fondaparinux and Myocardial-Infarction

The most recent joint guidelines from the American Heart Association (AHA) and American College of Cardiology (ACC) on the management of non-ST-elevation acute coronary syndromes (NSTE-ACS) are a result of a substantial and considered undertaking, and those involved deserve much recognition for their efforts. However, the handling of anticoagulants seems somewhat inadequate, and this is a highly-relevant matter when managing NSTE-ACS.. Among areas of potential uncertainty, emergency medicine professionals might still be left wondering about the particulars of anticoagulant therapy when pursuing ischemia-guided management of NSTE-ACS (that is, managing NSTE-ACS without an intent for early invasive measures, such as coronary angiography and revascularization). This review seeks to provide insight into this question.. Relevant clinical trials are appraised and translated into clinical context for emergency medicine professionals, including the implications of noteworthy advancements in the management of NSTE-ACS.. Although current guidelines from the AHA and ACC suggest enoxaparin has better evidence than other anticoagulants in the setting of NSTE-ACS management, careful review of the evidence shows this is not actually clearly supported by the available evidence in the era of contemporary management. Unless and until better contemporary data emerge, emergency medicine professionals must carefully weigh the available evidence, its limitations, and the possible clinical implications of the various anticoagulant options when managing NSTE-ACS.

Topics: Acute Coronary Syndrome; American Heart Association; Angina, Unstable; Anticoagulants; Clinical Trials as Topic; Disease Management; Emergency Service, Hospital; Emergency Treatment; Enoxaparin; Fondaparinux; Heparin; Humans; Myocardial Infarction; Polysaccharides; Practice Guidelines as Topic; Societies, Medical; Treatment Outcome; United States

A number of studies have evaluated the efficacy and safety of fondaparinux versus low-molecular-weight heparin (LMWH) in patients with acute coronary syndrome (ACS), but the findings were not consistent across these studies.. Electronic databases and article references were searched for studies that assessed fondaparinux versus LMWH in ACS patients.. Six studies met the inclusion criteria. There was a lower risk of major adverse cardiac events (MACE) with fondaparinux-based regimens both in randomized controlled trials (RCT; risk ratio, RR: 0.91, p = 0.04) and observational studies (RR: 0.85, p < 0.0001). Mortality decreased in fondaparinux-treated patients in RCT (RR: 0.84, p = 0.02), but not in observational studies (RR: 1.44, p = 0.64). For the analysis of myocardial infarction (MI), recurrent ischemia and stroke, none of the studies showed significant results. In addition, fondaparinux lowered the risk of major bleeding in RCT (RR: 0.62, p < 0.0001) and observational studies (RR: 0.65, p < 0.0001). The net clinical outcome also favored fondaparinux over LMWH in RCT (RR: 0.82, p < 0.0001) and observational studies (RR: 0.84, p < 0.0001).. Among ACS patients, a fondaparinux-based regimen presented advantages regarding MACE and major bleeding, and a net clinical benefit compared with LMWH, although the benefit is minimal regarding MACE. For death, MI, recurrent ischemia and stroke, fondaparinux has not shown significant benefits.

Topics: Acute Coronary Syndrome; Anticoagulants; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Myocardial Infarction; Polysaccharides; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome

To investigate the relative benefits of unfractionated heparin, low molecular weight heparin(LMWH), fondaparinux, and bivalirudin as treatment options for patients with ST segment elevation myocardial infarction undergoing percutaneous coronary intervention (PCI).. Mixed treatment comparison and direct comparison meta-analysis of randomized trials in the era of stents and P2Y12 inhibitors.. A search of Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) for randomized trials comparing unfractionated heparin plus glycoprotein IIb/IIIa inhibitor(GpIIb/IIIa inhibitor), unfractionated heparin, bivalirudin, fondaparinux, or LMWH plus GpIIb/IIIa inhibitor for patients undergoing primary PCI.. The primary efficacy outcome was short term (in hospital or within 30 days) major adverse cardiovascular event; the primary safety outcome was short term major bleeding.. We identified 22 randomized trials that enrolled 22,434 patients. In the mixed treatment comparison models, when compared with unfractionated heparin plus GpIIb/IIIa inhibitor, unfractionated heparin was associated with a higher risk of major adverse cardiovascular events (relative risk 1.49 (95% confidence interval 1.21 to 1.84), as were bivalirudin (relative risk 1.34 (1.01 to 1.78)) and fondaparinux (1.78 (1.01 to 3.14)). LMWH plus GpIIb/IIIa inhibitor showed highest treatment efficacy, followed (in order) by unfractionated heparin plus GpIIb/IIIa inhibitor, bivalirudin, unfractionated heparin, and fondaparinux. Bivalirudin was associated with lower major bleeding risk compared with unfractionated heparin plus GpIIb/IIIa inhibitor (relative risk 0.47 (0.30 to 0.74)) or unfractionated heparin (0.58 (0.37 to 0.90)). Bivalirudin, followed by unfractionated heparin, LMWH plus GpIIb/IIIa inhibitor, unfractionated heparin plus GpIIb/IIIa inhibitor, and fondaparinux were the hierarchy for treatment safety. Results were similar in direct comparison meta-analyses: bivalirudin was associated with a 39%, 44%, and 65% higher risk of myocardial infarction, urgent revascularization, and stent thrombosis respectively when compared with unfractionated heparin with or without GpIIb/IIIa inhibitor. However, bivalirudin was associated with a 48% lower risk of major bleeding compared with unfractionated heparin plus GpIIb/IIIa inhibitor and 32% lower compared with unfractionated heparin alone.. In patients undergoing primary PCI, unfractionated heparin plus GpIIb/IIIa inhibitor and LMWH plus GpIIb/IIIa inhibitor were most efficacious, with the lowest rate of major adverse cardiovascular events, whereas bivalirudin was safest, with the lowest bleeding. These relationships should be considered in selecting anticoagulant therapies in patients undergoing primary PCI.

Topics: Anticoagulants; Antithrombins; Fondaparinux; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Integrin beta3; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Polysaccharides; Purinergic P2Y Receptor Antagonists; Recombinant Proteins; Stents; Thrombosis; Treatment Outcome

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

Superficial vein thrombosis (SVT) occurs at least as frequent as deep vein thrombosis (DVT), and shares common risk factors with venous thromboembolism. The CALISTO trial was the first to provide specific recommendations for the pharmacologic treatment of SVT. Before treatment is initiated, an accompanying DVT must be excluded and the proximal extension of the SVT assessed. If the proximal extension of the thrombus is closer than 3 cm towards the deep vein system, it should be treated like DVT. Under certain conditions treatment with fondaparinux is indicated in acute symptomatic SVT. Furthermore, compression treatment is recommended. Extracranial carotid artery stenosis can be treated by either surgical thrombarterectomy or catheter based endovascular stent implantation. Trials comparing the two methods have not provided conclusive results on whether the two strategies are equally safe and effective. Considering the latest data from RCTs, careful patient selection (symptoms, comorbidities, age, anatomy, re-stenosis) including individual interdisciplinary discussion appears of ample importance. To date no information is available on whether patients with asymptomatic high grade carotid stenosis receiving "best medical therapy" should be considered for revascularisation in general or only in selected circumstances.

Topics: Angioplasty; Anticoagulants; Carotid Artery, External; Carotid Stenosis; Endarterectomy, Carotid; Fondaparinux; Humans; Multicenter Studies as Topic; Myocardial Infarction; Polysaccharides; Prospective Studies; Pulmonary Embolism; Randomized Controlled Trials as Topic; Risk Factors; Stents; Stockings, Compression; Stroke; Survival Rate; Venous Thrombosis

New data have re-established the importance of anticoagulation of patients with ST segment elevation myocardial infarction (STEMI), both as an adjuvant to reperfusion therapy or in patients ineligible for reperfusion. Recent randomized trials have found newer agents to be superior to conventional unfractionated heparin. This article summarizes current understanding of the underlying pathophysiology of STEMI and provides a comprehensive review of emerging trial data for low molecular weight heparins, anti-factor Xa agents and direct thrombin inhibitors in this setting.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Blood Coagulation; Clinical Trials as Topic; Factor Xa Inhibitors; Fondaparinux; Heparin, Low-Molecular-Weight; Hirudin Therapy; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Polysaccharides; Recombinant Proteins; Thrombin; Thrombolytic Therapy; Treatment Outcome

Coronary artery disease is the leading cause of death in the UK with a high clinical, social and economic burden. The management of acute coronary syndromes is rapidly evolving and clinicians are constantly challenged with incorporating new clinical pathways and guidelines into their practices. It is important for clinicians to have a sound working knowledge of acute coronary syndromes, and be updated on the emerging evidence to guide therapy and improve outcomes in these patients.

