, 505 patients with STEMI (16.9% of the overall STEMI population) were treated with the Absorb BVS. The mean age was 56.6 ± 9.4 years, and 487 patients (96.4%) were in Killip class I or II at admission. According to the study protocol, direct Absorb implantation was feasible in 47 patients (9.3%), whereas post-dilatation was performed in 468 cases (92.7%). Procedural success was attained in 94.8% of the cases. Dual antiplatelet therapy with ticagrelor or prasugrel was administered at discharge in 481 patients (95.1%). At 30-day follow-up, the hierarchical device-oriented composite endpoint rate was 0.6% (0.4% cardiac death, 0.2% target vessel myocardial infarction and ischemia-driven target lesion revascularization). One episode (0.2%) of probable scaffold thrombosis was reported.. A pre-specified Absorb implantation strategy in real-world patients with STEMI undergoing primary percutaneous coronary intervention was feasible and associated with a low 30-day device-oriented composite endpoint rate. Mid- and long-term follow-up is strongly needed to eventually confirm these early results. (Use of BVS in ST-Segment Elevation Myocardial Infarction [STEMI]: The BVS STEMI STRATEGY-IT Prospective Registry [STRATEGY-IT]; NCT02601781).

Topics: Absorbable Implants; Adenosine; Aged; Angioplasty, Balloon, Coronary; Aspirin; Coronary Thrombosis; Drug Therapy, Combination; Female; Humans; Italy; Male; Middle Aged; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Prosthesis Design; Recurrence; Risk Factors; ST Elevation Myocardial Infarction; Ticagrelor; Time Factors; Treatment Outcome

The initial EROSION study (Effective Anti-Thrombotic Therapy Without Stenting: Intravascular Optical Coherence Tomography-Based Management in Plaque Erosion) demonstrated that patients with acute coronary syndrome caused by plaque erosion might be stabilized with aspirin and ticagrelor without stenting for ≤1 month. However, a long-term evaluation of outcomes is lacking. The aim of this study was to assess whether the initial benefit of noninterventional therapy for patients with acute coronary syndrome caused by plaque erosion is maintained for ≤1 year.. Among 53 patients who completed clinical follow-up, 49 underwent repeat optical coherence tomography imaging at 1 year. Median residual thrombus volume decreased significantly from 1 month to 1 year (0.3 mm. One-year follow-up optical coherence tomography demonstrated a further decrease in thrombus volume between 1-month and 1-year follow-up. A majority (92.5%) of patients with acute coronary syndrome caused by plaque erosion managed with aspirin and ticagrelor without stenting remained free of major adverse cardiovascular event for ≤1 year.. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02041650.

Topics: Acute Coronary Syndrome; Adenosine; Adult; Aspirin; Coronary Angiography; Coronary Artery Disease; Coronary Thrombosis; Coronary Vessels; Disease-Free Survival; Drug Therapy, Combination; Female; Fibrinolytic Agents; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Myocardial Revascularization; Plaque, Atherosclerotic; Platelet Aggregation Inhibitors; Predictive Value of Tests; Prospective Studies; Risk Factors; Thrombectomy; Ticagrelor; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Out-of-Hospital Cardiac Arrest (OHCA) and mild therapeutic hypothermia (MTH) have been linked to increased risk of Stent Thrombosis (ST) in comatose survivors who undergo percutaneous coronary intervention (PCI). In this sense, there is no formal recommendation about which antiplatelet regimen should be used in patients with acute coronary syndromes (ACS) after OHCA.. To compare the incidence of probable/definite ST and bleeding events between ticagrelor and clopidogrel, in patients with ACS under MTH after an OHCA.. From January 2010 to August 2016, 144 patients underwent MTH after an OHCA. Overall, 114 had an ACS (79%) and 98 (67,3%) were treated with primary PCI and stent implantation. Among them, 61 (62,2%) were treated with clopidogrel, and 32 (32,6%) with ticagrelor. During hospitalization, the incidence of probable or definite ST was significantly higher in patients receiving clopidogrel compared to ticagrelor (11,4% vs. 0%; p: 0.04), and no significant differences in any (28,6% vs. 25%; p: 0.645) or major bleeding (BARC 3 or 5) (11,4% vs. 12,5%; p: 0.685) were found. Hospital mortality did not differ between groups (26,2% vs. 25%; p: 0.862).. In this study, as compared to clopidogrel, ticagrelor was associated with a lower rate of ST, without differences in haemorrhagic events in patients with OHCA for an ACS under MTH. Similarly to other settings, ticagrelor might be a valid alternative to clopidogrel in these patients.

