prasugrel-hydrochloride and Atrial-Fibrillation

The optimal antithrombotic strategy for patients with a long-term indication for anticoagulation and acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) remains controversial. This meta-analysis aims to compare randomised trials' outcomes of these patients, focussing on dual versus triple antithrombotic and non vitamin K oral anticoagulants (NOACs) versus vitamin K oral anticoagulants regimens.. Medline, Embase and Cochrane databases were searched from January 1980 to March 2019 yielding 309 articles, and after careful screening, five randomized trials totalling 10 643 patients were included for analysis.. Dual antithrombotic regimens were associated with significantly less thrombolysis in myocardial infarction (TIMI) major and minor bleeding [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.40-0.71], with no significant difference in major adverse cardiovascular events (OR 0.93, 95% CI 0.72-1.22) or all-cause mortality (OR 0.89, 95% CI 0.61-1.19). NOAC regimens had significantly lower TIMI major and minor bleeding (OR 0.58, 95% CI 0.43-0.78) and intracranial bleeding (OR 0.33, 95% CI 0.16-0.66), with similar rates of major adverse cardiovascular events (OR 1.00, 95% CI 0.86-1.16) and all-cause mortality (OR 1.01, 95% CI 0.81-1.26).. Dual antithrombotic and NOAC regimens have reduced bleeding without compromising the risk of cardiovascular events or mortality, and should be preferred for patients with ACS or PCI also needing long-term anticoagulation.

Topics: Acute Coronary Syndrome; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Dabigatran; Drug Therapy, Combination; Dual Anti-Platelet Therapy; Factor Xa Inhibitors; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Ticagrelor; Warfarin

Topics: Acute Coronary Syndrome; Adenosine; Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Hemorrhage; Humans; Morpholines; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Postoperative Complications; Prasugrel Hydrochloride; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Thrombosis; Ticagrelor

Strategies to prevent stroke recurrences and stroke-related morbidity and mortality are a major concern for healthcare systems worldwide. Antithrombotic therapy is the cornerstone for the secondary prevention of ischemic stroke.. This article is an overview of currently used antithrombotic therapies in the management of ischaemic stroke with special focus on their pharmacokinetic properties and how these properties may influence their clinical utility. This review covers both antiplatelet drugs and antitcoagulants used in the primary and secondary prevention of ischaemic stroke.. The role of aspirin in the early management of stroke is well established. Furthermore, antiplatelet drugs (aspirin, aspirin/dypiridamol and clopidogrel) are the cornerstone of secondary prevention of ischaemic stroke, while their role in the primary prevention is less well established. There are limited data on the use of novel antiplatelet agents for the management of stroke patients. Anticoagulation has not been associated with clinical benefits when used early in the management of acute ischaemic stroke. Long-term therapy with vitamin K antagonists provides prognostic benefit in patients with atrial fibrillation and additional stroke risk factors. New oral anticoagulants have demonstrated at least similar efficacy with vitamin K anatagonists in preventing stroke in patients with atrial fibrillation.

Topics: Administration, Oral; Anticoagulants; Aspirin; Atrial Fibrillation; Cilostazol; Clopidogrel; Factor Xa; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Risk Factors; Stroke; Tetrazoles; Thiophenes; Thrombin; Ticlopidine; Vitamin K

The use of triple therapy (warfarin plus dual antiplatelet therapy) has increased in recent years due to an aging population with a higher risk for atrial fibrillation, as well as the increased use of coronary stents for acute coronary syndromes. Triple therapy confers a higher bleeding risk than either warfarin or dual antiplatelet therapy alone. However, warfarin alone is inadequate for patients with indications for triple therapy because of an unacceptable risk of stent thrombosis, and dual antiplatelet therapy is inferior to warfarin for the prevention of ischemic strokes in patients with atrial fibrillation, mechanical valves, or intraventricular thrombosis. Hospitalists face the challenge of balancing the aforementioned risks; the optimal management of these patients requires knowledge of the relevant literature and expertise. In this paper, we review the current literature on antiplatelet and anticoagulant combinations in patients with atrial fibrillation and coronary stents in order to improve adherence to published guidelines and to reduce the risk of bleeding.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Drug Therapy, Combination; Drug-Eluting Stents; Hospitalization; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Thiophenes; Ticlopidine; Warfarin

In the AFIRE trial, rivaroxaban monotherapy was noninferior to combination therapy with rivaroxaban and an antiplatelet agent for thromboembolic events or death, and superior for major bleeding in patients with atrial fibrillation (AF) and stable coronary artery disease. Little is known about impacts of stroke and bleeding risks on the efficacy and safety of rivaroxaban monotherapy.. In this subanalysis of the AFIRE trial, we assessed the risk of stroke and bleeding by the CHADS. Rivaroxaban monotherapy significantly reduced the primary efficacy and safety end points with no evidence of differential effects by stroke risk (CHADS. The advantages of rivaroxaban monotherapy compared with those of combination therapy with respect to all prespecified end points, including thromboembolism, bleeding, and mortality were similar across patients with AF and stable coronary artery disease, irrespective of their risk for stroke and bleeding.. UMIN Clinical Trials Registry number, UMIN000016612, and ClinicalTrials.gov number, NCT02642419.