Topics: Angioplasty, Balloon, Coronary; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Antithrombins; Clopidogrel; Fondaparinux; Heparin, Low-Molecular-Weight; Hirudins; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Polysaccharides; Recombinant Proteins; Thrombolytic Therapy; Ticlopidine

The increasing incidence of patients who develop acute coronary syndrome (ACS) stresses the importance of effective initial treatment to reduce morbidity and mortality. The recommended initial therapeutic regimen for patients with ACS includes both anticoagulants and antiplatelet agents to prevent excessive coronary thrombosis, stroke, and further coronary events. Most commonly, unfractionated heparin (UFH) is used for initial antithrombotic treatment of ACS, despite limited published evidence regarding effectiveness and safety (bleeding complications). Therefore, this treatment regimen is primarily based upon expert opinion rather than evidence-based medicine. Studies addressing the dilemma of effectiveness and increased risk of bleeding when using UFH and low molecular weight heparin (LMWH) in patients with ACS showed superior clinical outcome in patients treated with LMWH. Nevertheless, the concurrent increased risk of bleeding while using anticoagulants is a severe problem and negatively impacts upon clinical outcome. Furthermore, non-hemorrhagic side effects of heparin such as heparin-induced thrombocytopenia (HIT), and skin reactions at the site of subcutaneous injection are reduced but not abolished by replacing UFH with LMWH. The limitations of UFH and LWMH as outlined above provided the impetus for the development of a pentasaccharide, called fondaparinux, which inhibits factor Xa selectively. Fondaparinux has been shown to be as effective as enoxaparin in the prevention of thrombosis in patients undergoing orthopedic surgery and showed similar results compared to enoxaparin or UFH in patients with deep-vein-thrombosis or pulmonary embolism. Recently, a large clinical study addressed the dilemma of the effectiveness and adverse effects of anticoagulation in ACS by comparing fondaparinux and LMWH such as enoxaparin in patients with unstable angina or non ST-segment elevation myocardial infarction (NSTEMI).

Topics: Acute Coronary Syndrome; Angina, Unstable; Anticoagulants; Enoxaparin; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Humans; Myocardial Infarction; Polysaccharides

In addition to antiplatelet therapy with aspirin, anticoagulation therapy with unfractionated heparin decreases the risk of myocardial infarction and death in patients with acute coronary syndromes. However, unfractionated heparin has pharmacologic limitations that limit efficacy and safety. Enoxaparin, fondaparinux, and bivalirudin are new anticoagulant therapy options with either superior efficacy or better safety than unfractionated heparin. Compared with unfractionated heparin, enoxaparin and fondaparinux are easier to administer, do not require monitoring, and facilitate longer treatment duration. Bivalirudin offers advantages for patients undergoing early percutaneous revascularization. Careful attention to dosing and excellent vascular access site management after cardiac catheterization are required to decrease the risk of bleeding and blood transfusion, which have been associated with increased mortality risk.

Topics: Angina, Unstable; Anticoagulants; Electrocardiography; Enoxaparin; Fondaparinux; Heart Conduction System; Heparin, Low-Molecular-Weight; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Polysaccharides; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome

Topics: Angina, Unstable; Anticoagulants; Azetidines; Benzimidazoles; Benzylamines; Brain Ischemia; Clinical Trials as Topic; Coumarins; Dabigatran; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Forecasting; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Morpholines; Myocardial Infarction; Peptide Fragments; Polysaccharides; Prothrombin; Pyrazoles; Pyridines; Pyridones; Recombinant Proteins; Rivaroxaban; Thiophenes; Thrombin; Thrombophilia; Thrombosis; Warfarin

Accomplishing a successful percutaneous coronary intervention in a patient with a suspected or diagnosed heparin-induced thrombocytopenia (HIT) requires the selection of an appropriate alternative anticoagulant and a thorough assessment of bleeding and thrombotic risks. In this review, we suggest an evidence-based management algorithm that takes into account the clinical phase of HIT (acute, recent, and remote HIT) and the associated risk when patients present with acute coronary syndrome. The algorithm also integrates preventive measures directed at decreasing the bleeding risk associated with the antithrombotic and invasive therapies used for HIT and percutaneous coronary intervention.

Topics: Algorithms; Angioplasty, Balloon, Coronary; Anticoagulants; Arginine; Chondroitin Sulfates; Comorbidity; Dermatan Sulfate; Drug Therapy, Combination; Fibrinolytic Agents; Fondaparinux; Heparin; Heparinoids; Heparitin Sulfate; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Pipecolic Acids; Polysaccharides; Recombinant Proteins; Sulfonamides; Syndrome; Thrombocytopenia; Vitamin K

Fondaparinux (Arixtra, GlaxoSmithKline) is a synthetic, selective, activated Factor X inhibitor. On the grounds of its favorable benefit:risk ratio, fondaparinux is approved for the prevention and treatment of venous thromboembolism. Two large trials involving approximately 32,000 patients recently evaluated fondaparinux in the treatment of non-ST elevation acute coronary syndromes and ST elevation acute myocardial infarction. Fondaparinux was compared with enoxaparin or usual care, depending on the setting. A single, once-daily 2.5-mg subcutaneous dose of fondaparinux was used in both studies. After a brief introduction to the drug, this article presents the results obtained in these trials with fondaparinux and compares them with those obtained with other anticoagulants. Overall, it appears that fondaparinux at the single, once-daily dose of 2.5 mg represents a valuable new alternative for the treatment of patients with acute coronary syndromes.

Topics: Acute Coronary Syndrome; Aged; Dose-Response Relationship, Drug; Drug Administration Schedule; Enoxaparin; Female; Fondaparinux; Humans; Injections, Subcutaneous; Male; Middle Aged; Myocardial Infarction; Polysaccharides; Prognosis; Randomized Controlled Trials as Topic; Risk Assessment; Severity of Illness Index; Survival Analysis; Treatment Outcome

The death rate of patients with ST-segment elevation myocardial infarction (STEMI) remains substantial. Fondaparinux is a synthetic selective Factor Xa inhibitor with a high efficacy and good safety, in terms of bleeding risk, in the prevention and treatment of venous thromboembolism, and in the treatment of non-ST elevation acute coronary syndromes (OASIS-5). The OASIS-6 trial was a randomized, double-blind trial comparing fondaparinux 2.5 mg once daily with standard therapy, either placebo or unfractionated heparin according to the indication, in 12092 patients with STEMI. At day 30, fondaparinux significantly reduced the occurrence of the primary efficacy outcome (death or recurrent myocardial infarction) by 14% (p = 0.008). Consistent reductions in both death and recurrent MI were observed at 6-month follow-up. The benefits were significant in patients who received no reperfusion therapy or a thrombolytic agent, but not in patients undergoing primary percutaneous coronary interventions. There was a trend (p = 0.13) towards fewer severe bleeds in the fondaparinux group (1.0% vs 1.3% in the control group). In conclusion, fondaparinux significantly reduced mortality without increasing severe bleeding in patients with STEMI. Overall, the data from the OASIS studies showed that fondaparinux 2.5 mg may represent a new anticoagulant standard in patients with acute coronary syndromes.

Topics: Anticoagulants; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Myocardial Infarction; Polysaccharides; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Research Design; Secondary Prevention; Treatment Outcome

Fondaparinux (Arixtra) is the first selective factor Xa inhibitor approved for use in thromboprophylaxis after orthopaedic surgery. New recently completed trials have also demonstrated the potential of fondaparinux in the prevention of venous thromboembolism (VTE) in other surgical and medical settings and in the treatment of established VTE. In the randomized double-blind PEGASUS study in high-risk abdominal surgery patients, fondaparinux reduced the incidence of VTE from 6.1% with dalteparin to 4.6% (odds ratio reduction = 25.8%, P = 0.14), without increasing the bleeding risk. In the randomized double-blind ARTEMIS trial in acutely ill medical patients, fondaparinux reduced the incidence of VTE from 10.5% with placebo to 5.6% (odds ratio reduction = 49.5%, P = 0.029), without increasing the bleeding risk; there was no pulmonary embolism in the fondaparinux group compared with five, all fatal, in the placebo group (P = 0.029). In the two MATISSE trials, both the efficacy and safety of once daily fondaparinux were at least as good as enoxaparin in the treatment of deep-vein thrombosis (MATISSE-DVT) and unfractionated heparin in the treatment of pulmonary embolism (MATISSE-PE). In patients with coronary artery disease, promising results were obtained in phase II trials and large phase III trials are ongoing. In conclusion, fondaparinux may further improve and simplify the prevention and treatment of thrombosis in a large range of medical and surgical settings.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombin III; Fondaparinux; Humans; Myocardial Infarction; Polysaccharides; Postoperative Complications; Thromboembolism; Venous Thrombosis

Due to their favorable pharmacologic properties and beneficial clinical effects, low molecular weight heparins (LMWHs) have become the standard of care in the prevention and treatment of venous thromboembolism and have also been extensively studied in the treatment of acute coronary syndromes. Pentasaccharide is the first of a new class of synthetic antithrombotics and has been shown to be superior to LMWH in preventing deep vein thrombosis. Hirudin is the most potent direct thrombin inhibitor and has provided superior antithrombotic efficacy when compared with LMWH. In acute coronary syndromes, however, the antithrombotic activity of hirudin has been compromised by a significant increase in major hemorrhage.

