fondaparinux and Coronary-Thrombosis

Anticoagulation is an integral part of both fibrinolytic therapy and percutaneous intervention (PCI) in the reperfusion treatment of ST-segment elevation AMI (STEMI).. This article reviews the choices of adjunctive anticoagulation regimens. Readers will appreciate the complexities of anticoagulation and the variable risk of clotting with ischemic/thrombotic complications versus that of bleeding. Antiplatelet therapy with aspirin and clopidogrel is recommended with fibrinolysis and PCI. Newer P2Y(12) inhibitors such as prasugrel and ticagrelor have been shown to reduce cardiovascular death, myocardial infarction (MI), stroke and stent thrombosis, as compared with clopidogrel. Ticagrelor has also been shown to reduce mortality. Glycoprotein IIb/IIIa inhibitors, by blocking the final pathway of platelet clumping with each other through bridging with fibrinogen, have the ability to disaggregate platelets, hence the potential for reducing thrombotic complications as well as increasing bleeding in patients undergoing PCI bleeding risks. Enoxaparin reduces death and MI compared with unfractionated heparin (UFH) with fibrinolytic therapy. There was a trend for a reduction in death, MI procedural failure or non-coronary artery bypass grafting (CABG) major bleeding compared with UFH in primary PCI. In primary PCI, bivalirudin has the advantage over UFH of inhibiting clot bound thrombin and reduces bleeding and mortality compared with the use of UFH plus glycoprotein IIb/IIIa inhibitors. Combinations of P2Y(12) antagonists and bivalirudin need to be tested to optimize the balance between efficacy and bleeding.. This field is rapidly evolving with multiple appropriate approaches.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Thrombosis; Electrocardiography; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Polysaccharides; Thrombolytic Therapy

The activation of coagulation mechanisms plays a central role in the pathogenesis of acute coronary syndromes (ACS). Administration of unfractionated heparin (UFH) and low molecular weight heparins (LMWH), agents preventing the progression of thrombus formation, is a crucial therapeutic strategy. However, some limitations related to their use have recently stimulated the development of new synthetic agents.. To evaluate the clinical efficacy and safety of factor Xa inhibitors for treatment of ACS compared to UFH or LMWH.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) of the Cochrane Library (Issue 1, 2008), PubMed, EMBASE and LILACS as well as the publications from International Congresses and the reference lists of the selected studies in December 2008.. We used randomized controlled trials (RCTs) comparing factor Xa inhibitors to UFH or LMWH during the course of ACS. Outcome measures included all-cause mortality, myocardial infarction, re-infarction, ischemia recurrence, and adverse events.. The selection, quality assessment and data extraction of the included trials were done independently by two authors and disagreements were resolved by consensus. Data were analysed by the use of risk ratio (RR) with 95% confidence interval (CI), and the numbers needed to treat (NNT) were reported as needed.. A total of four RCTs involving 27,976 subjects were included. Fondaparinux was the only factor Xa inhibitor identified in our included RCTs. Fondaparinux appeared to be related to a lower risk in all-cause mortality at 90 to 180 days (RR 0.89; 95% CI 0.81 to 0.97), especially in the group where enoxaparin (a LMWH) was the control drug. Fondaparinux was also associated with a lower risk in major and minor bleeding at 30 days compared to enoxaparin (RR 0.63, 95% CI 0.55 to 0.73; RR 0.34, 95% CI 0.28 to 0.43, respectively), but not when compared to UFHs (RR 1.41; 95% CI 0.49 to 4.10; RR 0.70, 95% CI 0.14 to 3.39 respectively).. The therapeutic efficacy of factor Xa inhibitors in ACS seemed to be related to a reduced risk in all-cause mortality at 90 to 180 days, with a better safety profile than enoxaparin in terms of reduce incidence of major and minor bleeding.

