ticagrelor and Coronary-Disease

Antiplatelet therapy is recommended among patients with established atherosclerosis. We compared monotherapy with a P2Y. In this systematic review and meta-analysis, all randomised trials comparing P2Y. A total of nine randomised trials were identified and included in this study, and 42 108 patients randomly allocated to a P2Y. Compared with aspirin monotherapy, P2Y. Italian Ministry of Education.

Topics: Aged; Aspirin; Atherosclerosis; Cerebrovascular Disorders; Clopidogrel; Coronary Disease; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Risk Assessment; Secondary Prevention; Stroke; Ticagrelor; Ticlopidine

The duration and combination of dual antiplatelet therapy after coronary stent implantation, consisting of aspirin and a P2Y12 inhibitor, is among the most intensely investigated therapeutic strategies in cardiovascular medicine. While initial studies have mainly focused on the efficacy and safety of individual antithrombotic agents, the increased need for a personalized, risk-based approach to define the optimal duration of antithrombotic treatment according to the estimated ischemic and bleeding risk was then recognized. Recent recommendations for the optimal duration of antithrombotic combination therapies following coronary stent implantation in various clinical scenarios have substantially changed. The aim of the present article is to discuss the recent evidence from randomized clinical trials and observational studies with respect to antithrombotic treatment regimens in patients undergoing coronary artery stenting for stable coronary artery disease (CAD) or an acute coronary syndrome (ACS). We will focus on optimal treatment duration and a personalized approach based on ischemic and bleeding risk assessment.

Topics: Acute Coronary Syndrome; Aspirin; Clopidogrel; Coronary Disease; Dose-Response Relationship, Drug; Drug Therapy, Combination; Hemorrhage; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Risk Factors; Stents; Ticagrelor

Whether ticagrelor is superior to prasugrel in inhibiting platelet reactivity (PR) has remained unclear, possibly because different test methods have been used to determine this. Therefore, using a different test method, we performed a meta-analysis comparing the effects of ticagrelor and prasugrel on PR.. PubMed, Embase, Web of Science, and Google Scholar were searched - without language restrictions (last updated on 26 February 2017) - for randomized trials comparing the effects of prasugrel with those of ticagrelor in patients with coronary artery disease. Selected studies were chosen for pooled analysis according to the inclusion and exclusion criteria. Data are presented as mean difference (MD) and 95% confidence interval. For the loading dose, using the VerifyNow-P2Y12 (VN) test, the PR was similar for both the prasugrel and ticagrelor groups [MD=10.80 (-9.81-31.40), P=0.30]. Using the vasodilatorstimulated phosphoprotein test, the PR was also similar for both the ticagrelor and prasugrel groups [MD=-2.87 (-6.35-0.60), P=0.10]. For the maintenance dose, using the VN test, the PR was lower in the ticagrelor group than in the prasugrel group [MD=-43.37 (-60.53 to -26.21), P<0.01]. Finally, using the vasodilator-stimulated phosphoprotein test, the PR was lower in the ticagrelor group than in the prasugrel group [MD=-9.23 (-15.82 to -2.64), P<0.01].. There was no difference between ticagrelor and prasugrel in terms of PR under the loading dose, but ticagrelor had a lower degree of PR under the maintenance dose. The results were not affected by the different PR test methods.

Topics: Adenosine; Adult; Aged; Blood Platelets; Cell Adhesion Molecules; Chi-Square Distribution; Coronary Disease; Female; Humans; Male; Microfilament Proteins; Middle Aged; Odds Ratio; Percutaneous Coronary Intervention; Phosphoproteins; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Risk Factors; Ticagrelor; Treatment Outcome

Topics: Absorbable Implants; Acute Coronary Syndrome; Adenosine; Aftercare; Aged, 80 and over; Cardiac Imaging Techniques; Coronary Angiography; Coronary Artery Bypass; Coronary Disease; Diabetic Angiopathies; Drug Therapy, Combination; Fibrinolytic Agents; Fractional Flow Reserve, Myocardial; Graft Occlusion, Vascular; Humans; Out-of-Hospital Cardiac Arrest; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prasugrel Hydrochloride; Prosthesis Design; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; ST Elevation Myocardial Infarction; Stents; Thrombectomy; Ticagrelor; Time-to-Treatment; Tissue Scaffolds

Topics: Acute Coronary Syndrome; Adenosine; Angioplasty, Balloon, Coronary; Aspirin; Clopidogrel; Coronary Disease; Drug Therapy, Combination; Early Medical Intervention; General Practice; Guideline Adherence; Humans; Male; Middle Aged; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Secondary Prevention; Stents; Thiophenes; Ticagrelor; Ticlopidine