Topics: Angina, Unstable; Anticoagulants; Clinical Trials as Topic; Fibrinolytic Agents; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Hirudin Therapy; Humans; Myocardial Infarction; Polysaccharides; Venous Thrombosis

Fondaparinux is an alternative to low molecular weight heparin (LMWH) for non-ST-elevation myocardial infarction (NSTEMI) with levels of recommendation that differ according to guidelines. The aim of this study was to assess outcomes in real world practice in NSTEMI patients participating in the French Registry of ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) 2010 according to the use of fondaparinux, in comparison with patients receiving enoxaparin.. FAST-MI 2010 is a nationwide French registry that included 4,169 patients with acute myocardial infarction at the end of 2010 in 213 centres (76% of active centres in France); 1,734 had NSTEMI, with 240 receiving fondaparinux and 1,027 enoxaparin. Patients receiving enoxaparin vs. fondaparinux had essentially characteristics with a similar GRACE (Global Registry of Acute Coronary Events) score. Invasive strategy was used in 69% in both groups. In-hospital bleeding was similar with both anticoagulant strategies and 1-year survival was 94.6% and 91.7%, respectively. Using fully adjusted Cox multivariate analysis, the use of fondaparinux was not associated with a reduced risk of death (hazard ratio: 1.35; 95% confidence interval: 0.70-2.51). After propensity score matching (207 patients per group), 1-year survival was similar with both strategies. There was, however, an interaction between fondaparinux and unfractionated heparin, with higher survival in fondaparinux-treated patients who received UFH, compared with those who did not.. In this French cohort of NSTEMI patients, predominantly managed invasively, there was no evidence that fondaparinux was superior to enoxaparin as regards bleeding events or 1-year mortality (FAST-MI 2010; NCT01237418).

Topics: Aged; Anticoagulants; Enoxaparin; Female; Fondaparinux; France; Heart Conduction System; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Polysaccharides; Prospective Studies; Registries; Treatment Outcome

Activated clotting time (ACT) is widely used to guide unfractionated heparin dosing during percutaneous coronary intervention. However, its value in predicting complications is controversial in the modern era. We sought to examine the relationship between ACT and outcomes in non-ST-segment-elevation acute coronary syndrome patients.. In the Fondaparinux With Unfractionated Heparin During Revascularization in Acute Coronary Syndromes (FUTURA/OASIS-8) trial, 2026 patients with non-ST-segment-elevation acute coronary syndrome treated with fondaparinux 2.5 mg/d and undergoing percutaneous coronary intervention were randomized to low-dose unfractionated heparin (50 U/kg) or standard-dose unfractionated heparin (85 U/kg or 60 U/kg with glycoprotein IIb/IIIa inhibitors, with ACT guidance). No difference was shown for major bleeding and there was a trend toward a reduction in ischemic events with standard-dose unfractionated heparin. To clarify the additional value of ACT guidance, we analyzed with logistic modeling peri-percutaneous coronary intervention outcomes according to peak ACT as a linear function. A threshold effect was then investigated. No linear correlation was found between ACT and thrombotic or bleeding events. In patients not receiving planned glycoprotein IIb/IIIa inhibitors, a significant increase in rates of death, myocardial infarction, and target vessel revascularization was identified in patients with an ACT≤300 s (4.86% versus 2.78%; adjusted odds ratio, 1.84; 95% confidence interval, 1.06-3.21; P=0.03). No threshold was found for hemorrhagic complications in patients with or without glycoprotein IIb/IIIa inhibitors.. Non-ST-segment-elevation acute coronary syndrome patients undergoing percutaneous coronary intervention with an ACT≤300 s are at increased risk of thrombotic complications. ACT, however, does not predict hemorrhagic complications.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00790907.

Topics: Aged; Female; Fondaparinux; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Polysaccharides; Postoperative Hemorrhage; Predictive Value of Tests; Prognosis; Thrombosis; Treatment Outcome; Whole Blood Coagulation Time

The echocardiographic substudy of the OASIS-6 trial evaluated the prognostic implications of left ventricle (LV) systolic and diastolic dysfunction early postacute ST-segment elevation myocardial infarction (STEMI) in patients treated with fondaparinux versus usual care.. Comprehensive echocardiograms were performed a median of 6 days after the index STEMI in 528 patients, 258 randomized to fondaparinux and 270 to usual care (unfractionated heparin or placebo), to assess LV systolic and diastolic function, LV mass, and LV end-systolic and end-diastolic volumes. A total of 245 (46.4%) patients were followed up for 3 months and 283 (53.6%) for 6 months. Major cardiac events (MACE) were defined as the composite of death, reinfarction, heart failure, or cardiogenic shock and resuscitated cardiac arrest.. Patients with LV ejection fraction (LVEF) ≤ 45% and restrictive diastolic function (RDF) were at greatly increased risk of MACE (hazard ratio [HR] = 8.85, 95% CI, 4.21–18.60) compared to patients with LVEF ≥ 45% and without RDF. RDF remained a strong predictor for MACE in patients with LVEF ≥ 45% (HR = 4.38, 95% CI, 1.52–12.60) and in multivariate models adjusted for LVEF, LV end-systolic volume, and clinical variables.. In this large international trial, LV systolic and diastolic function, as determined by echocardiography early following STEMI, are incremental predictors of MACE. In addition, RDF is a strong independent predictor of MACE after STEMI across a broad range of LVEF.

Topics: Anticoagulants; Diastole; Echocardiography; Electrocardiography; Female; Follow-Up Studies; Fondaparinux; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Polysaccharides; Predictive Value of Tests; Prognosis; Retrospective Studies; Systole; Ventricular Function, Left

The OASIS-6 trial demonstrated the benefit of fondaparinux in patients with ST-segment elevation myocardial infarction (STEMI) not undergoing primary percutaneous coronary intervention. Elderly compared to younger patients are at higher risk of bleeding and could have a different balance of benefits and risks when treated with antithrombotic therapy.. We explored the efficacy and safety of fondaparinux compared to control according to age tertiles in 12,092 patients with STEMI in the OASIS-6 trial. Death or myocardial infarction rates were reduced by fondaparinux in tertile I (age<56 years, 4.5% vs 4.8%, hazard ratio [HR] 0.94, 95% CI 0.71-1.25), in tertile II (age 56-68 years, 7.9% vs 9.7%, HR 0.80, 0.65-0.98), and in tertile III (age≥69 years, 17.2% vs 19.8%, HR 0.87, 95% CI 0.75-1.01, P for heterogeneity=0.87). Severe hemorrhage rates were reduced in tertile I (0.5% vs 0.6%, HR 0.94, 95% CI 0.41-2.12), in tertile II (0.9% vs 1.5%, HR 0.63, 95% CI 0.35-1.11), and in tertile III (2.1% vs 2.4%, HR 0.86, 95% CI 0.56-1.33, P for heterogeneity=0.86). Death, myocardial infarction, or severe hemorrhage rates were reduced in tertile I (4.8% vs 5.0%, HR 0.95, 95% CI 0.72-1.25), in tertile II (8.1% vs 10.1%, HR 0.79, 95% CI 0.65-0.97), and in tertile III (17.6% vs 20.4%, HR 0.86, 95% CI 0.74-1.00, P for heterogeneity=0.77).. The balance of benefits and risks of fondaparinux is consistent across age tertiles, supporting its use across the age spectrum of patients with STEMI who do not undergo primary percutaneous coronary intervention.

Topics: Aged; Anticoagulants; Coronary Angiography; Dose-Response Relationship, Drug; Electrocardiography; Factor X; Female; Follow-Up Studies; Fondaparinux; Humans; Male; Middle Aged; Myocardial Infarction; Polysaccharides; Syndrome; Treatment Outcome

Bleeding in patients with coronary artery disease has been linked with adverse outcomes. We examined the incidence and outcomes after bleeding in 20 078 patients with acute coronary syndromes (ACS) enrolled in the OASIS-5 trial who were treated with fondaparinux or the low-molecular weight heparin, enoxaparin.. Nine hundred and ninety (4.9%) patients developed major bleeding and 423 (2.1%) developed minor bleeding. Fondaparinux compared with enoxaparin reduced fatal bleeding [0.07 vs. 0.22%, relative risk (RR) 0.30, 95% CI: 0.13-0.71], non-fatal major bleeding (2.2 vs. 4.2%, RR 0.52, 95% CI: 0.44-0.61), minor bleeding (1.1 vs. 3.2%, RR 0.34, 95% CI: 0.27-0.42), and need for transfusion (1.8 vs. 3.1%, RR 0.56, 95% CI: 0.47-0.61) during the first 9 days. One of every six deaths during the first 30 days occurred in patients who experienced bleeding. Cox proportional hazards model revealed that major bleeding was associated with about a four-fold increased hazard of death, myocardial infarction, or stroke during the first 30 days and about a three-fold increased hazard during 180 days of follow up.. Bleeding in patients with ACS is a powerful determinant of fatal and non-fatal outcomes. Reducing the risk of bleeding using a safer anticoagulant strategy during the first 9 days is associated with substantial reductions in morbidity and mortality.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Enoxaparin; Female; Fondaparinux; Hemorrhage; Humans; Male; Myocardial Infarction; Myocardial Revascularization; Polysaccharides; Risk Factors; Stroke; Treatment Outcome

