ticagrelor and Angina--Unstable

Dual antiplatelet therapy is the cornerstone of maintenance medication following invasive treatment of patients with acute coronary syndromes (ST elevation myocardial infarction, non-ST elevation myocardial infarction, unstable angina). Over the last decade, P2Y12 inhibition in addition to low-dose acetylsalicylic acid has been intensively debated. The debate was enriched by the results of the large phase III clinical trials for prasugrel (TRITON) and ticagrelor (PLATO) compared to clopidogrel in patients with acute coronary syndromes. This article summarizes the critical details und subanalyses of both study programmes and highlights on clinical decision making when using the three P2Y12 blockers in acute coronary syndromes. A special focus is on higher risk patients such as those with ST elevation myocardial infarction and those with coexisting diabetes, but also on minimizing relevant bleedings, which are common during more intense platelet inhibition.

Topics: Acute Coronary Syndrome; Adenosine; Angina, Unstable; Aspirin; Blood Platelets; Clopidogrel; Hemorrhage; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Platelet Transfusion; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticagrelor; Ticlopidine

Non-ST elevation acute coronary syndromes are responsible for approximately 1 million admissions to U.S. hospitals and twice as many to European hospitals each year. Thus, they are among the most common serious illnesses in adults, and are associated with an in-hospital mortality of approximately 5%. The most common cause is rupture of an atherosclerotic coronary plaque, resulting in subtotal coronary occlusion. Diagnosis is based on the clinical picture of retrosternal chest pain, aided by electrocardiographic findings of ST segment deviations and biomarker abnormalities (elevation of troponin and natriuretic peptides) and cardiac imaging (myocardial scans showing perfusion defects). Treatment involves antiischemic agents (nitrates and β blockers), antiplatelet drugs (aspirin, P2Y(12), and glycoprotein IIb/IIIa receptor blockers), and anticoagulants (unfractionated and low-molecular-weight heparins). Patients should undergo risk stratification, and those with high-risk factors should undergo coronary arteriography promptly with the intent to carry out coronary revascularization. Those at low risk should continue to receive intensive antiischemic and antithrombotic therapy. At discharge, patients should receive intensive lipid-lowering therapy with high doses of a statin, as tolerated.

Topics: Acute Coronary Syndrome; Adenosine; Angina, Unstable; Anticoagulants; Aspirin; Clopidogrel; Coronary Angiography; Echocardiography; Electrocardiography; Humans; Myocardial Infarction; Myocardial Revascularization; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Risk Factors; Thiophenes; Ticagrelor; Ticlopidine

Topics: Adenosine; Angina, Unstable; Anticoagulants; Blood Glucose; Guideline Adherence; Humans; Kidney Failure, Chronic; Myocardial Infarction; Patient Education as Topic; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Practice Guidelines as Topic; Prasugrel Hydrochloride; Proton Pump Inhibitors; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticagrelor

This focused update addresses the use of the newly approved oral antiplatelet agents, prasugrel and ticagrelor, for the management of patients with UA/NSTEMI.

Topics: Adenosine; Administration, Oral; Angina, Unstable; Anticoagulants; Evidence-Based Medicine; Hemorrhage; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Risk Assessment; Risk Factors; Thiophenes; Ticagrelor; Treatment Outcome; Warfarin

Acute coronary syndromes reflect a spectrum of disease related, most commonly, to the sudden reduction in blood flow to a portion of myocardium. The underlying pathogenesis of the reduction in coronary flow is related to the sudden rupture of an atherosclerotic plaque, with subsequent thrombus formation leading to either vascular occlusion or microembolization. Clinicians combat this process with antithrombotic therapy, which typically includes both anticoagulant and antiplatelet therapy, and mechanical therapies, such as percutaneous coronary interventions, nearly always using stents. This review focuses on P2Y12 antagonists as one component of our armamentarium of antiplatelet therapies, specifically on data addressing in whom, when, which agent, and in what dose such agents should be administered.

Topics: Acute Coronary Syndrome; Adenosine; Angina, Unstable; Aspirin; Humans; Integrin alpha2; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; 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

Platelets play a central role in the pathophysiology of acute coronary syndromes (ACS). Dual antiplatelet therapy has resulted in significant advances in the treatment of ACS; however, ACS remains an important cause of morbidity and mortality. Important limitations exist among the current antiplatelet agents and therefore a pressing need for the development of improved antiplatelet agents exists. Three antiplatelet agents currently under investigation (prasugrel, AZD6140, and cangrelor) in clinical trials for the treatment of ACS appear promising.