The most common risks related to platelet inhibitor therapy are bleeding, drug-drug interactions and therapeutic failure. The new substances prasugrel and ticagrelor are more potent platelet inhibitiors than clopidogrel. This reduces the incidence of ischemic events, but also potentially increases the bleeding risk. Clopidogrel therapy has up to 20% non-response rates, which can partially be explained by genetic polymorphisms and drug-drug interactions. Currently no evidence exists that ticagrelor or prasugrel efficacy is affected by genetic polymorphisms. The therapy in patients at risk still has to be carefully adapted to minimize adverse events. Patients older than 75 years and/or weighing less than 60 kg should receive a reduced dose of prasugrel. The combination of ticagrelor with strong cytochrome-P450-3A4 inhibitors is contraindicated.. Blutungsereignisse, Arzneimittelwechselwirkungen und Therapieversagen sind relevante Risiken einer Therapie mit Plättchenaggregationshemmern. Die neuen Substanzen Prasugrel und Ticagrelor sind stärker wirksam als Clopidogrel und senken ischämische Ereignisse bei Patienten mit akutem Koronarsyndrom effizienter. Sie erhöhen allerdings potenziell auch die Blutungsraten. Eine Therapie mit Clopidogrel birgt das Risiko einer Therapieresistenz bei bis zu 20% der Patienten, die u. a. auf genetischen Polymorphismen und Arzneimittelinteraktionen beruht. Für Prasugrel und Ticagrelor bestehen keine Hinweise, dass genetische Polymorphismen die Wirksamkeit beeinflussen. In Risikosituationen muss die Therapie jedoch sorgfältig angepasst werden, um unerwünschte Wirkungen zu minimieren: So wird bei Patienten >75 Jahre und/oder einem Körpergewicht <60 kg aufgrund des erhöhten Blutungsrisikos eine Prasugrel-Dosisreduktion empfohlen. Ticagrelor ist in Kombination mit starken Cytochrom-P450–3A4-Hemmern kontraindiziert.. Les événements hémorragiques, les interactions médicamenteuses et l'échec de thérapie constituent les risques majeurs des traitements à base d'antiagrégants plaquettaires. Les substances nouvelles, prasugrel et ticagrelor, présentent un effet anitagrégant plus important et diminuent les épisodes ischémiques d'une manière plus efficacement que le clopidogrel. Cependent la possibilité existe d'une augmentation d'épisodes de saignement. Le risque de résistance à la thérapie atteint jusqu'à 20% pour les patients traités à base de clopidogrel, entre autre en raison de polymorphismes génétiques. Il n'existe pas d'evidence pour un mécanisme pareil pour le prasugrel et le ticagrelor. Dans certaines situations de risque par contre, une adaption du dosage est conseillée pour minimiser les effets secondaires négatifs: Chez les patients de plus de 75 ans, et/ou d'un poids corporel de moins de 60 kg, une réduction du dosage de prasugrel est conseillée en raison d'un risque élevé d'hémorragie. Il est contrindiqué d'utiliser ticagrelor en combinaison avec des inhibiteurs puissants du cytochrome-P450–3A4.

Topics: Adenosine; Angioplasty, Balloon, Coronary; Aspirin; Clopidogrel; Coronary Disease; Drug Interactions; Drug Resistance; Drug Therapy, Combination; Hemorrhage; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Risk Factors; Stents; Thiophenes; Ticagrelor; Ticlopidine

Patients commonly undergo noncardiac surgical procedures after implantation of a coronary stent. In the case where surgery cannot be deferred until completing the minimum duration of dual antiplatelet therapy, the Brigham and Women's Hospital Cardiac Catheterization Laboratory recommends using a glycoprotein IIb/IIIa bridging protocol to minimize the risk of perioperative ischemic events. We discuss our algorithm for managing antiplatelet agents, including the newer agents, prasugrel and ticagrelor, in patients undergoing noncardiac surgery after coronary stenting and present our glycoprotein IIb/IIIa bridging strategy along with a review of the relevant pharmacodynamic and clinical evidence.