Topics: Adenosine; Aged; Clopidogrel; Coronary Thrombosis; Humans; Hypothermia, Induced; Male; Middle Aged; Out-of-Hospital Cardiac Arrest; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Factors; Stents; Ticagrelor; Ticlopidine

High rates of stent thrombosis (ST) have been reported in patients with out-of-hospital cardiac arrest (OHCA) who require a primary percutaneous coronary intervention (PCI). The aim of this study was to assess risk factors of ST in this population with a special focus on antiplatelet therapy administered during the acute phase.. We conducted a retrospective observational study in patients treated with primary PCI after OHCA between 2011 and 2013 in our center. All consecutive patients were treated with mild therapeutic hypothermia and dual antiplatelet therapy after primary angioplasty.. A total of 101 consecutive patients were included in the present analysis. Mean age was 61.3 ± 12.7 years and 75% of patients had an initial ventricular fibrillation. All patients received aspirin before PCI. P2Y12 inhibitors were administered after PCI and included clopidogrel (47.5%), prasugrel (21.8%) or ticagrelor (29.7%). The survival rate at discharge was 44.5%. We identified 11 cases (10.9%) of definite or probable ST (clopidogrel (n=2), prasugrel (n=4) and ticagrelor (n=5)) occurring at a median of 2 days after PCI. No specific predictors were found to be significantly associated with ST. New P2Y12 inhibitors were associated with more ST compared to clopidogrel (17.3% vs. 4.2%; respectively, p=0.05). ST was associated with a decreased left ventricular ejection fraction (p=0.007) and with a trend toward a higher mortality compared to patients without ST (82% vs. 52%, p=0.06).. The incidence of ST in OHCA survivors is high and associated with poor clinical outcome. The use of new oral P2Y12 inhibitors does not appear to be associated with a reduction in ST compared to clopidogrel.

Topics: Adenosine; Aspirin; Clopidogrel; Coma; Coronary Angiography; Coronary Thrombosis; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Out-of-Hospital Cardiac Arrest; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Retrospective Studies; Risk Factors; Stents; Ticagrelor; Ticlopidine; Treatment Outcome

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

Pre-hospital ticagrelor, given less than 1h before coronary intervention (PCI), failed to improve coronary reperfusion in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary PCI. It is unknown whether a longer interval from ticagrelor administration to primary PCI might reveal any improvement of coronary reperfusion.. We retrospectively compared 143 patients, pre-treated in spoke centers or ambulance with ticagrelor at least 1.5h before PCI (Pre-treatment Group), with 143 propensity score-matched controls treated with ticagrelor in the hub before primary PCI (Control Group) extracted from RENOVAMI, a large observational Italian registry of more than 1400 STEMI patients enrolled from Jan. 2012 to Oct. 2015 (ClinicalTrials.gov id: NCT01347580). The median time from ticagrelor administration and PCI was 2.08h (95% CI 1.66-2.84) in the Pre-treatment Group and 0.56h (95% CI 0.33-0.76) in the Control Group. TIMI flow grade before primary PCI in the infarct related artery was the primary endpoint.. The primary endpoint, baseline TIMI flow grade, was significantly higher in Pre-treatment Group (0.88±1.14 vs 0.53±0.86, P=0.02). However in-hospital mortality, in-hospital stent thrombosis, bleeding rates and other clinical and angiographic outcomes were similar in the two groups.. In a real world STEMI network, pre-treatment with ticagrelor in spoke hospitals or in ambulance loading at least 1.5h before primary PCI is safe and might improve pre-PCI coronary reperfusion, in comparison with ticagrelor administration immediately before PCI.