The Fifth and Sixth Organization to Assess Strategies in Ischemic Syndromes (OASIS 5 and 6) trials evaluated fondaparinux, a synthetic factor Xa inhibitor, in patients with non-ST- and ST-segment elevation acute coronary syndromes, respectively. Combined results for these 2 trials on major efficacy and safety outcomes and data on the effects of fondaparinux in relation to interventional management strategy have not been previously reported.. We performed an individual patient-level combined analysis of 26 512 patients from the OASIS 5 and 6 trials who were randomized in a double-blind fashion to fondaparinux 2.5 mg daily or a heparin-based strategy (dose-adjusted unfractionated heparin or enoxaparin). Results were stratified according to whether an early invasive, a delayed invasive, or an initial conservative management strategy was performed. Fondaparinux was superior to heparin in reducing the composite of death, myocardial infarction, or stroke (8.0% versus 7.2%; hazard ratio [HR], 0.91; P=0.03) and death alone (4.3% versus 3.8%; HR, 0.89; P=0.05). Fondaparinux reduced major bleeding by 41% (3.4% versus 2.1%; HR, 0.59; P<0.00001) and had a more favorable net clinical outcome than heparin (11.1% versus 9.3%; HR, 0.83; P<0.0001). In 19 085 patients treated with an invasive strategy, fondaparinux suppressed ischemic events to an extent similar to heparin and reduced major bleeding by more than one-half, resulting in a superior net clinical outcome (10.8% versus 9.4%; HR, 0.87; P=0.008). A similar benefit also was observed in those treated with a conservative strategy (HR, 0.74; 95% confidence interval, 0.64 to 0.85; P<0.001).. Compared with a heparin-based strategy, fondaparinux reduced mortality, ischemic events, and major bleeding across the full spectrum of acute coronary syndromes and was associated with a more favorable net clinical outcome in patients undergoing either an invasive or a conservative management strategy.

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Double-Blind Method; Drug Administration Schedule; Electrocardiography; Enoxaparin; Female; Fondaparinux; Hemorrhage; Heparin; Hospitalization; Humans; Male; Middle Aged; Myocardial Infarction; Polysaccharides; Stroke; Treatment Outcome

At least one quarter of ST-segment elevation myocardial infarction (STEMI) patients do not receive reperfusion therapy, and these patients are at high risk for new ischaemic events. We evaluated fondaparinux treatment vs. usual care, i.e. placebo or unfractionated (UF) heparin, in a pre-specified subgroup of 2867 (out of 12 092) patients not receiving reperfusion treatment in the OASIS-6 trial.. In all, 1458 patients were randomized to fondaparinux 2.5 mg once daily subcutaneously up to 8 days and 1409 patients to usual care (control). Randomization was stratified by indication for UF heparin (stratum II, n = 1226) or not (stratum I, n = 1641) based on the investigator's judgment.. The proportion of patients who suffered death or myocardial re-infarction at 30 days (primary outcome) was 12.2% in the fondaparinux vs. 15.1% in the control group, hazard ratio (HR) 0.80; 95% confidence interval (CI) 0.65-0.98. There was no increase in severe bleedings, HR 0.82; CI 0.44-1.55, or strokes, HR 0.62; CI 0.29-1.33. Consequently, the composite of death, myocardial re-infarction, or severe bleeding were significantly reduced at 30 days, HR 0.81; CI 0.67-0.99. Reductions in death or myocardial re-infarction at 30 days were consistent in stratum I with fondaparinux vs. placebo, HR 0.88; 95% CI 0.65-1.19, and in stratum II with fondaparinux vs. UF heparin infusion for 24-48 h (n = 806), HR 0.74; CI 95% 0.57-0.97, P = 0.41 for heterogeneity.. In STEMI patients not receiving reperfusion treatment, fondaparinux reduces the composite of death or myocardial re-infarction without an increase in severe bleedings or strokes as compared to placebo or UF heparin.

Topics: Aged; Anticoagulants; Double-Blind Method; Female; Fondaparinux; Hemorrhage; Heparin; Humans; Male; Myocardial Infarction; Polysaccharides; Secondary Prevention; Survival Analysis; Time Factors

No antithrombotic therapy has been shown to reduce mortality when used with thrombolytics in acute myocardial infarction (AMI). In the OASIS-6 trial, fondaparinux significantly reduced mortality and reinfarction without increasing bleeding in 12 092 patients with acute ST elevation MI.. We report the results of a subgroup analysis in the 5436 patients (45%) receiving thrombolytics. According to local practice, 4415 patients did not have an indication for unfractionated heparin (stratum 1) and 1021 did (stratum 2). Fondaparinux reduced the primary study outcome of death or MI at 30 days [Hazard ratio (HR) 0.79, 95% confidence interval (CI) 0.68-0.92] with consistent reductions in both mortality (HR and CI) and reinfarction (HR and CI). There was a non-significantly lower rate of stroke (HR 0.77, CI 0.48-1.25). The risk of severe bleeding was significantly reduced (HR 0.62, CI 0.40-0.94), and thus the balance of benefit and risk (death, MI and severe haemorrhage) was clearly reduced by fondaparinux (HR 0.77, 95% CI 0.67-0.90). Results were consistent in the two strata, by the different types of thrombolytics and across various time intervals from symptom onset to treatment.. In STEMI patients treated with thrombolytic agents (predominantly streptokinase), fondaparinux significantly reduced the risk of death, re-MI and severe bleeds.

Topics: Anticoagulants; Female; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Polysaccharides; Randomized Controlled Trials as Topic; Risk Factors; Secondary Prevention; Survival Analysis; Time Factors; Treatment Outcome

A recent randomized, controlled trial, the Fifth Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS 5) trial, reported that major bleeding was 2-fold less frequent with fondaparinux than with enoxaparin in acute coronary syndromes (ACS). Renal dysfunction increases the risk for major bleeding.. To compare the efficacy and safety of fondaparinux and enoxaparin over the spectrum of renal dysfunction observed in the OASIS 5 trial.. Subgroup analysis of a randomized, controlled trial.. Patients presenting to the hospital with non-ST-segment elevation ACS.. 19,979 of the 20,078 patients in the OASIS 5 trial in whom creatinine was measured at baseline.. Death, myocardial infarction, refractory ischemia, and major bleeding were evaluated separately and as a composite end point at 9, 30, and 180 days. Glomerular filtration rate (GFR) was calculated by using the Modification of Diet in Renal Disease formula.. The absolute differences in favor of fondaparinux (efficacy and safety) were most marked in patients with a GFR less than 58 mL/min per 1.73 m2; the largest differences occurred in major bleeding events. At 9 days, death, myocardial infarction, or refractory ischemia occurred in 6.7% of patients receiving fondaparinux and 7.4% of those receiving enoxaparin (hazard ratio, 0.90 [95% CI, 0.73 to 1.11]); major bleeding occurred in 2.8% and 6.4%, respectively (hazard ratio, 0.42 [CI, 0.32 to 0.56]). Statistically significant differences in major bleeding persisted at 30 and 180 days. The rates of the composite end point were lower with fondaparinux than with enoxaparin in all quartiles of GFR, but the differences were statistically significant only among patients with a GFR less than 58 mL/min per 1.73 m2.. Subgroup analyses warrant caution; the study was powered to detect noninferiority at 9 days. Fondaparinux is not approved for use in patients with ACS in the United States.. The benefits of fondaparinux over enoxaparin when administered for non-ST-segment elevation ACS are most marked among patients with renal dysfunction and are largely explained by lower rates of major bleeding with fondaparinux.