Topics: Adenosine; Administration, Oral; Algorithms; Coronary Disease; Elective Surgical Procedures; Humans; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Practice Guidelines as Topic; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Risk Assessment; Risk Factors; Stents; Thiophenes; Ticagrelor

In the European Union Ticagrelor has recently been approved, as another P2Y12-receptor antagonist in addition to clopidogrel and prasugrel, in [corrected] the drug treatment after coronary intervention. [corrected] Dual antithrombotic treatment must be given for 4 weeks after elective implantation [corrected] of bare-metal stents, or for at least 6 months [corrected] with acetylsalicylic acid (ASA) plus clopidogrel after implantation of a drug-eluding stent. After an acute coronary syndrome ASA and clopidogrel (or prasugrel or ticagrelor) must be given for 12 months. In patients requiring urgent oral anticoagulation essential triple-drug treatment should be given over as short a [corrected] space of time if possible. [corrected] Prasugrel and ticagrelor may, to protect against gastroduodenal bleeding, be given without restriction together with a proton-pump inhibitor. Preoperative coagulation management is essential for patients who have been on dual platelet-aggregation inhibitors, but premature withdrawal of this medication should be avoided.

Topics: Adenosine; Aftercare; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Clopidogrel; Coronary Disease; Drug Administration Schedule; Drug Approval; Drug Therapy, Combination; Drug-Eluting Stents; Gastrointestinal Hemorrhage; Humans; Myocardial Revascularization; Piperazines; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prasugrel Hydrochloride; Proton Pump Inhibitors; Stents; Thiophenes; Ticagrelor; Ticlopidine

Topics: Adenosine; Angioplasty, Balloon, Coronary; Clinical Trials as Topic; Clopidogrel; Coronary Angiography; Coronary Disease; Coronary Occlusion; Coronary Restenosis; Drug-Eluting Stents; Foramen Ovale, Patent; Hospital Mortality; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prasugrel Hydrochloride; Purinergic P2 Receptor Antagonists; Radiology, Interventional; Thiophenes; Thrombolytic Therapy; Ticagrelor; Ticlopidine; Treatment Outcome

Three novel nonthienopyridine antiplatelet agents--cangrelor, ticagrelor (AZD6140), and SCH 530348--are in advanced clinical testing in patients with coronary artery disease. Cangrelor and ticagrelor are direct and reversible inhibitors of the platelet adenosine 5'-diphosphate P2Y12 receptor, whereas SCH 530348 is a thrombin receptor antagonist. Clinical data available to date for each of these compounds suggest that they have safety and efficacy profiles that will be advantageous to patients with acute coronary syndromes or undergoing percutaneous intervention. We review the clinical features of these new platelet inhibition therapies.

Topics: Acute Coronary Syndrome; Adenosine; Adenosine Monophosphate; Angioplasty, Balloon, Coronary; Aspirin; Clinical Trials as Topic; Coronary Disease; Drug Therapy, Combination; Humans; Lactones; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Antagonists; Pyridines; Receptors, Thrombin; 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

Oral antiplatelet therapy with P2Y(12) receptor blockers (especially clopidogrel) is the current choice of treatment during acute coronary syndromes and percutaneous interventions. To address the various limitations of thienopyridine therapy (including response variability and non-responsiveness) a novel drug, AZD6140, is under clinical development. AZD6140 is an oral and reversible P2Y(12) receptor blocker that does not require hepatic conversion to an active metabolite and produces an overall superior ADP-induced platelet inhibition with less response variability than clopidogrel. It has fast onset and offset actions that may be advantageous in patients who may have to undergo immediate surgery.

Topics: Adenosine; Animals; Coronary Disease; Drugs, Investigational; Humans; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Antagonists; Ticagrelor

Guidelines recommend that dual antiplatelet therapy using aspirin and clopidogrel should be administered to the majority of patients with acute coronary syndromes, including those undergoing percutaneous coronary intervention (PCI). However, the results of a large randomized, placebo-controlled study suggest that a 300-mg loading dose of clopidogrel must be administered at least 15 h prior to PCI in order to achieve a significant reduction in peri-PCI thrombotic events. Other data suggest that 2 h of pretreatment may be sufficient if a 600-mg loading dose is used. Since it is often difficult to achieve an adequate pretreatment goal with clopidogrel in clinical practice, more rapid achievement of platelet P2Y(12) inhibition may improve patient outcomes. Prasugrel, [6-[2-(3,4-diflurophenyl) cyclopropyl1-1-y1] amino-2-propylthio-9-D-ribofuranosyl-9H-purine (AZD6140), and cangrelor are platelet P2Y(12) receptor antagonists currently in development that offer faster acting inhibition of adenosine diphosphate (ADP)--induced platelet aggregation. These agents act upon the same platelet receptor as clopidogrel, but are distinguished by their routes of administration, reversibility, and pharmacodynamic properties. Prasugrel is an orally administered agent that provides faster, higher, and more consistent inhibition of platelet aggregation than clopidogrel. The results of Phase II testing suggest that the risk of bleeding is similar in prasugrel- and clopidogrel-treated patients. AZD6140 is another orally administered platelet inhibitor with rapid and reversible action. Again, Phase II testing suggests similar bleeding risk for clopidogrel. Preliminary evidence suggests that clinical outcomes may be better in prasugrel- and AZD6140-treated patients than in clopidogrel-treated patients. Cangrelor is an intravenously administered, reversible, short-acting agent with a rapid onset of activity. Bleeding risk and clinical outcomes data are similar in cangrelor- and abciximab-treated patients. The results of ongoing Phase III clinical trials involving more than 40,000 patients will demonstrate whether these agents fulfill their potential to improve outcomes in PCI-treated patients by providing faster, higher, and more consistent inhibition of platelet aggregation.