Topics: Adenosine; Adenosine Monophosphate; Angina, Unstable; Blood Platelets; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Thiophenes; Ticagrelor; Treatment Outcome

Topics: Angina, Unstable; Carbidopa; Drug Combinations; Humans; Levodopa; Methane; Methoxyflurane; Randomized Controlled Trials as Topic; Ticagrelor

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

Topics: Acute Coronary Syndrome; Adenosine; Aged; Angina, Unstable; Blood Platelets; Cells, Cultured; Drug Interactions; Female; Humans; Intestinal Absorption; Male; Metoclopramide; Middle Aged; Morphine; Platelet Activation; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor

Oral administration of crushed ticagrelor tablets turned out to be an efficacious method that improves its pharmacokinetics and pharmacodynamics. This strategy, however, is unlikely to eliminate the drug-drug interaction in patients receiving intravenous morphine, as the impairment of the P2Y12 inhibitor absorption related to decreased propulsive motility of the gastro-intestinal tract is the most likely mechanism of interaction. Thus, we designed a pharmacokinetic and pharmacodynamic study setting the feasibility of platelet inhibition with a loading dose of ticagrelor given as crushed tablets sublingually compared with two other ticagrelor loading dose administration strategies: integral tablet given orally and crushed tablet given orally in patients with unstable angina. Ticagrelor and its metabolite AR-C124900XX plasma concentration was evaluated in nine time points (time frame of 6 hours) using liquid chromatography coupled with mass spectrometry; platelet reactivity was evaluated using multiple electrode aggregometry. The area under the plasma concentration-time curve for ticagrelor and AR-C124900XX was significantly higher in patients treated with crushed tablets given orally compared with crushed tablets given sublingually only within the first hour after loading dose (936.9 ± 898.0 vs 368.0 ± 422.4, p=0.042 and 103.4 ± 120.8 vs 31.3 ± 43.9, p=0.031, respectively). Moreover, we showed significantly stronger platelet inhibition in patients receiving crushed ticagrelor orally vs. sublingually at 30 and 45 min after the loading dose (p=0.024 and p=0.016, respectively). Therefore, the administration strategy of ticagrelor determines the pharmacokinetic and pharmacodynamic profile of both ticagrelor and its active metabolite AR-C124900XX.

Topics: Activation, Metabolic; Adenosine; Administration, Sublingual; Aged; Angina, Unstable; Area Under Curve; Drug Compounding; Feasibility Studies; Female; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors; Poland; Powders; Purinergic P1 Receptor Agonists; Tablets; Ticagrelor; Treatment Outcome

This study aims to compare the effects of ticagrelor and clopidogrel on platelet function, cardiovascular prognosis, and bleeding in patients with unstable angina pectoris.. Patients with unstable angina pectoris undergoing percutaneous coronary intervention (PCI) were enrolled (January 2018-December 2019). In total, 212 patients were treated with ticagrelor (90 mg twice daily) and 210 patients were treated with clopidogrel (75 mg once daily). Thromboelastography and light transmission aggregometry were used to measure the platelet aggregation rate (PAR). High-sensitivity troponin T (hs-TnT), pro-brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (CRP), and heart-type fatty acid-binding protein (h-FABP) were measured to assess myocardial injury after PCI. Cardiovascular prognosis and bleeding events were evaluated in hospital and 12 months after discharge.. The PAR was significantly slower with ticagrelor (P < 0.001). hs-TnT, NT-proBNP, CRP, and h-FABP increased after compared with before PCI in both groups (P < 0.05). hs-TnT (P < 0.001) and h-FABP (P < 0.001) increased more significantly with clopidogrel. The in-hospital and 12-month major adverse cardiovascular event (MACE) rates were not significantly different between the two groups. The in-hospital total bleeding event rate was higher with ticagrelor (P < 0.05). Minor bleeding and total bleeding were more frequent at the 12-month follow-up in the ticagrelor group (P < 0.05).. Ticagrelor was more effective in suppressing the PAR than clopidogrel and reduced PCI-induced myocardial injury in patients with unstable angina pectoris. However, it increased in-hospital and 12-month bleeding events and had no benefit on in-hospital and 12-month MACEs.

