Update in dual antiplatelet therapy in patients with ischemic artery disease (original) (raw)
Related papers
Combined Antiplatelet Therapy: Still a Sweeping Combination in Cardiology
Cardiovascular & Hematological Agents in Medicinal Chemistry, 2013
Platelets play a key role in the pathogenesis of atherothrombosis, involved in both the development and progression of atherosclerotic heart disease, and the attendant acute thrombotic complications. Antiplatelet therapy constitutes a mainstay therapy for patients with acute coronary syndromes and generally high-risk patients with atherothrombosis. Until recently, dual antiplatelet therapy (DAPT) for the treatment and prevention of the complications of atherothrombotic disease was traditionally limited to aspirin plus clopidogrel. However, a most important pertaining issue emerged, that of the occurrence of drug-resistance or tolerance observed in some patients for both these antithrombotic agents, which limited the efficacy and applicability of this combined therapy.The availability of the newer thienopyridine, prasugrel, and the cyclopentyl-triazolopyrimidine, ticagrelor, represents an important addition to the physician's armamentarium. Dual antiplatelet therapy with aspirin and clopidogrel or one of the newer agents interferes with platelet activation in complementary, but separate pathways. Aspirin irreversibly inhibits cyclooxygenase, thus preventing the production of thromboxane A 2 , which is a prothrombotic and vasoconstrictive substance. Thienopyridines (clopidogrel/prasugrel) irreversibly and ticagrelor reversibly prevent and inhibit platelet activation by blocking one of the three known adenosine 5'-diphosphate (ADP) receptors (the P2Y 12 receptor) on the platelet surface, thus interfering with platelet activation, degranulation and aggregation. Each of these antiplatelet agents has a protective effect against adverse vascular events; classical DAPT with aspirin and clopidogrel has an even stronger antiplatelet effect compared with either agent alone, however DAPT combining aspirin with one of the newer more potent agents translates into superior antithrombotic protection in atherothrobotic vascular disease, albeit at an increased, though not inordinately, risk for bleeding complications.
European heart journal supplements : journal of the European Society of Cardiology, 2018
Dual antiplatelet therapy (DAPT) with aspirin and a P2Y receptor inhibitor is the cornerstone of pharmacologic management of patients with acute coronary syndrome (ACS) and/or those receiving coronary stents. Long-term (>1 year) DAPT may further reduce the risk of stent thrombosis after a percutaneous coronary intervention (PCI) and may decrease the occurrence of non-stent-related ischaemic events in patients with ACS. Nevertheless, compared with aspirin alone, extended use of aspirin plus a P2Y receptor inhibitor may increase the risk of bleeding events that have been strongly linked to adverse outcomes including recurrent ischaemia, repeat hospitalisation and death. In the past years, multiple randomised trials have been published comparing the duration of DAPT after PCI and in ACS patients, investigating either a shorter or prolonged DAPT regimen. Although the current European Society of Cardiology guidelines provide a backup to individualised treatment, it appears to be diffi...
Journal of Cardiovascular Development and Disease
Dual antiplatelet therapy (DAPT), consisting of the combination of aspirin and an inhibitor of the platelet P2Y12 receptor for ADP, remains among the most investigated treatments in cardiovascular medicine. While a substantial amount of research initially stemmed from the observations of late and very late stent thrombosis events in the first-generation drug-eluting stent (DES) era, DAPT has been recently transitioning from a purely stent-related to a more systemic secondary prevention strategy. Oral and parenteral platelet P2Y12 inhibitors are currently available for clinical use. The latter have been shown to be extremely suitable in drug-naïve patients with acute coronary syndrome (ACS), mainly because oral P2Y12 inhibitors are associated with delayed efficacy in patients with STEMI and because pre-treatment with P2Y12 inhibitors is discouraged in NSTE-ACS, and in patients with recent DES implantation and in need of urgent cardiac and non-cardiac surgery. More definitive evidence...
Thrombosis Research, 2009
Introduction: Large individual variability in clopidogrel responses has been reported. However, mechanisms of the non-responsiveness are unclear. Our aim was to study the extent of platelet inhibition at the receptor level by in vitro receptor antagonists of P2Y 12 (AR-C69931MX, cangrelor) and P2Y 1 (adenosine 3',5'diphosphate) in aspirin treated patients with coronary artery disease (CAD) prior to and after in vivo clopidogrel. Materials and Methods: 51 aspirin-treated (100 mg/day) patients participated. Blood was collected before and after administration of clopidogrel at 300 mg loading dose on day one, followed by 75 mg/d for four days. Aggregation in platelet-rich plasma was assessed. Results: In 20% of patients clopidogrel failed to inhibit platelet responses to ADP. These non-responders had also decreased sensitivity to an in vitro P2Y 12 -receptor antagonist compared with the responders (mean inhibition of aggregation 25 vs. 32%, difference of means 7% (95% CI 2-12%), P b 0.02). Moreover, the P2Y 12receptor inhibition by in vivo clopidogrel correlated with the inhibition by in vitro ARMX measured prior to administration of clopidogrel. Neither P2Y 1 -receptor activity, thrombin generation while on aspirin nor basal platelet activity associated with clopidogrel responses. Conclusions: Concomitant aspirin and clopidogrel treatment failed to suppress platelet activity in 20% of patients. Non-responders to clopidogrel had decreased responses also to another ADP receptor antagonist, which suggests that the impaired response occurs at the level of P2Y 12 -receptor.