Topics: Adenosine; Angioplasty, Balloon, Coronary; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Clinical Trials as Topic; Clopidogrel; Coronary Disease; Dose-Response Relationship, Drug; Humans; Membrane Proteins; Myocardial Infarction; Platelet Aggregation; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Antagonists; Receptors, Purinergic P2Y12; Ticagrelor; Ticlopidine

ADP is one of the most important mediators of both physiologic hemostasis and thrombosis. Development and utilization of agents that block ADP receptors on the platelet membrane, namely thienopyridines, has represented a major advancement for treatment of patients undergoing percutaneous coronary interventions and those with acute coronary syndromes. Currently, clopidogrel, a second-generation thienopyridine that inhibits the ADP P2Y(12) receptor, represents the treatment of choice, in addition to aspirin, for the prevention of stent thrombosis. Further, long-term adjunctive use of this ADP P2Y(12) receptor antagonist is also associated with improved clinical outcomes in high-risk patients, and represents the standard of care for these patients. Despite the unambiguous clinical benefit associated with clopidogrel, accumulating experience with this drug has also led to identification of some of its drawbacks, which are related to inadequate platelet inhibition with standard dosage regimens as well as to its irreversible antiplatelet effects. This has led to the questioning of currently recommended clopidogrel dosage regimens as well as to the development of novel and more potent ADP P2Y(12) receptor antagonists, some of which are also reversible agents. Numerous studies are currently ongoing with the objective of demonstrating how more potent platelet inhibition using higher loading and maintenance dose regimens of clopidogrel or novel ADP P2Y(12) receptor antagonists - such as prasugrel, ticagrelor (AZD 6140) and cangrelor - will affect clinical outcomes. This article reviews the current knowledge of platelet ADP P2Y(12) receptor antagonism and the projected developments in this field.

Topics: Adenosine; Adenosine Monophosphate; Angioplasty, Balloon, Coronary; Blood Platelets; Clopidogrel; Coronary Disease; Humans; Membrane Proteins; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2 Receptor Antagonists; Receptors, Purinergic P2Y12; Thiophenes; Thrombosis; Ticagrelor; Ticlopidine

Monotherapy with a P2Y. In a double-blind trial, we examined the effect of ticagrelor alone as compared with ticagrelor plus aspirin with regard to clinically relevant bleeding among patients who were at high risk for bleeding or an ischemic event and had undergone PCI. After 3 months of treatment with ticagrelor plus aspirin, patients who had not had a major bleeding event or ischemic event continued to take ticagrelor and were randomly assigned to receive aspirin or placebo for 1 year. The primary end point was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. We also evaluated the composite end point of death from any cause, nonfatal myocardial infarction, or nonfatal stroke, using a noninferiority hypothesis with an absolute margin of 1.6 percentage points.. We enrolled 9006 patients, and 7119 underwent randomization after 3 months. Between randomization and 1 year, the incidence of the primary end point was 4.0% among patients randomly assigned to receive ticagrelor plus placebo and 7.1% among patients assigned to receive ticagrelor plus aspirin (hazard ratio, 0.56; 95% confidence interval [CI], 0.45 to 0.68; P<0.001). The difference in risk between the groups was similar for BARC type 3 or 5 bleeding (incidence, 1.0% among patients receiving ticagrelor plus placebo and 2.0% among patients receiving ticagrelor plus aspirin; hazard ratio, 0.49; 95% CI, 0.33 to 0.74). The incidence of death from any cause, nonfatal myocardial infarction, or nonfatal stroke was 3.9% in both groups (difference, -0.06 percentage points; 95% CI, -0.97 to 0.84; hazard ratio, 0.99; 95% CI, 0.78 to 1.25; P<0.001 for noninferiority).. Among high-risk patients who underwent PCI and completed 3 months of dual antiplatelet therapy, ticagrelor monotherapy was associated with a lower incidence of clinically relevant bleeding than ticagrelor plus aspirin, with no higher risk of death, myocardial infarction, or stroke. (Funded by AstraZeneca; TWILIGHT ClinicalTrials.gov number, NCT02270242.).