Topics: Angina, Unstable; Clopidogrel; Fatty Acid Binding Protein 3; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prognosis; Ticagrelor; Treatment Outcome

 This article compares the clinical outcomes of clopidogrel and ticagrelor in patients with acute coronary syndrome (ACS) without cytochrome P450 (CYP)2C19 loss-of-function (LOF) alleles and investigates whether clopidogrel could be an alternative P2Y12 inhibitor without increasing the risk of ischemic events..  Patients were divided into the clopidogrel-treated group and the ticagrelor-treated group. Inverse probability of treatment weighting (IPTW) calculated by propensity scores was used to adjust confounding covariates. The primary outcome was major adverse cardiovascular or cerebrovascular events (MACCEs) within 12 months. The secondary outcomes were MACCEs plus unstable angina, and clinically significant bleeding events..  Finally, 2,199 patients were included. Of them, 1,606 were treated with clopidogrel, and 593 were treated with ticagrelor. The mean age of the original cohort was 59.92 ± 9.81 years. During the 12-month follow-up period, MACCEs occurred in 89 patients (4.0%). No significant differences were observed in MACCEs (IPTW-adjusted hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.65-1.18), MACCEs plus unstable angina (IPTW-adjusted HR, 1.20; 95% CI, 0.91-1.59), or clinically significant bleeding events (IPTW-adjusted HR, 0.81; 95% CI, 0.53-1.23) between the clopidogrel- and ticagrelor-treated groups..  In patients with ACS without CYP2C19 LOF alleles, clopidogrel was not associated with a higher risk of MACCEs when compared with ticagrelor. The main findings of this study support use of clopidogrel in CYP2C19 LOF noncarriers as an alternative P2Y12 inhibitor, which may reduce medical expenses and adverse reactions caused by more potent P2Y12 inhibitors in these patients.

Topics: Acute Coronary Syndrome; Aged; Alleles; Angina, Unstable; Clopidogrel; Cytochrome P-450 CYP2C19; Hemorrhage; Humans; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

Topics: Acute Coronary Syndrome; Angina, Unstable; Aspirin; Cardiac Rehabilitation; Clopidogrel; Combined Modality Therapy; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prasugrel Hydrochloride; Secondary Prevention; ST Elevation Myocardial Infarction; Ticagrelor; United Kingdom

Major adverse cardiac event (MACE) and bleeding risks following percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS) are not well defined in individuals with heart failure (HF). We followed 1,145 individuals in the Pharmacogenomic Resource to improve Medication Effectiveness Genotype Guided Antiplatelet Therapy cohort for MACE and bleeding events following PCI for ACS. We constructed Cox proportional hazards models to compare MACE and bleeding in those with versus without HF, adjusting for sociodemographics, comorbidities, and medications. We also determined predictors of MACE and bleeding events in both groups. 370 (32%) individuals did and 775 (68%) did not have HF prior to PCI. Mean age was 61.7 ± 12.2 years, 31% were female, and 24% were African American. After a median follow-up of 0.78 years, individuals with HF had higher rates of MACE compared to those without HF (48 vs. 24 events per 100 person years) which remained significant after multivariable adjustment (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.00 to 1.72). Similarly, bleeding was higher in those with versus without HF (22 vs. 11 events per 100 person years), although this was no longer statistically significant after multivariable adjustment (HR 1.29, 95% CI 0.86 to 1.93). Diabetes and peripheral vascular disease were predictors of MACE, and end-stage renal disease was a predictor of bleeding among participants with HF. MACE risk is higher in individuals with versus without HF following PCI for ACS. However, the risk of bleeding, especially among those with end-stage renal disease , must be considered when determining post-PCI anticoagulant strategies.