Circulation, 2005
Background— Despite the current standard antiplatelet regimen of aspirin and clopidogrel (with or without glycoprotein IIb/IIIa inhibitors) in percutaneous coronary intervention patients, periprocedural and postprocedural ischemic events continue to occur. Prasugrel (CS-747, LY640315), a novel potent thienopyridine P2Y 12 receptor antagonist, has the potential to achieve higher levels of inhibition of ADP-induced platelet aggregation than currently approved doses of clopidogrel. Methods and Results— Joint Utilization of Medications to Block Platelets Optimally–Thrombolysis In Myocardial Infarction 26 (JUMBO-TIMI 26) was a phase 2, randomized, dose-ranging, double-blind safety trial of prasugrel versus clopidogrel in 904 patients undergoing elective or urgent percutaneous coronary intervention. Patients were randomized to either standard dosing with clopidogrel or 1 of 3 prasugrel regimens. Subjects were monitored for 30 days for bleeding and clinical events. The primary end point of...
Therapeutics and Clinical Risk Management, 2014
Coronary and cerebrovascular atherothrombosis are the leading cause of mortality and morbidity worldwide. Novel antiplatelet agents have been established for the management of patients with clinically evident coronary atherothrombosis and are increasingly used in these patients. These agents, however, have shown limited efficacy in the prevention of cerebrovascular events and potential harm in patients with history of stroke or transient ischemic attack. Herein, the efficacy and safety of two established antiplatelet agents in patients with stroke -aspirin and clopidogrel -are reviewed with a focus on the use and challenges related to novel antiplatelet agents -prasugrel, ticagrelor, and vorapaxar -in patients at risk for and with a history of stroke or transient ischemic attack.
JACC. Cardiovascular interventions, 2015
This study sought to determine whether there is an ideal level of platelet reactivity (PR) to optimize safety and efficacy within the large multicenter ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents) study of 8,582 patients receiving successful drug-eluting stent implantation. Patients with high PR on clopidogrel have a greater incidence of adverse ischemic events after stent implantation, whereas low PR may increase bleeding. Due to limited sample size, previous studies have not been able to adjust for differences in baseline characteristics that may confound the relationship of PR and outcomes. In the ADAPT-DES study, routine platelet function testing (VerifyNow) was performed following clopidogrel loading. To characterize the independent association between PR and clinical events, patients were stratified into quintiles of P2Y12 reaction units (PRU). The PRU medians of the 5 quintiles were 57, 130, 187, 244, and 317 (most to least inhibited). There wa...
Update of Antiplatelet Therapy in Patients Without Known Cardiovascular Disease
Serbian Journal of Experimental and Clinical Research, 2017
Platelet activation and aggregation play a critical role in thrombosis, a fundamental pathophysiologic event responsible for the acute clinical manifestations of atherothrombotic events such as acute coronary syndrome, myocardial infarction, ischemic stroke/transient ischemic attack and peripheral artery disease. Dual antiplatelet therapy (low-dose aspirin plus ADP-P2Y12 receptor blockers) has become the cornerstone of therapy for the management of acute and chronic coronary artery disease and the prevention of ischemic complications associated with percutaneous coronary intervention. However, dual antiplatelet therapy in primary prevention of cardiovascular disease in patients without known cardiovascular disease did not significantly reduce the risk of cardiovascular events, such as myocardial infarction, stroke or death, but significantly increased the rate of bleeding. Furthermore, despite multiple randomized controlled trials evaluating the efficacy and safety of aspirin use in...
Antiplatelet Therapy Prasugrel: A Novel Platelet ADP P2Y12 Receptor Antagonist
Clinical and Applied Thrombosis/Hemostasis, 2010
Novel adenosine diphosphate (ADP) P2Y12antagonists, including prasugrel, ticagrelor, cangrelor and elinogrel, are in various phases of clinical development. These ADP P2Y12antagonists have advantages over clopidogrel ranging from faster onset to greater and less variable inhibition of platelet function. Novel ADP P2Y12antagonists are under investigation to determine whether their use can result in improved antiplatelet activity, faster onset of action, and/or greater antithrombotic effects than clopidogrel, without an unacceptable increase in hemorrhagic or other side effects. Prasugrel (CS-747; LY-640315), a novel third-generation oral thienopyridine, is a specific, irreversible antagonist of the platelet ADP P2Y12receptor. Preclinical and early phase clinical studies have shown prasugrel to be characterized by more potent antiplatelet effects, lower interindividual variability in platelet response, and faster onset of activity compared to clopidogrel. Recent findings from large-sc...