Topics: Aged; Aspirin; Coronary Disease; Double-Blind Method; Drug Therapy, Combination; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Mortality; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Factors; Stroke; Ticagrelor

Patients with type 2 diabetes mellitus (T2DM) are at higher risk of thrombotic complications. Studies have indicated that patients with T2DM have impaired clopidogrel-induced antiplatelet effect. Ticagrelor and prasugrel are two latest generation P2Y. This study, involving 140 patients with T2DM following percutaneous coronary intervention (PCI), evaluated the efficacy of aspirin upon concomitant use of prasugrel (10 mg/d) or ticagrelor (90 mg/d). Platelet reactivity was assessed by value of ADP-induced light transmittance aggregometry (LTA) and vasodilator-stimulated phosphoprotein phosphorylation-platelet reactivity index (VASP-PRI) at baseline, 7 and 30 days after randomized P2Y. Although ticagrelor and prasugrel have similar platelet inhibitory effects in patients with T2DM, if a P2Y

Topics: Adenosine; Aged; Aspirin; Coronary Disease; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Thrombosis; Ticagrelor; Time Factors

This randomized trial tested whether early loading with prasugrel can provide sufficient platelet inhibition even when given at the start of a 2-h infusion of cangrelor.. Effective platelet inhibition with intravenous cangrelor reduces the risk of ischemic complications during percutaneous coronary intervention (PCI). Transitioning to oral therapy with clopidogrel or prasugrel is only recommended after discontinuation of cangrelor due to drug interactions. Given the long half-life of prasugrel, this drug could achieve effective platelet inhibition even when given early under cangrelor and thereby prevent a transient gap in platelet inhibition.. This trial randomized 110 P2Y. The 3 groups were well balanced with respect to clinical parameters. One hour following discontinuation of cangrelor, the primary endpoint was seen in 65.0% of patients on clopidogrel versus 95.6% with ticagrelor and 93.3% with prasugrel (p for superiority of prasugrel vs. clopidogrel = 0.003; p of prasugrel vs. ticagrelor = 0.65). The 30-day incidence of ischemic and bleeding events was similar in all groups.. Prasugrel 60 mg given at the start of a 2-h infusion of cangrelor can provide a sufficient platelet inhibition post-cangrelor. This approach prevents the transient gap in platelet inhibition seen with oral loading after discontinuation of cangrelor. (Impact of Extent of Clopidogrel-Induced Platelet Inhibition during Elective Stent Implantation on Clinical Event Rate - Advanced Loading Strategies [ExcelsiorLOAD2]; DRKS00009739).

Topics: Adenosine; Adenosine Monophosphate; Administration, Oral; Aged; Blood Platelets; Clopidogrel; Coronary Disease; Drug Substitution; Female; Germany; Humans; Infusions, Intravenous; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Stents; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

Patients with diabetes appear to be at elevated risk of atherothrombotic events.. The purpose of this study was to determine the effect of antiplatelet therapy with ticagrelor on recurrent ischemic events in patients with diabetes and prior myocardial infarction (MI).. We examined the subgroups of patients with diabetes (n = 6,806) and without diabetes (n = 14,355) from PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction 54), in which 21,162 patients with a history of MI 1 to 3 years prior and with additional risk factors were randomized to ticagrelor (90 or 60 mg twice daily) or placebo. Patients were followed for a median of 33 months. The primary efficacy endpoint was major adverse cardiovascular events (MACE) (cardiovascular death, MI, stroke) and the primary safety endpoint was TIMI (Thrombolysis In Myocardial Infarction) major bleeding.. The relative risk reduction in MACE with ticagrelor was consistent for the pooled doses versus placebo in patients with diabetes (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.72 to 0.99; p = 0.035) and without diabetes (HR: 0.84; 95% CI: 0.74 to 0.96; p = 0.013; p interaction = 0.99). As patients with diabetes were at higher risk of MACE, the absolute risk reduction tended to be greater in patients with versus without diabetes (1.5% vs. 1.1%, with corresponding 3-year number needed to treat of 67 vs. 91). In patients with diabetes requiring pharmacological therapy (n = 5,960), the absolute risk reduction was 1.9% with a 3-year number needed to treat of 53. Additionally, in patients with diabetes, ticagrelor reduced cardiovascular death by 22% and coronary heart disease death by 34%. Similar to patients without diabetes, there was increased TIMI major bleeding in patients with diabetes (HR: 2.56; 95% CI: 1.52 to 4.33; p = 0.0004).. In patients with diabetes with prior MI, adding ticagrelor to aspirin significantly reduces the risk of recurrent ischemic events, including cardiovascular and coronary heart disease death. (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562).