Topics: Adenosine; Aged; Ambulances; Chi-Square Distribution; Coronary Angiography; Coronary Thrombosis; Electrocardiography; Emergency Medical Services; Female; Hemorrhage; Hospital Mortality; Humans; Italy; Kaplan-Meier Estimate; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Propensity Score; Proportional Hazards Models; Registries; Retrospective Studies; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Stents; Ticagrelor; Time Factors; Time-to-Treatment; Transportation of Patients; Treatment Outcome

Drug-eluting bioresorbable vascular scaffold (BVS) is a revolutionary treatment option for obstructive coronary artery disease in percutaneous coronary intervention. It restores blood flow to the myocardium but unlike permanent metallic stent, BVS dissolves in the body within 2 years. This allows the coronary vessel to regain its normal function and motion. The clinical efficacy and safety of BVS in the first-in-human trials have been reported with low major adverse cardiac event rates observed at short- and long-term follow-up. The incidence of BVS scaffold thrombosis (ST) in these studies was 0 %. There is limited data on the incidence of BVS ST in the real world. We report 2 cases of subacute ST involving BVS in our real-world practice and discuss on the possible mechanisms of these thrombotic episodes (with insights from intracoronary imaging studies).

Topics: Absorbable Implants; Adenosine; Aged; Aspirin; Clopidogrel; Coronary Angiography; Coronary Stenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine; Treatment Outcome

We describe, to the best of our knowledge, the first incidence of stent thrombosis in a patient treated with ticagrelor, who exhibited high on-treatment platelet reactivity (HTPR) according to platelet reactivity testing. He was on clopidrogel and tested for platelet reactivity using the VerifyNow P2Y12 assay. The test showed a PRU of 249 and only 12% platelet inhibition. The patient was then switched to ticagrelor, with a loading dose of 180 mg given. The patient had stent thrombosis three weeks later with an acute myocardial infarction (MI). The patient had good platelet inhibition when started on Ticagrelor treatment (PRU=33), but had HTPR when the stent thrombosis occurred three weeks later (PRU=339).

Topics: Adenosine; Aged; Angina, Stable; Coronary Artery Disease; Coronary Thrombosis; Graft Occlusion, Vascular; Humans; Male; Myocardial Infarction; Platelet Aggregation Inhibitors; Stents; Ticagrelor

Topics: Adenosine; Clopidogrel; Coronary Thrombosis; Drug Resistance; Drug Substitution; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Function Tests; Predictive Value of Tests; Purpura, Thrombocytopenic, Idiopathic; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

Activation of coagulation and platelets is closely linked, and arterial thrombosis involves coagulation activation as well as platelet activation and aggregation. In these studies, we investigated the possible synergistic effects of rivaroxaban in combination with antiplatelet agents on thrombin generation and platelet aggregation in vitro and on arterial thrombosis and hemostasis in rat models.. Thrombin generation was measured by the Calibrated Automated Thrombogram method (0.5 pmol/L tissue factor) using human platelet-rich plasma (PRP) spiked with rivaroxaban (15, 30, or 60 ng/mL), ticagrelor (1.0 µg/mL), and acetylsalicylic acid (ASA; 100 µg/mL). Tissue factor-induced platelet aggregation was measured in PRP spiked with rivaroxaban (15 or 30 ng/mL), ticagrelor (1 or 3 µg/mL), or a combination of these. An arteriovenous (AV) shunt model in rats was used to determine the effects of rivaroxaban (0.01, 0.03, or 0.1 mg/kg), clopidogrel (1 mg/kg), ASA (3 mg/kg), and combinations on arterial thrombosis.. Rivaroxaban inhibited thrombin generation in a concentration-dependent manner and the effect was enhanced with ticagrelor and ticagrelor plus ASA. Rivaroxaban and ticagrelor also concentration-dependently inhibited tissue factor-induced platelet aggregation, and their combination increased the inhibition synergistically. In the AV shunt model, rivaroxaban dose-dependently reduced thrombus formation. Combining subefficacious or weakly efficacious doses of rivaroxaban with ASA or ASA plus clopidogrel increased the antithrombotic effect.. These data indicate that the combination of rivaroxaban with single or dual antiplatelet agents works synergistically to reduce platelet activation, which may in turn lead to the delayed/reduced formation of coagulation complexes and vice versa, thereby enhancing antithrombotic potency.