Topics: Acute Coronary Syndrome; Anticoagulants; Coronary Thrombosis; Factor Xa Inhibitors; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Randomized Controlled Trials as Topic

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Clinical Trials as Topic; Coronary Thrombosis; Endothelium, Vascular; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Hirudins; Humans; Myocardial Ischemia; Peptide Fragments; Platelet Activation; Polysaccharides; Postoperative Complications; Recombinant Proteins; Thrombin

Two new classes of anticoagulants are actually developed which would change in the near future our strategies for the prevention and the treatment of venous thromboembolic events. These two classes are the anti-factor Xa and anti-factor IIa (direct antithrombin) agents. Among the anti factor Xa, the pentasaccharides are initiating their clinical use. Fondaparinux is a synthetic form of the natural pentasaccharide, its pharmacokinetics allows one s.c. administration/24 hours. It is active in prevention and treatment of venous thromboembolic and coronary thrombotic events. A modified form (idraparinux) whose pharmacokinetics allows one administration only once a week should have the same type of efficacy. Among direct antithrombin agents, hirudin and derivatives have been developed in the past decade with a limited use due to several drawback. More recently synthetic direct antithrombins modified to allow oral route have been developed, the most advanced in development, melagatran, is active in the prevention and treatment of venous thromboembolic and coronary thrombotic events. It could allow (if confirmed by clinical trials) a complete oral treatment of deep vein thrombosis without any biological monitoring. Melagatran is also active in the prevention of arterial thromboembolic events on atrial fibrillation. But other molecular forms of synthetic orally active direct antithrombin are also in development. Besides these important changes in our therapeutics which should appear in a near future, molecules aimed at other target are also tested: the most advanced are those antagonizing the initial phase of tissue factor activation of factor VII but other strategies are being tested such as stimulation of fibrinolysis. These new drugs at our disposal to treat venous thromboembolism should modify completely our handling of the patients. But additionally the numerous clinical trials necessary to prove the efficacy of the drugs, modify our understanding in the implication of the coagulation and in the physiopathogeny of thrombotic events.

Topics: Administration, Oral; Azetidines; Benzylamines; Clinical Trials as Topic; Coronary Thrombosis; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Glycine; Hirudin Therapy; Humans; Orthopedics; Polysaccharides; Prodrugs; Prothrombin; Research; Thrombin; Thromboembolism; Time Factors; Venous Thrombosis

Acute coronary syndromes encompass a spectrum of conditions, including myocardial infarction and unstable angina. These syndromes are related to the formation and disruption of atherosclerotic plaque. Rupture of plaque leads to thrombin generation, fibrin deposition, and platelet aggregation, ultimately resulting in restriction of blood flow and ischemia of cardiac tissue. Percutaneous coronary intervention (PCI), including angioplasty and coronary stent placement, has been developed to open occluded arteries. The frequency with which these procedures are performed speaks to their largely successful outcomes. However, the mechanical manipulations of PCI result in additional plaque rupture and damage to the vessel wall, exposing subendothelial components to blood and resulting in the initiation of the clotting cascade and in platelet activation. Left unchecked, these intertwined processes lead to formation of arterial thrombi at the site of endothelial damage, and potentially to abrupt vessel closure or embolization of thrombi into the distal microcirculation. Thrombin plays a central role in thrombus formation and platelet activation, and its inhibition significantly reduces thrombus-related sequelae. Current antithrombotic strategies during PCI are based on the traditional indirect thrombin inhibitor heparin. Heparin has several limitations in efficacy and safety, due in part to its indirect mechanism of action. Bivalirudin, a direct thrombin inhibitor, offers significant improvement over heparin in the clinical outcomes and risks associated with PCI.

Topics: Angioplasty, Balloon, Coronary; Arginine; Clinical Trials as Topic; Coronary Disease; Coronary Thrombosis; Fibrinolytic Agents; Fondaparinux; Heparin; Hirudins; Humans; Peptide Fragments; Pipecolic Acids; Polysaccharides; Recombinant Proteins; Sulfonamides; Thrombin

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Thrombosis; Diabetes Complications; Drug-Eluting Stents; Female; Fondaparinux; Humans; Obesity; Polysaccharides

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Thrombosis; Enoxaparin; Evidence-Based Medicine; Fondaparinux; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Polysaccharides; Recombinant Proteins; Risk Assessment; Risk Factors; Treatment Outcome

Topics: Administration, Cutaneous; Angina, Unstable; Anticoagulants; Cardiac Catheterization; Comorbidity; Coronary Thrombosis; Enoxaparin; Factor X; Fondaparinux; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Polysaccharides; Syndrome; Troponin