Topics: Adenosine; Aged; Coronary Disease; Diabetes Mellitus; Dose-Response Relationship, Drug; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Secondary Prevention; Stroke; Ticagrelor

We prospectively assessed cardiac and pulmonary function in patients with stable coronary artery disease (CAD) treated with ticagrelor, clopidogrel, or placebo in the ONSET/OFFSET (A Multi-Centre Randomised, Double-Blind, Double-Dummy Parallel Group Study of the Onset and Offset of Antiplatelet Effects of AZD6140 Compared With Clopidogrel and Placebo With Aspirin as Background Therapy in Patients With Stable Coronary Artery Disease) study.. Ticagrelor reduces cardiovascular events more effectively than clopidogrel in patients with acute coronary syndromes. Dyspnea develops in some patients treated with ticagrelor, and it is not known whether this is associated with changes in cardiac or pulmonary function.. In all, 123 stable aspirin-treated CAD patients randomly received either ticagrelor (180 mg load, then 90 mg twice daily; n=57), clopidogrel (600 mg load, then 75 mg daily; n=54), or placebo (n=12) for 6 weeks in a double-blind, double-dummy design. Electrocardiography, echocardiography, serum N-terminal pro-brain natriuretic peptide, and pulmonary function tests were performed before (baseline) and 6 weeks after drug administration and/or after development of dyspnea.. After drug administration, dyspnea was reported by 38.6%, 9.3%, and 8.3% of patients in the ticagrelor, clopidogrel, and placebo groups, respectively (p<0.001). Most instances were mild and/or lasted<24 h, although 3 patients discontinued ticagrelor because of dyspnea. Eight of 22 and 17 of 22 ticagrelor-treated patients experiencing dyspnea did so within 24 h and 1 week, respectively, after drug administration. In all treatment groups, and in ticagrelor-treated patients with dyspnea, there were no significant changes between baseline and 6 weeks in any of the cardiac or pulmonary function parameters.. Dyspnea is commonly associated with ticagrelor therapy, but was not associated in this study with any adverse change in cardiac or pulmonary function. (A Multi-Centre Randomised, Double-Blind, Double-Dummy Parallel Group Study of the Onset and Offset of Antiplatelet Effects of AZD6140 Compared With Clopidogrel and Placebo With Aspirin as Background Therapy in Patients With Stable Coronary Artery Disease [ONSET/OFFSET]; NCT00528411).

Topics: Adenosine; Aged; Aspirin; Clopidogrel; Coronary Disease; Double-Blind Method; Dyspnea; Female; Heart; Humans; Lung; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Ticagrelor; Ticlopidine

This study aims to explore the clinical efficacy of ticagrelor combined with aspirin in patients with coronary heart disease angina pectoris and the effects on N terminal pro B type natriuretic peptide (NT-ProBNP) and creatine kinase-MB (CK-MB) levels.. A total of 150 patients with coronary heart disease angina pectoris were prospectively analyzed in this study. These patients were admitted to Huaiyin Hospital of Huai'an City from February 2017 to February 2019. The patients were divided into control group and research group according to different treatment methods. The following indicators before and after treatment were observed: therapeutic efficacy, prevalence of adverse reactions, duration and frequency of angina attack, NT-ProBNP and CK-MB levels. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of NT-ProBNP and CK-MB for the curative effect of coronary heart disease angina pectoris.. The total effective rate in the research group was higher than that in the control group (p<0.05). The prevalence of adverse reactions in the research group was lower than that in the control group (p<0.05). The duration and frequency of seizures of the two groups after treatment were lower than those before treatment. The duration and frequency of seizures in the research group were lower than those in the control group (p<0.05). The physiological function, physical pain, vital energy score and general health status in the research group were higher than those in the control group (p<0.05). The NT-ProBNP and CK-MB levels in both groups after treatment were decreased.. Ticagrelor combined with aspirin has definite therapeutic effect on patients with coronary heart disease angina pectoris, with low prevalence of adverse reactions. It can significantly reduce the levels of NT-ProBNP and CK-MB, which is worthy of promotion.