Topics: Adenosine; Adult; Animals; Arteriovenous Shunt, Surgical; Aspirin; Blood Coagulation; Clopidogrel; Coronary Thrombosis; Dose-Response Relationship, Drug; Female; Humans; Male; Platelet Activation; Platelet Aggregation Inhibitors; Rats; Rats, Wistar; Rivaroxaban; Thrombin; Ticagrelor; Ticlopidine

The choice of antiplatelet therapy after acute coronary syndrome (ACS) is complicated: Ticagrelor and prasugrel are novel alternatives to clopidogrel, patients with some genotypes may not respond to clopidogrel, and low-cost generic formulations of clopidogrel are available.. To determine the most cost-effective strategy for dual antiplatelet therapy after percutaneous coronary intervention for ACS.. Decision-analytic model.. Published literature, Medicare claims, and life tables.. Patients having percutaneous coronary intervention for ACS.. Lifetime.. Societal.. Five strategies were examined: generic clopidogrel, prasugrel, ticagrelor, and genotyping for polymorphisms of CYP2C19 with carriers of loss-of-function alleles receiving either ticagrelor (genotyping with ticagrelor) or prasugrel (genotyping with prasugrel) and noncarriers receiving clopidogrel.. Direct medical costs, quality-adjusted life years(QALYs), and incremental cost-effectiveness ratios (ICERs).. The clopidogrel strategy produced$179 301 in costs and 9.428 QALYs. Genotyping with prasugrel was superior to prasugrel alone, with an ICER of $35 800 per QALY relative to clopidogrel. Genotyping with ticagrelor was more effective than genotyping with prasugrel ($30 200 per QALY relative to clopidogrel). Ticagrelor was the most effective strategy($52 600 per QALY relative to genotyping with ticagrelor).. Stronger associations between genotype and thrombotic outcomes rendered ticagrelor substantially less cost-effective ($104 800 per QALY). Genotyping with prasugrel was the preferred therapy among patients who could not tolerate ticagrelor.. No randomized trials have directly compared genotyping strategies or prasugrel with ticagrelor.. Genotype-guided personalization may improve the cost-effectiveness of prasugrel and ticagrelor after percutaneous coronary intervention for ACS, but ticagrelor for all patients may bean economically reasonable alternative in some settings.

Topics: Acute Coronary Syndrome; Adenosine; Alleles; Aryl Hydrocarbon Hydroxylases; Clopidogrel; Coronary Thrombosis; Cost-Benefit Analysis; Cytochrome P-450 CYP2C19; Decision Support Techniques; Direct Service Costs; Drug Therapy, Combination; Drugs, Generic; Genotype; Hemorrhage; Humans; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Polymorphism, Genetic; Prasugrel Hydrochloride; Quality-Adjusted Life Years; Risk Factors; Thiophenes; Ticagrelor; Ticlopidine

Topics: Acute Coronary Syndrome; Adenosine; Clopidogrel; Coronary Angiography; Coronary Stenosis; Coronary Thrombosis; Coronary Vessels; Female; Humans; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Ticlopidine

Topics: Adenosine; Coronary Thrombosis; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Secondary Prevention; Thiophenes; Ticagrelor; Treatment Outcome

Topics: Adenosine; Angioplasty, Balloon, Coronary; Clopidogrel; Coronary Thrombosis; Decision Making; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticagrelor; Ticlopidine; Treatment Outcome