Topics: Aged; Aged, 80 and over; Angina Pectoris; Anticoagulants; Coronary Disease; Death, Sudden, Cardiac; Double-Blind Method; Enoxaparin; Female; Fondaparinux; Glomerular Filtration Rate; Hemorrhage; Humans; Kidney; Male; Middle Aged; Myocardial Infarction; Polysaccharides; Syndrome

This study reports a prospectively planned analysis of patients with acute coronary syndrome who underwent early percutaneous coronary intervention (PCI) in the OASIS-5 (Fifth Organization to Assess Strategies in Ischemic Syndromes) trial.. In the OASIS-5 trial, fondaparinux was similar to enoxaparin for short-term efficacy, but reduced major bleeding by one-half and 30-day mortality by 17%.. The OASIS-5 trial was a double-blind, randomized comparison of fondaparinux and enoxaparin in 20,078 patients with acute coronary syndrome. A total of 12,715 patients underwent heart catheterization during the initial hospitalization, and 6,238 patients underwent PCI. In the fondaparinux group, intravenous fondaparinux was given for PCI. In the enoxaparin group, no additional anticoagulant was given if PCI was <6 h from last subcutaneous dose, and additional intravenous unfractionated heparin (UFH) was given if PCI was >6 h.. Fondaparinux compared with enoxaparin reduced major bleeding by more than one-half (2.4% vs. 5.1%, hazard ratio [HR] 0.46, p < 0.00001) at day 9, with similar rates of ischemic events, resulting in superior net clinical benefit (death, myocardial infarction, stroke, major bleeding: 8.2% vs. 10.4%, HR 0.78, p = 0.004). Fondaparinux reduced major bleeding 48 h after PCI irrespective of whether PCI was performed <6 h of the last enoxaparin dose (1.6% vs. 3.8%, HR 0.42, p < 0.0001) or >6 h when UFH was given (1.3% vs. 3.4%, HR 0.39, p < 0.0001). Catheter thrombus was more common in patients receiving fondaparinux (0.9%) than enoxaparin alone (0.4%), but was largely prevented by using UFH at the time of PCI, without any increase in bleeding.. Upstream therapy with fondaparinux compared with upstream enoxaparin substantially reduces major bleeding while maintaining efficacy, resulting in superior net clinical benefit. The use of standard UFH in place of fondaparinux at the time of PCI seems to prevent angiographic complications, including catheter thrombus, without compromising the benefits of upstream fondaparinux.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Cohort Studies; Double-Blind Method; Enoxaparin; Female; Fondaparinux; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Polysaccharides; Syndrome; Time Factors; Treatment Outcome

The combined use of anticoagulants, antiplatelet agents, and invasive coronary procedures reduces ischemic coronary events but also increases bleeding in patients with acute coronary syndromes. We therefore assessed whether fondaparinux would preserve the anti-ischemic benefits of enoxaparin while reducing bleeding.. We randomly assigned 20,078 patients with acute coronary syndromes to receive either fondaparinux (2.5 mg daily) or enoxaparin (1 mg per kilogram of body weight twice daily) for a mean of six days and evaluated death, myocardial infarction, or refractory ischemia at nine days (the primary outcome); major bleeding; and their combination. Patients were followed for up to six months.. The number of patients with primary-outcome events was similar in the two groups (579 with fondaparinux [5.8 percent] vs. 573 with enoxaparin [5.7 percent]; hazard ratio in the fondaparinux group, 1.01; 95 percent confidence interval, 0.90 to 1.13), satisfying the noninferiority criteria. The number of events meeting this combined outcome showed a nonsignificant trend toward a lower value in the fondaparinux group at 30 days (805 vs. 864, P=0.13) and at the end of the study (1222 vs. 1308, P=0.06). The rate of major bleeding at nine days was markedly lower with fondaparinux than with enoxaparin (217 events [2.2 percent] vs. 412 events [4.1 percent]; hazard ratio, 0.52; P<0.001). The composite of the primary outcome and major bleeding at nine days favored fondaparinux (737 events [7.3 percent] vs. 905 events [9.0 percent]; hazard ratio, 0.81; P<0.001). Fondaparinux was associated with a significantly reduced number of deaths at 30 days (295 vs. 352, P=0.02) and at 180 days (574 vs. 638, P=0.05).. Fondaparinux is similar to enoxaparin in reducing the risk of ischemic events at nine days, but it substantially reduces major bleeding and improves long term mortality and morbidity. (ClinicalTrials.gov number, NCT00139815.).

Topics: Aged; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Enoxaparin; Female; Fondaparinux; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Polysaccharides; Recurrence; Stroke; Survival Analysis; Treatment Outcome

Despite many therapeutic advances, mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) remains high. The role of additional antithrombotic agents is unclear, especially among patients not receiving reperfusion therapy.. To evaluate the effect of fondaparinux, a factor Xa inhibitor, when initiated early and given for up to 8 days vs usual care (placebo in those in whom unfractionated heparin [UFH] is not indicated [stratum 1] or unfractionated heparin for up to 48 hours followed by placebo for up to 8 days [stratum 2]) in patients with STEMI.. Randomized double-blind comparison of fondaparinux 2.5 mg once daily or control for up to 8 days in 12,092 patients with STEMI from 447 hospitals in 41 countries (September 2003-January 2006). From day 3 through day 9, all patients received either fondaparinux or placebo according to the original randomized assignment.. Composite of death or reinfarction at 30 days (primary) with secondary assessments at 9 days and at final follow-up (3 or 6 months).. Death or reinfarction at 30 days was significantly reduced from 677 (11.2%) of 6056 patients in the control group to 585 (9.7%) of 6036 patients in the fondaparinux group (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.77-0.96; P = .008); absolute risk reduction, 1.5%; 95% CI, 0.4%-2.6%). These benefits were observed at 9 days (537 [8.9%] placebo vs 444 [7.4%] fondaparinux; HR, 0.83; 95% CI, 0.73-0.94; P = .003, and at study end (857 [14.8%] placebo vs 756 [13.4%] fondaparinux; HR, 0.88; 95% CI, 0.79-0.97; P = .008). Mortality was significantly reduced throughout the study. There was no heterogeneity of the effects of fondaparinux in the 2 strata by planned heparin use. However, there was no benefit in those undergoing primary percutaneous coronary intervention. In other patients in stratum 2, fondaparinux was superior to unfractionated heparin in preventing death or reinfarction at 30 days (HR, 0.82; 95% CI, 0.66-1.02; P = .08) and at study end (HR, 0.77; 95% CI, 0.64-0.93; P = .008). Significant benefits were observed in those receiving thrombolytic therapy (HR, 0.79; P = .003) and those not receiving any reperfusion therapy (HR, 0.80; P = .03). There was a tendency to fewer severe bleeds (79 for placebo vs 61 for fondaparinux; P = .13), with significantly fewer cardiac tamponade (48 vs 28; P = .02) with fondaparinux at 9 days.. In patients with STEMI, particularly those not undergoing primary percutaneous coronary intervention, fondaparinux significantly reduces mortality and reinfarction without increasing bleeding and strokes.. ClinicalTrials.gov Identifier NCT00064428.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Double-Blind Method; Factor X; Female; Fondaparinux; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Polysaccharides; Recurrence; Risk Assessment; Survival Analysis

Factor Xa plays a central role in the generation of thrombin, making it a novel target for treatment of arterial thrombosis. Fondaparinux is a synthetic factor Xa inhibitor that has been shown to be superior to standard therapies for the prevention of venous thrombosis. We performed a randomized trial to determine the safety and feasibility of fondaparinux in the percutaneous coronary intervention (PCI) setting.. A total of 350 patients undergoing elective or urgent PCI were randomized in a blinded manner to receive unfractionated heparin (UFH), 2.5 mg fondaparinux IV, or 5.0 mg fondaparinux IV. Randomization was stratified for planned or no planned use of glycoprotein (GP) IIb/IIIa antagonists. The primary safety outcome was total bleeding, which was a combination of major and minor bleeding events. The incidence of total bleeding was 7.7% in the UFH group and 6.4% in the combined fondaparinux groups (hazard ratio, 0.81; 95% confidence interval, 0.35 to 1.84; P=0.61). Bleeding was less common in the 2.5-mg fondaparinux group compared with the 5-mg fondaparinux group (3.4% versus 9.6%, P=0.06). The composite efficacy outcome of all-cause mortality, myocardial infarction, urgent revascularization, or need for a bailout GPIIb/IIIa antagonist was 6.0% in the UFH group and 6.0% in the fondaparinux group, with no significant difference in efficacy among the fondaparinux doses compared with UFH. Coagulation marker analysis at 6 and 12 hours after PCI demonstrated that fondaparinux was superior to UFH in inducing a sustained reduction in markers of thrombin generation, as measured by prothrombin fragment F1.2 (P=0.02).. In this pilot study of patients undergoing contemporary PCI, factor Xa inhibition with the synthetic anticoagulant fondaparinux in doses of 2.5 and 5.0 mg was comparable to UFH for clinical safety and efficacy outcomes. These data form the basis for further evaluation of fondaparinux in arterial thrombosis.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Emergencies; Factor Xa Inhibitors; Feasibility Studies; Female; Fondaparinux; Hemorrhage; Heparin; Hospital Mortality; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Pilot Projects; Polysaccharides; Single-Blind Method; Stents; Treatment Outcome

Factor Xa plays a central role in the generation of thrombin, making it a novel target for treatment of arterial thrombosis. Fondaparinux, a synthetic pentasaccharide, is a factor Xa inhibitor, which has been shown to be superior to enoxaparin for the prevention of venous thrombosis. We designed a large, phase III, randomized trial to evaluate the efficacy and safety of fondaparinux compared with enoxaparin in acute coronary syndromes.. The OASIS-5 trial is a randomized, double-blind trial of fondaparinux versus enoxaparin in 20,000 patients with unstable angina or non-ST-segment elevation myocardial infarction. The primary objective is to determine whether fondaparinux is noninferior to enoxaparin in preventing the composite of death, new myocardial infarction, and refractory ischemia at 9 days (primary outcome) and at 30 days (secondary outcome) after randomization. There will be additional follow-up of all patients for 3 to 6 months after randomization. If noninferiority is established at 9 days, superiority will be tested. The primary safety outcome is to evaluate the rates of major bleeds in the 2 groups with the balance of benefit and risk assessed by comparing the impact on the composite of the primary and safety outcomes. Secondary outcomes are each component of the composite primary outcome separately at days 9, 30, and up to 6 months. The TIMACS, a major substudy using a partial 2x2 factorial design evaluating whether early angiography and intervention (within 24 hours) are superior to a more delayed approach (after 36 hours) in reducing major ischemic events at 6 months after randomization.. The MICHELANGELO OASIS 5 program will provide a comprehensive and reliable evaluation of fondaparinux in a broad spectrum of patients with ACS.