Topics: Adult; Aspirin; Coronary Disease; Creatine Kinase, MB Form; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Ticagrelor

Naoxintong Capsule (NXT), a Chinese medicine, has been widely used for the treatment of coronary heart disease (CHD) in clinics.. This study evaluated the cardioprotective effects of NXT alone and in combination with ticagrelor (TIC) and atorvastatin (ATO).. Qi deficiency and blood stasis rats were established by 8 weeks high fat diet feeding and 16 days exhaustive swimming and randomly divided into seven groups, that is, NXT (250, 500 and 1000 mg/kg/d), TIC (20 mg/kg/d), ATO (8 mg/kg/d), NXT (500 mg/kg/d)+TIC (20 mg/kg/d) and NXT (500 mg/kg/d)+ATO (8 mg/kg/d) group, with oral administration for 12 weeks. The contents of TC, TG, LDL-C, HDL-C, IL-1β, IL-6, IL-8, TNF-α, AST, ALT, SOD, MDA, CK-MB, LDH, TXA2, PGI2, IgA, IgG, IgM and C3 in serum were measured.. NXT + TIC group was significantly superior to the TIC group in decreasing the levels of TC (4.34 vs. 5.54), TG (3.37 vs. 4.66), LDL-C (1.21 vs. 1.35), LDH (4919.71vs. 5367.19) and elevating SOD level (248.54 vs. 192.04). NXT + ATO group was significantly superior to the ATO group in decreasing the levels of AST (195.931 vs. 241.63), ALT (71.26 vs. 83.16), LDH (4690.05 vs. 5285.82), TXA2 (133.73 vs. 158.67), IgG (8.08 vs. 9.80), C3 (2.03 vs. 2.35) and elevating the levels of HDL-C (1.19 vs. 0.91), SOD (241.91vs. 209.49).. The present findings demonstrate that the combined use of NXT with TIC and ATO had better integrated regulating effects than TIC and ATO, respectively. The mechanism of action requires further research.

Topics: Animals; Atorvastatin; Cardiotonic Agents; Coronary Disease; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Drugs, Chinese Herbal; Male; Qi; Rats; Rats, Sprague-Dawley; Ticagrelor

This study will assess the efficacy and safety of ticagrelor in the treatment of patients with stable coronary heart disease (SCHD).. We will search the following databases for relevant potential studies in Cochrane Library, MEDLINE, EMBASE, Web of Science, Google Scholar, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. We will search all literature sources from inception to the present without limitations of language and publication status. We will only consider randomized controlled trials on exploring the efficacy and safety of ticagrelor for the treatment of SCHD. Investigators will separately examine studies, collect data and appraise study quality. Data synthesis and analysis will be performed using RevMan 5.3 software.. This study will summarize high quality synthesis of present evidence of ticagrelor for the treatment of SCHD.. The findings of this study will provide evidence to appraise whether ticagrelor is effective for the treatment of patients with SCHD. OSF REGISTRATION NUMBER:: osf.io/fq69u.

Topics: Coronary Disease; Humans; Platelet Aggregation Inhibitors; Research Design; Systematic Reviews as Topic; Ticagrelor

Patients with acute coronary syndrome (ACS) and previous cardiovascular disease (CVD) (stroke, peripheral arterial disease [PAD] or coronary artery disease [CAD]) are at high risk of serious events and mortality. Current clinical guidelines recommend new antiplatelet drugs (NADs) for high cardiovascular risk patients with ACS; however, these drugs are underused in different scenarios.. This study included 1717 ACS patients from 3 tertiary hospitals. Of them, 641 (37.33%) suffered from previous CVD: 149 patients with stroke, 154 patients with PAD and 541 patients with CAD. Bleeding, mortality and major adverse cardiac events (MACE) at 1 year of follow-up after hospital discharge were analyzed.. NADs administration during hospital stay and at discharge was less frequent in patients with previous CVDs (P<0.001, for both). Cox analysis in this cohort of patients showed that clopidogrel prescription at discharge was independently associated with MACEs (HR: 1.59 [95% CI: 1.03-2.45]; P=0.036) and with death (HR: 1.99 [95% CI: 1.00-3.98]; P=0.049) in multivariate analysis. More specifically, when ticagrelor prescription at discharge was compared with clopidogrel, a significant death reduction was found in both, the univariate and the multivariate Cox analysis (HR: 4.54 [95% CI: 2.26-9.13]; P<0.001 and HR: 2.61 [95% CI: 1.16-5.90]; P=0.021, respectively).. New antiplatelet drugs, especially ticagrelor, showed lower rates of mortality in patients with CVD without differences for bleeding. Despite the recommendations of current clinical guidelines for high risk patients with ACS, the use of NADs is very low in "real-life" patients with previous CVD.