Topics: Aged; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Outcome and Process Assessment, Health Care; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Risk Adjustment; Rivaroxaban; Stroke

Using the standard maintenance dose of prasugrel (10 mg/day) as part of triple therapy with aspirin and an oral anticoagulant (OAC) is not recommended in the current guidelines because it increases the risk of bleeding compared with clopidogrel. However, the safety and efficacy of low-dose prasugrel (3.75 mg/day) as part of triple therapy has not been reported. Methods and Results: We registered 816 consecutive patients with atrial fibrillation (AF) who underwent percutaneous coronary intervention (PCI) from January 2011 to June 2016 at 8 hospitals in Japan. We examined the clinical outcomes of patients who received either low-dose prasugrel (n=57) or clopidogrel (n=451) as part of triple therapy after PCI. The incidences of bleeding (TIMI major and minor) and major adverse cerebrocardiovascular events (MACCE; all-cause death, nonfatal myocardial infarction, stent thrombosis, unplanned revascularization, and stroke) were evaluated. The cumulative 1-year incidence of bleeding was not significantly different (prasugrel 5.6% vs. clopidogrel 8.1%, log-rank P=0.55). In addition, the cumulative 1-year incidence of MACCE was also not significantly different (prasugrel 11.5% vs. clopidogrel 12.3%, log-rank P=0.88).. Low-dose prasugrel, as part of triple therapy, did not increase the risk of bleeding compared with clopidogrel. Therefore, it can be an alternative to clopidogrel for patients with AF undergoing PCI.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Registries

Patients with atrial fibrillation who undergo coronary stenting require triple antithrombotic therapy, including aspirin, a P2Y. We hypothesized that 1-month P2Y. SAFE-A (UMIN Clinical Trials Registry Number: UMIN000015923) is a multicenter, prospective, randomized, open-label, blinded-endpoint, parallel-group, comparative study that was designed to compare the safety and efficacy of short-duration treatment with a P2Y. The SAFE-A study is the first randomized controlled trial to compare 1-month vs. 6-month P2Y

Topics: Aspirin; Atrial Fibrillation; Blood Transfusion; Clopidogrel; Drug Therapy, Combination; Drug-Eluting Stents; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Pyrazoles; Pyridones; Stroke; Ticlopidine

Associations between atrial fibrillation (AF), outcomes, and response to antiplatelet therapies in patients with acute coronary syndrome (ACS) managed medically without revascularization remain uncertain. We examined these associations for medically managed ACS patients randomized to dual antiplatelet therapy (DAPT) using patient data from the TRILOGY ACS trial. DAPT included aspirin plus clopidogrel 75 mg/d or prasugrel 10 mg/d (5 mg/d for those <60 kg or age ≥75 years). Patients receiving oral anticoagulants were excluded. Cox proportional hazards regression modeling was used to characterize associations between patients with AF (AF+) vs those without (AF-) and risk of ischemic and bleeding events, and to explore effects of randomized treatment on outcomes. Among 9101 patients with baseline AF status, 710 (7.8%) had AF. AF+ patients were older and had more comorbidities. Unadjusted associations of the composite of cardiovascular death/myocardial infarction/stroke were significantly higher among AF patients at 30 months (31.1% vs 18.4%; HR: 1.61, 95% CI: 1.35-1.92, P < 0.001), but differences did not persist after adjustment (HR: 1.16, 95% CI: 0.97-1.39, P = 0.11). When individual components of the composite endpoint were evaluated, 30-month risk of events in AF+ patients was significantly higher. Thirty-month risk of all-cause death was significantly higher in AF+ patients: 18.1% vs 11.1% (HR: 1.62, 95% CI: 1.30-2.02, P < 0.001). There was no significant interaction with randomized treatment and AF for the primary endpoint. Among medically managed high-risk ACS patients receiving DAPT, AF was associated with higher unadjusted risks of ischemic and bleeding outcomes that were similar by treatment group.