Topics: Acute Disease; Aged; Angina, Unstable; Anticoagulants; Coronary Disease; Double-Blind Method; Enoxaparin; Female; Fondaparinux; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Patient Selection; Polysaccharides

Aim      To study specific features of the parenteral anticoagulant therapy for acute myocardial infarction (MI) in the Russian Federation and to evaluate the consistency of the prescribed parenteral anticoagulant therapy with the effective clinical guidelines.Material and methods  REGION-MI, the Russian rEGIstry for acute myOcardial iNfarction, is a multicenter observational study. This registry includes all patients admitted to hospitals with a documented diagnosis of ST-elevation acute MI (STEMI) and non-ST-elevation acute MI (NSTEMI) based on the criteria of the Forth Universal Definition of MI of the European Society of Cardiology. Risk of bleeding was assessed with the Academic Research Consortium for High Bleeding Risk (ARC-HBR) scale, and risk of major bleeding in patients with NSTEMI was additionally assessed with the CRUSADE scale.Results From November 01, 2020 through April 03, 2022, 5025 patients were included into the REGION-MI registry. At primary vascular departments, 70.5% of patients were administered unfractionated heparin (NFH); at regional vascular centers, 37.1 % of patients were administered NFH, 29.6 % enoxaparin, 20,2% NFH in combination with enoxaparin, 6.8 % fondaparinux, 4.2 % NFH in combination with fondaparinux, and 1.9 % nadroparin. At the prehospital stage, NFH was used as an anticoagulant support for the thrombolytic therapy (TLT) in 84% of patients, and low-molecular heparins (LMH) were used in 16 %. At the hospital stage, UFH was administered to 64.4 % of patients, and enoxaparin was administered to 23.9 % of patients. Among the patients who had undergone primary percutaneous coronary intervention (PCI), 40 % received NFH, 25 % enoxaparin, 22 % NFH in combination with enoxaparin, 7 % fondaparinux, and 4 % NFH in combination with fondaparinux. In conservative and invasive tactics of therapy for NSTEMI, NFH was also administered more frequently (43 and 43 %, respectively), followed by (according to frequency of administration) enoxaparin (36 and 34 %, respectively), NFH in combination with enoxaparin (10 and 16 %, respectively), fondaparinux (7 and 6 %, respectively), and NFH in combination with fondaparinux (3 and 1 %, respectively).Conclusion      According to the Russian registry of acute MI, REGION-MI, with all strategies for the treatment of MI, parenteral anticoagulants are not prescribed in full consistency with clinical guidelines. The most frequently used parenteral anticoagulant is NFH. Despite the high efficacy a

Topics: Anticoagulants; Enoxaparin; Fondaparinux; Hemorrhage; Heparin; Humans; Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Percutaneous Coronary Intervention; ST Elevation Myocardial Infarction; Treatment Outcome

There is no specific evidence on the antithrombotic management of survivors of out-of-hospital cardiac arrest (OHCA) due to acute myocardial infarction (AMI). We sought to compare the short-term outcome of unfractioned heparin (UFH) vs fondaparinux in OHCA survivors due to AMI admitted in our Institution in the last decade.. We performed a retrospective cohort study on survivors of OHCA due to AMI managed with UFH or fondaparinux during the hospitalization. The primary outcome was the occurrence of any bleeding, all-cause mortality, cerebrovascular accidents, re-MI, and unplanned revascularization at 1 month. A propensity-score matching was performed to compare the outcome between UFH and fondaparinux.. Out of 2083 AMI patients undergoing successful PCI, OHCA was present in 94 (4.5%): 41 (43.6%) treated with UFH and 53 (56.4%) with fondaparinux. At clinical follow-up, the incidence of the primary outcome was 65.9% in UFH and 35.8% in fondaparinux group (p = 0.007). More than half of the events included in the primary outcome were related to bleeding complications. In the matched cohort of 56 patients, the primary outcome occurred in 46.4% and 25.0% (p = 0.16), while bleeding was present in 32.1% and 7.1% (p = 0.04), in the UFH and fondaparinux group, respectively.. The present analysis suggests that fondaparinux is safer than UFH in the management of OHCA due to AMI by reducing early bleeding complications at one month.

Topics: Anticoagulants; Fondaparinux; Hemorrhage; Heparin; Humans; Myocardial Infarction; Out-of-Hospital Cardiac Arrest; Percutaneous Coronary Intervention; Retrospective Studies

Although anticoagulation with unfractionated heparin (UFH) is commonly used during intra-aortic balloon pump (IABP) counterpulsation to prevent thromboembolic events, no data or guidelines exist to support this strategy, especially in the setting of acute myocardial infarction (AMI). This study sought to compare the short-term outcome of UFH vs fondaparinux in AMI patients who underwent successful percutaneous coronary intervention (PCI) and IABP insertion.. The anticoagulation therapy of revascularised AMI patients who received IABP counterpulsation and admitted to a tertiary hospital in the last decade was retrospectively evaluated. The primary outcome was the occurrence of all-cause mortality, stroke or transient ischaemic attack, reinfarction, unplanned revascularisation, major or minor limb ischaemia, and any bleeding at 1 month. Propensity score matching was performed to compare the primary outcome between UFH and fondaparinux.. Of 1,355 AMI survivors at 2 days after hospital admission and who underwent successful PCI, an IABP was inserted in 197 (14.5%): 72 (36.5%) were treated with UFH and 125 (63.5%) with fondaparinux (2.5 mg o.d.). At clinical follow-up, completed in 98.5% of cases, the incidence of the primary outcome was 22.5% in UFH and 5.7% in fondaparinux groups (p=0.0009). More than two-thirds of the events included in the primary outcome were related to early bleeding complications. In the matched cohort of 62 patients, the primary outcome occurred in 14 (45.2%) patients in the UFH and two (6.5%) in the fondaparinux group (p=0.01).. This study suggested that fondaparinux is safer, by reducing early bleeding complications at one month, than UFH in the management of IABP.

Topics: Fondaparinux; Heparin; Humans; Intra-Aortic Balloon Pumping; Myocardial Infarction; Percutaneous Coronary Intervention; Retrospective Studies; Shock, Cardiogenic; Treatment Outcome

Our previous study showed that parenteral anticoagulation therapy (PACT) in the context of aggressive antiplatelet therapy failed to improve clinical outcomes in patients undergoing percutaneous coronary intervention for non-ST-segment elevation acute coronary syndrome (NSTE-ACS). However, the role of PACT in patients managed medically remains unknown. This observational cohort study enrolled patients with NSTE-ACS receiving medical therapy from November 2014 to June 2017 in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project. Eligible patients were included in the PACT group and non-PACT group. The primary outcomes were in-hospital all-cause mortality and major bleeding. The secondary outcome included minor bleeding. Among 23,726 patients, 8,845 eligible patients who received medical therapy were enrolled. After adjusting the potential confounders, PACT was not associated with a lower risk of in-hospital all-cause mortality (adjusted odds ratio (OR), 1.25; 95% confidence interval (CI), 0.92-1.71; P = 0.151). Additionally, PACT did not increase the incidence of major bleeding or minor bleeding (major bleeding: adjusted OR, 1.04; 95% CI, 0.80-1.35; P = 0.763; minor bleeding: adjusted OR, 1.27; 95% CI, 0.91-1.75; P = 0.156). The propensity score analysis confirmed the primary analyses. In patients with NSTE-ACS receiving antiplatelet therapy, PACT was not associated with a lower risk of in-hospital all-cause mortality or a higher bleeding risk in patients with NSTE-ACS receiving non-invasive therapies and concurrent antiplatelet strategies. Randomized clinical trials are warranted to reevaluate the safety and efficacy of PACT in all patients with NSTE-ACS who receive noninvasive therapies and current antithrombotic strategies.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Angina, Unstable; Anticoagulants; China; Dual Anti-Platelet Therapy; Female; Fondaparinux; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hospital Mortality; Humans; Infusions, Parenteral; Injections; Ischemic Stroke; Male; Middle Aged; Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Recurrence

