Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platelet-leukocyte interactions are recognised to have pro-inflammatory effects, which may be important in the pathophysiology of ischaemic heart disease. Clopidogrel and the novel intravenous antithrombotic agent AR-C69931MX act at the level of the platelet P2Y12 receptor, which is known to amplify platelet activation, aggregation and other responses induced by numerous platelet agonists. We studied the effects of clopidogrel and aspirin on ADP-induced platelet-leukocyte conjugate formation and P-selectin expression in healthy volunteers. The effects of clopidogrel and AR-C69931MX administered to patients with ischaemic heart disease were also assessed. AR-C69931MX and aspirin were also studied in vitro. Clopidogrel and AR-C69931MX suppressed ADP-induced platelet aggregation, P-selectin expression and platelet-leukocyte conjugate formation whereas aspirin had no inhibitory effect. These effects of clopidogrel and AR-C69931MX may confer therapeutic benefits in the management of acute coronary syndromes.
 ...
PMID:Inhibition of ADP-induced P-selectin expression and platelet-leukocyte conjugate formation by clopidogrel and the P2Y12 receptor antagonist AR-C69931MX but not aspirin. 1235 80

Prasugrel, trade name Effient, is an investigational new antiplatelet drug currently under review for clinical use by the Food and Drug Administration. It is a thienopyridine analog with a structure similar to that of clopidogrel and ticlopidine. Thienopyridine derivatives inhibit platelet aggregation induced by adenosine diphosphate by irreversibly inhibiting the binding of adenosine diphosphate to the purinergic P2Y12 receptor on the platelet surface. Prasugrel has been shown to be a potent antiplatelet agent with a faster, more consistent, and greater inhibition of platelet aggregation compared with clopidogrel. It is debatable, however, how effectively these pharmacologic benefits will translate to clinical benefits. The results of the large TRITON-TIMI 38 trial, which compared prasugrel and clopidogrel in patients with acute coronary syndrome who were scheduled to receive coronary stents, demonstrated a significant reduction in ischemic events, including stent thrombosis, with prasugrel, but with an increased risk of major bleeding. The exact role of prasugrel in the management of ischemic heart disease is still being defined, but the risk:benefit ratio will likely play a major role in directing the best place for therapy with this new agent.
 ...
PMID:Prasugrel: a new antiplatelet drug for the prevention and treatment of cardiovascular disease. 1892 35

In a series of articles the authors consider clinical pharmacology and experience of clinical application of blockers of platelet P2Y12 receptors, most well known representatives of which ticlopidine and clopidogrel according to chemical structure belong to thienopyridine derivatives. In the second communication we describe in detail clinical pharmacokinetics and pharmacodynamics of the most often used thienopyridine derivative - clopidogrel. We discuss results of randomized studies and clinical observations which have shown that pharmacokinetics of clopidogrel might vary substantially in dependence of polymorphisms of genes responsible for synthesis of P2Y12 receptors of platelets or cytochromic isoenzymes P-450 CYP of liver with participation of which formation of active metabolite of clopidogrel occurs. Contrary to practically healthy people in patients with various forms of ischemic heart disease (IHD) concomitant therapy, for instance some statins and calcium antagonists, can affect clopidogrel pharmacokinetics. Pharmacodynamics of clopidogrel in patients with IHD with acute coronary syndrome or diabetes mellitus or before percutaneous coronary interventions (PCI) also differs from that in healthy people, because in these patients hyperaggregation of platelets takes place initially and antiaggregatory action of clopidogrel is less expressed. In 10-30% of patients with IHD partial or complete resistance to antiaggregation action of clopidogrel is detected, which according to some observations is combined with elevated risk of thrombotic cardiac complications after PCI. Possible causes of resistance to clopidogrel and ways of its overcoming are discussed.
 ...
PMID:[Thienopyridines in the treatment and prevention of cardiovascular diseases. Part II. Clinical pharmacology of clopidogrel]. 1984 26

Current clinical guidelines recommend dual antiplatelet agents namely aspirin and clopidogrel for the treatment of patients suffering from acute coronary syndrome (ACS). But the efficacy of clopidogrel is variable as it is a pro-drug, which has to be metabolized to become an active drug thus exhibiting variable platelet inhibition, increases risk of bleeding, stent thrombosis, and ischemia. To overcome this limitation, prasugrel was developed with increased antiplatelet activity thereby reducing the risk of myocardial ischemia and stent thrombosis. This action of prasugrel was associated with an increased risk of major bleeding. Finally, a novel reversible and direct-acting oral adenosine diphosphate (ADP) receptor antagonist, ticagrelor was developed that showed consistent and increased P2Y12 inhibition with similar incidence of bleeding but greater reduction in cardiac events compared to clopidogrel. The focus of this article is to review ticagrelor as a new class of P2Y12 inhibitor.
 ...
PMID:Novel antiplatelet agent ticagrelor in the management of acute coronary syndrome. 2119 49

Antiplatelet treatment is an important element in the medical treatment of patients with stable angina. Single antiplatelet therapy with low-dose aspirin is recommended in the absence of contraindications in all patients with diagnosed chronic stable angina and ischemic heart disease. Dual antiplatelet therapy is recommended initially for all patients with stable angina undergoing elective angioplasty with the duration of P2Y12 antagonist administration depending on the type of coronary stent. Despite the demonstrated clinical benefit in a wide range of patients, residual risk of ischemic events with aspirin and a P2Y12 inhibitor has also been attributed to the fact that these agents do not inhibit all pathways involved in platelet activation and aggregation. Other platelet activation pathways, including the PAR-1 pathway activated by thrombin (the most potent platelet activator), remain active in the presence of current antiplatelet agents. A combination of current therapies with novel agents could provide more comprehensive platelet inhibition leading to incremental decrease of cardiovascular events at the expense of increased bleeding risk. The current review presents traditional and novel antiplatelet treatment options and discusses the indications for aggressive antiplatelet management in patients with stable angina pectoris.
 ...
PMID:Novel anti-platelet agents for the treatment of stable angina pectoris. 2301 12