Topics: Acute Coronary Syndrome; Aged; Aspirin; Atrial Fibrillation; Chi-Square Distribution; Clopidogrel; Double-Blind Method; Drug Therapy, Combination; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Linear Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Stroke; Ticlopidine; Time Factors; Treatment Outcome

The efficacy and safety of dual antithrombotic therapy (DAT) with oral anticoagulant and P2Y12 inhibitors (P2Y12i) in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) have not been well investigated. The purpose of this study was first to evaluate clinical outcomes of DAT with P2Y12i compared with triple antithrombotic therapy (TAT), and then to compare DAT with low-dose prasugrel and DAT with clopidogrel, in patients with AF undergoing PCI.. This study was a multicenter, non-interventional, prospective and retrospective registry. A total of 710 patients with AF undergoing PCI between January 2015 and March 2021 at 15 institutions were analyzed. Clinical outcomes within 1 year, including major adverse cardiovascular events (MACE) and major bleeding events (BARC 3 or 5) were compared between patients receiving DAT (n = 239) and TAT (n = 471), and then, compared among prasugrel-DAT (n = 82), clopidogrel-DAT (n = 157), and TAT.. The DAT group showed significantly lower incidence of MACE and major bleeding events compared with the TAT group (log-rank p = 0.013 and 0.047). In the multivariable Cox regression analyses, DAT (p = 0.028), acute coronary syndrome (p = 0.025), and anemia (p = 0.015) were independently associated with MACE. In addition, anemia (p = 0.022) was independently associated with, and DAT (p = 0.056) and thrombocytopenia (p = 0.051) tended to be associated with, major bleeding events. When analyzed among the prasugrel-DAT, clopidogrel-DAT, and TAT groups, there were no significant differences in clinical outcomes between the prasugrel-DAT and clopidogrel-DAT groups, and similar trends were observed for both 2 groups in comparison with the TAT group.. In AF patients undergoing PCI, DAT was associated with lower incidence of MACE and major bleeding events compared with TAT. In comparison of P2Y12i, there might be no significant difference in the incidence of MACE and bleeding events between prasugrel-based DAT and clopidogrel-based DAT.

Topics: Anticoagulants; Atrial Fibrillation; Clopidogrel; Fibrinolytic Agents; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Retrospective Studies

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Humans; Japan; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Registries

Though prasugrel is one of the important P2Y. Freshly isolated rat ventricular myocytes were used in this study. Myocyte contraction was measured during electrical stimulation of cardiomyocytes and the action potential (AP) recordings were obtained with current clamp mode of the patch-clamp amplifier.. AP duration and fractional shortening of ventricular myocytes did not show any change with the administration of 1μM of prasugrel. However, remarkable depolarization of resting membrane potential followed by apparent fibrillation episodes was detected in the cardiomyocytes. Similar events were observed in the contractile activity of myocytes during field stimulation. Also, a higher concentration of prasugrel (10μM) elicited repeated fibrillations, which disappeared after washout or nitric oxide synthase (NOS) inhibition with L-NAME. In contrast, the same concentration of ticagrelor, another P2Y. Prasugrel, a widely used antithrombotic agent, may induce depolarization in the membrane potential of myocytes as well as fibrillation via NO mediated pathway.

Topics: Action Potentials; Animals; Atrial Fibrillation; Dose-Response Relationship, Drug; Electric Stimulation; Heart Ventricles; Myocardial Contraction; Myocytes, Cardiac; Nitric Oxide; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Rats, Wistar; Time Factors; Ventricular Function

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

Atrial fibrillation guidelines recommend long-term use of warfarin according to a patient's predicted risk of stroke. After acute myocardial infarction, however, combining warfarin and antiplatelet medications poses challenges.. By using data from more than 69,255 patients with acute myocardial infarction who were enrolled in the National Cardiovascular Data Registry's Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines at 309 hospitals from July 1, 2008, to September 30, 2009, we describe the characteristics and outcomes of the population with myocardial infarction with atrial fibrillation diagnosed within 2 weeks before index myocardial infarction admission (7.1%, N=4947). Use of discharge antithrombotic therapy is described overall and across levels of predicted stroke and bleeding risks.. Compared with patients without atrial fibrillation, those with atrial fibrillation before their index myocardial infarction were older and had more comorbidities and worse in-hospital outcomes. Only 32.5% of patients with atrial fibrillation were taking warfarin before their myocardial infarction admission. In these patients, use of warfarin at discharge increased with higher Congestive heart failure, Hypertension, Age, Diabetes, Stroke [Doubled] (CHADS(2)) risk strata (28.5%, 34.6%, and 43.5% for CHADS(2) scores 0, 1, and ≥2; P<.001) and increased in patients at low, intermediate, and high risk of bleeding (25.4%, 42.3%, and 42.1%; P=.004). Triple therapy at discharge (aspirin plus clopidogrel plus warfarin) was used in a minority of this population (14.6%).. Use of warfarin at discharge in patients with atrial fibrillation is greater among those with higher stroke and bleeding risks, but despite higher-risk profiles, less than half received warfarin at discharge. These findings highlight that clarification is needed to guide choice of antithrombotic therapy for patients with both atrial fibrillation and acute myocardial infarction.

Topics: Adrenergic beta-Antagonists; Age Factors; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Comorbidity; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Myocardial Infarction; Patient Discharge; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Research Design; Risk Assessment; Stroke; Thiophenes; Ticlopidine; Treatment Outcome; Warfarin