Topics: Acute Coronary Syndrome; Aged; Angina, Unstable; Aspirin; Case-Control Studies; Clopidogrel; Diabetes Mellitus; Dual Anti-Platelet Therapy; Female; Heart Failure; Hemorrhage; Hospitalization; Humans; Ischemic Attack, Transient; Ischemic Stroke; Kidney Failure, Chronic; Male; Middle Aged; Mortality; Multivariate Analysis; Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Percutaneous Coronary Intervention; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Proportional Hazards Models; Risk Factors; ST Elevation Myocardial Infarction; Stroke Volume; Ticagrelor; Treatment Outcome

To investigate the effect of ticagrelor combined with tirofiban versus clopidogrel combined with tirofiban on inflammation response and prognosis of patients with unstable angina pectoris (UA). The present prospective study included a total of 291 patients who were diagnosed as unstable UA from January 2018 to December 2019. All UA patients were divided into two groups: ticagrelor combined with tirofiban group (n = 159) and clopidogrel combined with tirofiban group (n = 132). Serum levels of C-reactive protein (CRP), interleukin-1β, interleukin-6, tumor necrosis factor-α, and matrix metalloproteinase-9 were measured using commercially available enzyme-linked immunosorbent assay kits. Kaplan-Meier (K-M) curve was performed for analysis of cumulative incidences of major adverse cardiovascular events (MACEs). Both ticagrelor combined with tirofiban and clopidogrel combined with tirofiban significantly decreased the serum levels of inflammatory factors in UA patients. Compared to clopidogrel combined with the tirofiban group, ticagrelor combined with the tirofiban group had a lower platelet aggregation rate and improved cardiac function of UA patients. Besides, ticagrelor combined with tirofiban group had a better prognosis and the K-M curve showed that UA patients treated by ticagrelor and tirofiban had lower incidences of MACEs in one-year follow-up. The treatment of ticagrelor combined with tirofiban significantly attenuated inflammation response and improved the prognosis of UA patients.

Topics: Aged; Angina, Unstable; Biomarkers; C-Reactive Protein; Clopidogrel; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Kaplan-Meier Estimate; Male; Matrix Metalloproteinase 9; Middle Aged; Platelet Aggregation Inhibitors; Prognosis; Prospective Studies; Ticagrelor; Tirofiban; Tumor Necrosis Factor-alpha

Bleeding risk stratification is an unresolved issue in older adults. Anemia may reflect subclinical blood losses that can be exacerbated after percutaneous coronary intervention . We sought to prospectively determine the contribution of anemia to the risk of bleeding in 448 consecutive patients aged 75 or more years, treated by percutaneous coronary interventions without concomitant indication for oral anticoagulation. We evaluated the effect of WHO-defined anemia on the incidence of 1-year nonaccess site-related major bleeding. The prevalence of anemia was 39%, and 13.1% of anemic and 5.2% of nonanemic patients suffered a bleeding event (hazard ratio 2.75, 95% confidence interval 1.37 to 5.54, p = 0.004). Neither PRECISE-DAPT nor CRUSADE scores were superior to hemoglobin for the prediction of bleeding. In conclusion, anemia is a powerful predictor of bleeding with potential utility for simplifying tailoring therapies.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Anemia; Angina, Unstable; Anticoagulants; Antithrombins; Aspirin; Cause of Death; Clopidogrel; Comorbidity; Coronary Artery Disease; Drug-Eluting Stents; Female; Gastrointestinal Hemorrhage; Hemorrhage; Heparin; Hirudins; Humans; Intracranial Hemorrhages; Kaplan-Meier Estimate; Male; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Care; Postoperative Hemorrhage; Prasugrel Hydrochloride; Proportional Hazards Models; Prospective Studies; Recombinant Proteins; Risk Assessment; Stents; Ticagrelor; Urologic Diseases

Background Prior reports indicate that the effect of P2Y

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

Topics: Adult; Angina, Unstable; Electrocardiography; Factor Xa Inhibitors; Female; Fondaparinux; Heart Arrest; Humans; Platelet Aggregation Inhibitors; Ticagrelor

Topics: Adenosine; Aged; Angina, Unstable; Atrial Fibrillation; Clopidogrel; Humans; Male; Ticagrelor; Ticlopidine; Treatment Outcome

Topics: Adenosine; Aged; Aged, 80 and over; Angina, Unstable; Cost-Benefit Analysis; Drug Costs; England; Guideline Adherence; Humans; Life Expectancy; Models, Economic; Myocardial Infarction; Practice Guidelines as Topic; Purinergic P2Y Receptor Antagonists; Ticagrelor

Topics: Adenosine; Angina, Unstable; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Thrombosis; Ticagrelor