The review is devoted to pharmacogenetics of clopidogrel and its value for the clinic. Mechanism of action of clopidogrel and main trials which has proven its efficacy are presented as well as results of main large studies including authors own results demonstrating dependence of clinical efficacy of clopidogrel on carriage of polymorphisms of gene of CYP2C19 which accomplishes metabolism of the drug in the liver. Problems of interaction of clopidogrel with proton pump inhibitors and other drugs as well as ways of overcoming "resistance" to clopidogrel are considered. Clinical efficacy of other P2Y12 receptors of platelets in patients with IHD is characterized in comparison with clopidogrel.
 ...
PMID:[Pharmacogenetics of clopidogrel and its clinical significance]. 2309 46

Although clopidogrel is more effective in preventing thrombotic complications than aspirin alone in a broad spectrum of patients with ischemic heart disease, many of its limitations were recently brought to light including a delayed onset of action and highly unpredictable P2Y12-receptor inhibition. New-generation ADP-receptor antagonists, such as prasugrel and ticagrelor, were designed and developed to overcome these limitations, providing a more rapid, more reliable and more potent P2Y12-receptor inhibition. These pharmacodynamic benefits of new-generation antiplatelet agents were translated into significant clinical advantage among patients with acute coronary syndrome (ACS), especially in preventing stent thrombosis. However, the downsides of the unselected use of novel P2Y12-receptor antagonists include higher risk of bleeding and increased costs. Platelet reactivity testing might become a useful tool to help balance between bleeding and thrombosis with P2Y12-receptor antagonists; however, its role in clinical practice for patients undergoing percutaneous coronary intervention (PCI) remains uncertain. The aim of this viewpoint article is to summarize the currently available evidence supporting a role of platelet function testing in patients with ACS after PCI.
...
PMID:Current evidence for monitoring platelet reactivity in acute coronary syndrome: a plea for individualized antiplatelet treatment. 2329 Sep 51

Ischemic heart disease and cerebrovascular disease remain major health problems with associated mortality and quality-of-life consequences. Antiplatelet agents, including thienopyridines and the new P2Y12 inhibitors, have been shown to improve survival in the secondary prevention setting. We review the available evidence on the effectiveness and safety of previous established as well as novel antithrombotic agents in the secondary prevention of cardiovascular disease with a special focus on cerebrovascular disease.
 ...
PMID:Antiplatelet treatment in the secondary prevention of coronary and cerebrovascular disease: is there any place for novel agents? 2396 69

Mortality and morbidity in acute coronary syndromes (ACSs), caused principally by plaque erosion or rupture leading to thrombus formation and myocardial ischemia, have been reduced by a combination of antithrombotic agents (antiplatelet drugs and anticoagulants) and early revascularization. Aspirin is the foundation antiplatelet agent. New P2Y12 receptor inhibitors (prasugrel and ticagrelor) have clear benefits compared with clopidogrel for dual antiplatelet therapy, and cangrelor or vorapaxar, a thrombin receptor inhibitor, may be of value in specific settings. Anticoagulation uses 1 of 4 choices: bivalirudin, unfractionated heparin, enoxaparin, and fondaparinux. Moreover, some patients (such as those who have chronic atrial fibrillation) require triple therapy with aspirin, clopidogrel, plus an anticoagulant, frequently a vitamin K antagonist. New oral anticoagulants have been shown to be at least as effective as vitamin K antagonists in atrial fibrillation and led to fewer bleeding complications. Finally, the combination of aspirin, clopidogrel, and low-dose rivaroxaban has recently been approved by the European Medicines Agency (but not the Food and Drug Administration) for secondary prevention after ACS. Several strategies have been developed to balance the potential benefit of antithrombotic therapy against the risk of bleeding complications, for example, radial access in coronary angiography or restricted use of combination therapy, and others are under investigation, such as discontinuation of aspirin. This overview summarizes the current status of antithrombotic therapy in ACS and describes strategies currently explored to optimize its benefit/risk ratio.
...
PMID:Antiplatelet and anticoagulation agents in acute coronary syndromes: what is the current status and what does the future hold? 2544 Jul 88

Dual antiplatelet therapy (DAPT), which is the combination of aspirin and a platelet P2Y12 inhibitor, is the cornerstone of secondary prevention in ischemic heart disease requiring intracoronary stenting. Although the efficacy of DAPT in the reduction of ischemic events has been well validated, the optimal duration, and indeed combination, of therapy is yet to be established. This area continues to attract debate with new developments in stent design and antiplatelet agents, as well as evolving clinical skill levels. Presently, clinical guidelines advocate the use of DAPT for 6-12 months following drug-eluting stent (DES) implantation, but this can vary according to clinical indication, bleeding risk, and country of practice. Concerns have arisen that unnecessary prolongation of DAPT may be associated with increased bleeding events, as well as cost. Whether these guidelines effectively cater to current stenting techniques, devices, and antiplatelet agents remains to be determined. This review analyzes contemporary issues surrounding DAPT following DES implantation, as researchers continue to seek to strike the optimal balance between bleeding and thrombotic risk. Although reduced DAPT durations continue to show promising results in preventing ischemic events while also mitigating bleeding risk, ultimately the consideration of clinical presentation as well as medical and social history is paramount to guiding the optimal duration and cessation of DAPT.
...
PMID:Antiplatelet therapy after drug-eluting stent implantation. 2546 22


1 2 Next >>