Topics: Acute Coronary Syndrome; Aftercare; Clopidogrel; Comorbidity; Coronary Disease; Drug Utilization; Female; Follow-Up Studies; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Metabolic Syndrome; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Proportional Hazards Models; Prospective Studies; Smoking; Spain; Stroke; Tertiary Care Centers; Ticagrelor

A single-center observational study was conducted in 1193 patients who underwent percutaneous coronary intervention and received DAPT after implementation of an algorithm that recommends. Implementing

Topics: Aged; Clinical Decision-Making; Clopidogrel; Coronary Disease; Cytochrome P-450 CYP2C19; Feasibility Studies; Female; Humans; Male; Middle Aged; North Carolina; Patient Selection; Percutaneous Coronary Intervention; Pharmacogenomic Testing; Pharmacogenomic Variants; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Predictive Value of Tests; Reproducibility of Results; Retrospective Studies; Risk Factors; Stents; Ticagrelor; Treatment Outcome

BACKGROUND In recent years, genetic factors have attracted research interest as important predisposing factors for cardiovascular susceptibility. This study aimed to investigate the influences of dual-dose clopidogrel, clopidogrel combined with tongxinluo, and ticagrelor on the platelet activity and MACE events of patients with CYP2C19*2 gene function deficiency and poor clopidogrel response after PCI. MATERIAL AND METHODS We selected 458 patients with coronary heart disease undergoing PCI, and the genotype of CYP2C19*2 was detected by TaqMan real-time PCR. We finally enrolled 212 patients and divided them into 4 groups: a standard anti-platelet group of 46 patients, a clopidogrel double-dose group of 50 cases, a clopidogrel combined with tongxinluo group of 59 cases, and a ticagrelor group of 57. The platelet inhibition rate was detected by TEG. We analyzed and compared differences in platelet activity and the occurrence of MACE events in these 4 groups at different follow-up times. RESULTS The results showed that inhibition of platelet aggregation was better in the double-dose clopidogrel group, the clopidogrel combined with tongxinluo group, and the ticagrelor group than in the regular-dose clopidogrel group, and ticagrelor was the best. We also found that the total incidence of MACE was much lower in the double-dose clopidogrel group, the clopidogrel combined with tongxinluo group, and the ticagrelor group, while the incidence of hemorrhage in the ticagrelor group was higher. CONCLUSIONS Adjusting the dose or combining with other drugs improves the efficacy of anti-platelet therapy and reduces the incidence of ischemic events after PCI.

Topics: Adenosine; Aged; Blood Platelets; Clopidogrel; Coronary Disease; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C19 Inhibitors; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Humans; Male; Middle Aged; Mutation; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Ticlopidine

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

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

Topics: Adenosine; Coronary Disease; Humans; Long-Term Care; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Recurrence; Ticagrelor

Antiplatelet therapy has established clinical benefit on cardiovascular outcome and has reduced the rates of re-infarction/in stent thrombosis following percutaneous coronary intervention in acute coronary syndromes. Major bleeding episodes can occur with antiplatelet therapy and intracranial hemorrhage (ICH) is one of the most feared complications resulting in significant morbidity and mortality. Identification of high risk groups and judicious use of antiplatelet therapy reduces the bleeding risk. Ticagrelor is a newer P2Y12 receptor antagonist with established clinical benefit. However, risks of having an ICH with these newer molecules cannot be ignored. Here, we report a case of spontaneous acute subdural hematoma developing in a patient on antiplatelet therapy with aspirin and ticagrelor. Early recognition, discontinuation of the medication and appropriate management resulted in resolution of hematoma and good clinical outcome. Authors have reviewed the antithrombotic drugs and their tendencies in causing intracranial bleeds from a neurophysicians perspective.

Topics: Adenosine; Biomarkers; Combined Modality Therapy; Coronary Disease; Diagnosis, Differential; Drug Therapy, Combination; Echocardiography; Electrocardiography; Hematoma, Subdural; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Purinergic P2Y Receptor Antagonists; Stents; Ticagrelor; Tomography, X-Ray Computed

Topics: Adenosine; Aftercare; Angioplasty, Balloon, Coronary; Coronary Disease; Follow-Up Studies; Humans; Myocardial Revascularization; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Recurrence; Retreatment; Risk Factors; Stents; Survival Rate; Thiophenes; Ticagrelor

Topics: Acute Coronary Syndrome; Adenosine; Aspirin; Clopidogrel; Coronary Disease; Coronary Restenosis; Drug-Eluting Stents; Electrocardiography; Female; Humans; Male; Platelet Aggregation Inhibitors; Ticagrelor; Ticlopidine

Topics: Adenosine; Aryl Hydrocarbon Hydroxylases; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Coronary Disease; Cytochrome P-450 CYP2C19; Humans; Polymorphism, Genetic; Purinergic P2Y Receptor Antagonists; Ticagrelor

Topics: Adenosine; Clinical Trials as Topic; Coronary Disease; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Risk Factors; Ticagrelor