Despite the proven efficacy of dual antiplatelet therapy with aspirin and one of the first-generation P2Y(12) antagonists (clopidogrel, prasugrel) in patients with atherothrombotic disease, residual ischemic risk remains substantial, and bleeding rates are increased. Incomplete protection against ischemic events can be attributed to the fact that these therapies each target a single platelet activation pathway, allowing continued platelet activation via other pathways, including the protease-activated receptor-1 (PAR-1) pathway stimulated by thrombin. Increased bleeding with dual antiplatelet therapy can be attributed to blockade of the thromboxane A(2) (by aspirin) and adenosine diphosphate (by P2Y(12) antagonist) platelet activation pathways that are essential to hemostasis. The second-generation P2Y(12) inhibitor ticagrelor plus aspirin demonstrated superior ischemic outcomes, including reduction in total mortality, versus clopidogrel plus aspirin, but event rates remain high, and major bleeding not related to coronary artery bypass grafting is increased. The novel P2Y(12) antagonist elinogrel, available in intravenous and oral formulations, may have a more favorable benefit-to-risk profile than existing agents in this class because of reversible and competitive binding to the P2Y(12) receptor. Inhibition of PAR-1 is an attractive, novel approach in antiplatelet therapy because it may provide incremental ischemic protection without increasing bleeding. The PAR-1 antagonist vorapaxar (SCH 530348) has been associated with favorable efficacy and safety in phase 2 trials. Two phase 3 trials are evaluating the efficacy and safety of vorapaxar in patients presenting with non-ST-segment elevation acute coronary syndromes and in patients with documented atherothrombotic disease.

Topics: Acute Coronary Syndrome; Adenosine; Angioplasty, Balloon, Coronary; Aspirin; Clopidogrel; Coronary Artery Disease; Coronary Thrombosis; Drug Therapy, Combination; Humans; Lactones; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Pyridines; Quinazolinones; Randomized Controlled Trials as Topic; Receptor, PAR-1; Sulfonamides; Ticagrelor; Ticlopidine

Reperfusion therapy for myocardial infarction is limited by significant re-occlusion rates and less-than-optimal myocardial tissue perfusion. It was the objective of this study to assess and compare the effect of ticagrelor, the first reversibly binding oral P2Y12 receptor antagonist, with that of clopidogrel, in conjunction with thrombolytic therapy, on platelet aggregation, thrombus formation, and myocardial perfusion in a canine model. Thrombus formation was induced by electrolytic injury and blood flow was measured with a Doppler ultrasonic flowmeter. All animals received tissue plasminogen activator (tPA) (1 mg/kg over 20 min); 10 animals received clopidogrel (10 mg/kg IV bolus over 5 min), 10 animals received ticagrelor initiated with a 1-min bolus (75 microg/kg/min), followed by continuous infusion (10 microg/kg/min) for 2 h, and 10 animals received IV saline. Re-occlusion rate and cyclic flow variation decreased with ticagrelor compared to saline groups (p<0.05). Adenosine phosphate (ADP)-induced platelet aggregation decreased with ticagrelor (1.9% +/- 2.67) and clopidogrel (1.11% +/- 2.0) vs. saline (26.3% +/- 23.5, p<0.05) at the end of adjunctive therapy. Bleeding time increased in the clopidogrel compared to the ticagrelor group (p=0.01). Infarct size was reduced with ticagrelor compared to the clopidogrel and saline groups (p<0.05). Blood flow remained significantly below baseline values at 20 min after tPA administration in the saline and clopidogrel groups but not in the ticagrelor group. In conclusion, in a dog coronary thrombosis model, ticagrelor blocks ADP-induced platelet activation and aggregation; prevents platelet-mediated thrombosis; prolongs reperfusion time and reduces re-occlusion and cyclic flow variation; and significantly decreases infarct size and rapidly restores myocardial tissue perfusion.

Topics: Adenosine; Animals; Bleeding Time; Blood Coagulation; Clopidogrel; Coronary Circulation; Coronary Thrombosis; Disease Models, Animal; Dogs; Drug Therapy, Combination; Echocardiography; Female; Fibrinolytic Agents; Laser-Doppler Flowmetry; Male; Myocardial Infarction; Myocardial Reperfusion; Myocardium; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Recurrence; Thrombolytic Therapy; Ticagrelor; Ticlopidine; Time Factors; Tissue Plasminogen Activator

Topics: Adenosine; Clinical Trials as Topic; Clopidogrel; Coronary Thrombosis; Cost-Benefit Analysis; Hemorrhage; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prasugrel Hydrochloride; Prognosis; Purinergic P2 Receptor Antagonists; Pyridines; Risk Assessment; Survival Rate; Thiophenes; Ticagrelor; Ticlopidine; Treatment Outcome