Fondaparinux (FDX) was demonstrated to be cardioprotective in a rat model of myocardial ischemia reperfusion. In this model, FDX reduced infarct size after 2h of reperfusion, involving the activation of the survivor activating factor enhancement (SAFE) pathway as early as 30min post-reperfusion. Our aim was to study if this cardioprotection could be explained by anti-inflammatory mechanisms and a protective effect on vessels.. Wistar male rats were subjected to 40minutes (min) of myocardial ischemia, followed by 30min or 2h of reperfusion. Rats were randomized into four groups: control 30min (n=7), FDX 30min (n=7), control 2h (n=7), and FDX 2h (n=7). The FDX groups received 10mg/kg injection of FDX 10min prior to initiating reperfusion. We studied: 1) mRNA expression of endothelial markers, such as thrombomodulin (TM), endothelial protein C receptor (EPCR), and tissue factor (TF) and 2) proteic expression of ICAM-1, NF-κB, IκB, and JNK. Leukocyte infiltration was assessed by histochemistry. We also evaluated TM and EPCR mRNA expression in a model of isolated rat mesenteric arteries incubated with FDX.. FDX upregulated the expression of TM and EPCR mRNA in the models of myocardial infarction and isolated mesenteric arteries. No difference was observed between the treated and control groups regarding the expression of pro-inflammatory signaling proteins, adhesion molecules, and leukocyte infiltration after 2h of reperfusion.. The cardioprotective effect of FDX at early-stage reperfusion could be related to vascular protection, yet not to an anti-inflammatory effect.

Topics: Animals; Anticoagulants; Cardiotonic Agents; Disease Models, Animal; Fondaparinux; Male; Mesenteric Arteries; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Polysaccharides; Rats; Rats, Wistar; Receptors, Endothelin; RNA, Messenger; Thrombomodulin; Up-Regulation

Fondaparinux was associated with reduced major bleeding events and improved survival compared with low-molecular-weight heparin (LMWH) in a large randomized clinical trial involving patients with non-ST-segment elevation myocardial infarction (NSTEMI). Large-scale experience of the use of fondaparinux vs LMWH in a nontrial setting is lacking.. To study the association between the use of fondaparinux vs LMWH and outcomes in patients with NSTEMI in Sweden.. Prospective multicenter cohort study from the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies registry involving 40,616 consecutive patients with NSTEMI who received fondaparinux or LMWH between September 1, 2006, through June 30, 2010, with the last follow-up on December 31, 2010.. In-hospital treatment with fondaparinux or LMWH during the hospital stay.. In-hospital severe bleeding events and death and 30- and 180-day death, MI, stroke, and major bleeding events. Logistic regression models adjusted for calendar time, admitting hospital, baseline characteristics, and in-hospital revascularization.. In total, 14,791 patients (36.4%) were treated with fondaparinux and 25,825 (63.6%) with LMWH. One hundred sixty-five patients (1.1%) in the fondaparinux group vs 461 patients (1.8%) in the LMWH group experienced in-hospital bleeding events (adjusted odds ratio [OR], 0.54; 95% CI, 0.42-0.70). A total of 394 patients (2.7%) in the fondaparinux group died while in the hospital vs 1022 (4.0%) in the LMWH group (adjusted OR, 0.75; 95% CI, 0.63-0.89). The differences in major bleeding events and mortality between the 2 treatments were similar at 30 and 180 days. There were no significant differences in the number of recurrent MI and stroke events at 30 or 180 days among the 2 treatment groups.. In routine clinical care of patients with NSTEMI, fondaparinux was associated with lower odds than LMWH of major bleeding events and death both in-hospital and up to 180 days afterward.

Topics: Aged; Cardiovascular Diseases; Cohort Studies; Electrocardiography; Female; Fondaparinux; Glomerular Filtration Rate; Hemorrhage; Heparin, Low-Molecular-Weight; Hospital Mortality; Humans; Kidney Diseases; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Polysaccharides; Registries; Sweden

Acute myocardial infarction is a leading cause of mortality and morbidity worldwide. Although essential for successful recovery, myocardium reperfusion is associated with reperfusion injury. Two major cell survival signaling cascades are known to be protective against ischemia-reperfusion (I/R) injury: the reperfusion injury salvage kinase, including Akt, extracellular signal-regulated kinase 1/2, and the downstream target GSK-3β, and the survivor activating factor enhancement, which involves STAT-3. Pharmacologic inhibition of factor Xa has been shown to attenuate I/R injury, but the cellular mechanism is poorly understood. Our aim was to determine the role of whole blood in fondaparinux (FDX)-induced cardioprotection and the involvement of reperfusion injury salvage kinase and survivor activating factor enhancement pathways. We investigated FDX ability to prevent in vivo I/R injury using a transient coronary ligation rat model and ex vivo using a model of crystalloid-perfused isolated rat heart. In both models, infarct size was assessed after 120 min of reperfusion. Myocardial tissues were collected after 15 and 30 min of reperfusion for Western blot analysis. In vivo, FDX decreased infarct size by 29% and induced significant STAT-3 and GSK-3β phosphorylation in comparison to controls. Adding AG490, an inhibitor of JAK/STAT pathway, before I/R, prevented STAT-3 phosphorylation and abolished FDX-induced cardioprotection. On the contrary, FDX did not have an effect on infarct size or hemodynamic parameters in the isolated-heart model. Fondaparinux decreased I/R injury in vivo, but not in a crystalloid-perfused isolated heart. Under our experimental conditions, FDX required whole blood to be protective, and this beneficial effect was mediated through STAT-3 phosphorylation.

Topics: Animals; Cardiotonic Agents; Fondaparinux; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; In Vitro Techniques; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Polysaccharides; Rats; STAT3 Transcription Factor; Tyrphostins

Fondaparinux is an indirect, Factor Xa inhibitor that requires co-administration of another anticoagulant with anti-Factor IIa activity for percutaneous coronary intervention (PCI) per guideline recommendations. In this setting, the use of bivalirudin, a direct Factor IIa inhibitor, is not well established.. Using the Premier hospital database, we identified 971 patients who underwent elective or urgent PCI after receiving fondaparinux as the initial anticoagulant. They were treated with either bivalirudin ± glycoprotein IIb/IIIa inhibitor (GPI) (Group A=618) or unfractionated heparin (UFH) ± GPI (Group B=353) during PCI. A 2:1 propensity score matching (PSM) process was performed to control for patient and hospital level characteristics. The primary endpoints were to determine in-hospital death, bleeding and post-PCI length of stay (LOS) between treatment groups. After PSM, 512 matched patients were analysed (Group A=348 and Group B=174). In-hospital death was 1.4% in Group A vs. 2.9% in Group B (p=0.26). Clinically apparent bleeding occurred in 4.0% of Group A vs. 9.2% of Group B patients (p<0.02). Clinically apparent bleeding requiring transfusion was lower in Group A patients (0.6% vs. 2.9%; p=0.04). Post-PCI LOS was 1.9 ± 3.8 days for Group A and 2.4 ± 5.8 days for Group B (p=0.36). GPI use during PCI occurred in 9.2% of Group A vs. 44.8% of Group B patients (p<0.0001).. After initial administration of fondaparinux, a bivalirudin-based strategy for PCI is associated with significantly reduced bleeding, with similar mortality and post-PCI LOS when compared with an UFH-based strategy.

Topics: Aged; Anticoagulants; Antithrombins; Drug Therapy, Combination; Female; Follow-Up Studies; Fondaparinux; Hemorrhage; Heparin; Hirudins; Hospital Mortality; Humans; Incidence; Length of Stay; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Polysaccharides; Prospective Studies; Recombinant Proteins; Retrospective Studies; Treatment Outcome

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

The 'pill in the pocket' concept is an established therapy for atrial fibrillation. The current guidelines for the management of patients with ST-elevation myocardial infarction endorse the concept that faster time to reperfusion is associated with important reductions in morbidity and mortality. The mechanical reperfusion and outcome of these patients is significantly supported by dual antiplatelet therapy. There is no data comparing the effect of early self-application by the patient ('pill in the pocket') versus application by the emergency doctor of dual antiplatelet therapy and a factor Xa inhibitor in case of severe chest pain. In patients with a high risk of developing an acute coronary syndrome and previously selected by a cardiologist, early self-application of dual antiplatelet therapy and a factor Xa inhibitor (e.g. fondaparinux) immediately after calling the emergency doctor might be of significance in cases of acute coronary syndrome or pulmonary embolism. In particular, in less developed areas where it might take a long time for the emergency doctor to arrive, this 'pill in the pocket' concept may be significant.

Topics: Acute Coronary Syndrome; Anticoagulants; Drug Therapy, Combination; Emergency Medical Services; Factor Xa Inhibitors; Fondaparinux; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Polysaccharides; Self Administration

Anticoagulant therapy is widely used for the management of acute coronary syndromes. In order to optimize patient outcomes, anticoagulants should ideally combine high antithrombotic efficacy with a low risk of bleeding. Intravenous unfractionated heparin has been in clinical use for more than 50 years and reduces the risk of recurrent ischemic events in patients with acute coronary syndromes but at the cost of increased bleeding. Enoxaparin, compared with intravenous unfractionated heparin, further reduces the risk of ischemic events but also increases bleeding. Neither of these approaches has been shown to reduce mortality. The synthetic parenteral Factor Xa inhibitor, fondaparinux, is highly effective for the prevention and treatment of venous thromboembolic disease in medical and surgical patients. The Organization for the Assessment of Strategies for Ischemic Syndromes (OASIS) 5 and 6 trials evaluated the efficacy and safety of fondaparinux in more than 32,000 patients with non-ST elevation acute coronary syndromes or ST elevation myocardial infarction. This clinical trial report discusses the findings of these two pivotal trials.

Topics: Acute Coronary Syndrome; Anticoagulants; Double-Blind Method; Enoxaparin; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Humans; Middle Aged; Myocardial Infarction; Polysaccharides; Randomized Controlled Trials as Topic

This article about hemorrhagic complications of anticoagulant and thrombolytic treatment is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Bleeding is the major complication of anticoagulant and fibrinolytic therapy. The criteria for defining the severity of bleeding vary considerably between studies, accounting in part for the variation in the rates of bleeding reported. The major determinants of vitamin K antagonist (VKA)-induced bleeding are the intensity of the anticoagulant effect, underlying patient characteristics, and the length of therapy. There is good evidence that VKA therapy, targeted international normalized ratio (INR) of 2.5 (range, 2.0-3.0), is associated with a lower risk of bleeding than therapy targeted at an INR > 3.0. The risk of bleeding associated with IV unfractionated heparin (UFH) in patients with acute venous thromboembolism is < 3% in recent trials. This bleeding risk may increase with increasing heparin dosages and age (> 70 years). Low-molecular-weight heparin (LMWH) is associated with less major bleeding compared with UFH in acute venous thromboembolism. Higher doses of UFH and LMWH are associated with important increases in major bleeding in ischemic stroke. In ST-segment elevation myocardial infarction, addition of LMWH, hirudin, or its derivatives to thrombolytic therapy is associated with a small increase in the risk of major bleeding, whereas treatment with fondaparinux or UFH is associated with a lower risk of bleeding. Thrombolytic therapy increases the risk of major bleeding 1.5-fold to threefold in patients with acute venous thromboembolism, ischemic stroke, or ST-elevation myocardial infarction.

Topics: Anticoagulants; Brain Ischemia; Evidence-Based Medicine; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Hirudins; Humans; International Normalized Ratio; Myocardial Infarction; Polysaccharides; Risk Factors; Severity of Illness Index; Thrombolytic Therapy; Treatment Outcome; Venous Thromboembolism; Vitamin K

To summarize key changes in the 2007 American College of Cardiology/American Heart Association (ACC/AHA) guideline recommendations for pharmacologic therapy as they relate to antiplatelets and anticoagulants, and to evaluate the evidence from several landmark trials that was used to support the guideline updates for these agents.. Literature was accessed through MEDLINE (1950-January 2008) using the search terms acute coronary syndromes, unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), antiplatelet, and anticoagulant. All papers were cross-referenced to identify additional studies.. ACC/AHA guidelines, relevant original research articles, and review articles were evaluated. Studies with more than 1000 patients were the focus of the review.. UA and NSTEMI are the most common presentations of acute coronary syndrome. The recently updated ACC/AHA guidelines for management of this condition were based on significant advances in pharmacotherapy including expanded use of drug-eluting stents, pretreatment with clopidogrel, and newer anticoagulants such as bivalirudin and fondaparinux. Landmark trials have been published that describe advances in the use of antiplatelets and anticoagulants. According to the guidelines, unfractionated heparin (UFH) and enoxaparin are preferred options for both invasive and conservative management. Enoxaparin was noninferior to UFH for invasive management in the SYNERGY trial, although it was associated with a higher incidence of bleeding. Other alternatives for an invasive strategy per the guidelines include bivalirudin and fondaparinux. Bivalirudin (alone or with glycoprotein [GP] IIb/IIIa inhibitor) was compared with heparin plus GP IIb/IIIa inhibitor in the ACUITY trial of patients undergoing early invasive management. The bivalirudin groups were noninferior to standard of care, although bivalirudin alone was associated with less bleeding. Fondaparinux was found to be noninferior to enoxaparin and was associated with fewer bleeding events in the OASIS-5 study of patients who were not treated with an early invasive approach. Accordingly, the guidelines 1list fondaparinux as an alternative for a conservative strategy or in patients at increased risk of bleeding.. Clinicians should be familiar with the updated 2007 ACC/AHA guidelines and the clinical trial evidence that serves as the basis for these recommendations. It is paramount for institutions to outline a preferred and consistent treatment approach. These decisions should involve a review of established efficacy, bleeding risk, need for anticoagulant reversal, costs, and clinician familiarity with different treatment regimens.

Topics: American Heart Association; Angina, Unstable; Anticoagulants; Clopidogrel; Drug-Eluting Stents; Enoxaparin; Fondaparinux; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Polysaccharides; Practice Guidelines as Topic; Recombinant Proteins; Ticlopidine; United States

Fondaparinux is a synthetic pentasaccharide with powerful anticoagulant properties, which may also reduce ischemia-reperfusion (I/R) injury in vivo. However, the relative contributions of the anticoagulant and anti-inflammatory activities of fondaparinux to the observed protection are unknown. To address this issue, a crystalloid-perfused heart model was used to assess potential effects of fondaparinux on IR-induced heart injury in the absence of blood. Fondaparinux protects the ischemic myocardium independently of its haemostasis effects. Fondaparinux improved post ischemic myocardial contractile performance and tissue damage. These beneficial effects of fondaparinux may be related to the observed reduction in IR-induced oxidative stress and endothelial activation. In addition, fondaparinux altered NADPH oxidase activity and phosphorylated extracellular signal-regulated kinase (ERK) 1/2, suggesting activation of survival signaling pathways. The present study provides novel information by demonstrating that fondaparinux can attenuate inflammatory responses and oxidative stress in connection with IR heart injury. These findings could represent a potential therapeutic strategy for the prevention of myocardial dysfunction.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cells, Cultured; Coronary Vessels; Disease Models, Animal; Endothelial Cells; Fondaparinux; Hydrogen Peroxide; Leukocyte Rolling; Male; Microvessels; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Myoblasts, Cardiac; Myocardial Contraction; Myocardial Infarction; Myocardial Reperfusion Injury; NADPH Oxidases; Oxidation-Reduction; Oxidative Stress; Perfusion; Phosphorylation; Polysaccharides; Rats; Rats, Sprague-Dawley; Ventricular Function, Left; Ventricular Pressure

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

Topics: Anticoagulants; Enoxaparin; Fondaparinux; Hemorrhage; Humans; Myocardial Infarction; Polysaccharides

Topics: Angina, Unstable; Anticoagulants; Dose-Response Relationship, Drug; Enoxaparin; Fondaparinux; Hemorrhage; Heparin; Humans; Myocardial Infarction; Polysaccharides

Topics: Anticoagulants; Factor X; Fondaparinux; Humans; Myocardial Infarction; Polysaccharides

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Artery Bypass; Drug Therapy, Combination; Enoxaparin; Fondaparinux; Hemorrhage; Heparin; Humans; Myocardial Infarction; Polysaccharides; Research Design

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Clinical Trials, Phase III as Topic; Drug Therapy, Combination; Electrocardiography; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Heparin; Humans; Intracranial Hemorrhages; Multicenter Studies as Topic; Myocardial Infarction; Polysaccharides; Recurrence; Risk; Treatment Outcome

Topics: Anticoagulants; Factor X; Fondaparinux; Hemorrhage; Humans; Myocardial Infarction; Polysaccharides; Risk

Topics: Anticoagulants; Factor X; Fondaparinux; Hemorrhage; Humans; Myocardial Infarction; Polysaccharides; Risk

Topics: Anticoagulants; Factor X; Fondaparinux; Humans; Myocardial Infarction; Partial Thromboplastin Time; Polysaccharides; Pulmonary Embolism; Risk; Venous Thrombosis

Topics: Acute Disease; Anticoagulants; Antithrombin III; Coronary Disease; Drug Therapy, Combination; Electrocardiography; Fondaparinux; Hemorrhage; Heparin; Humans; Incidence; Myocardial Infarction; Platelet Aggregation Inhibitors; Polysaccharides; Registries; Severity of Illness Index; Syndrome; Thrombocytopenia

Topics: Acetanilides; Angina, Unstable; Anti-Arrhythmia Agents; Calcium Channel Blockers; Coronary Disease; Dose-Response Relationship, Drug; Enzyme Inhibitors; Fibrinolytic Agents; Fondaparinux; Humans; Hydantoins; Imidazoles; Imidazolidines; Multicenter Studies as Topic; Myocardial Infarction; Nicorandil; Piperazines; Polysaccharides; Randomized Controlled Trials as Topic; Ranolazine; Treatment Outcome