fondaparinux and Acute-Coronary-Syndrome

Platelets and the coagulation cascade play key roles in initiation, amplification, and perpetuation of acute coronary syndromes (ACS). In the past few years, there has been great progress in ACS antithrombotic treatment with the introduction of novel anticoagulants (fondaparinux and bivalirudin), more potent P2Y

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Aspirin; Blood Coagulation Factors; Fondaparinux; Hirudins; Humans; Peptide Fragments; Platelet Aggregation Inhibitors; Recombinant Proteins

Enoxaparin and Fondaparinux are potential anticoagulants which are used peri-operatively in the management of patients with Acute Coronary Syndrome (ACS). We aimed to compare the adverse clinical outcomes which are associated with the use of these anticoagulants in patients who were treated for ACS.. Online databases (PubMed/Medline, EMBASE, Cochrane library) were searched for studies which compared differences in clinical outcomes observed with the use of enoxaparin and fondaparinux in patients who were treated peri-operatively for ACS. Statistical analysis was carried out by Revman 5.3 software with odds ratio (OR) and 95% confidence intervals (CI) as the analytical parameters.. Seven studies with a total number of 9618 patients (mainly composed of non-ST elevated myocardial infarction/NSTEMI) were included. This analysis showed mortality to be similarly observed between enoxaparin and fondaparinux with OR: 1.05, 95% CI: 0.67-1.63; P = 0.84. Myocardial infarction (MI) and stroke were also not significantly different throughout different follow up periods. However, minor, major and total bleeding were significantly lower with fondaparinux (OR: 0.40, 95% CI: 0.27-0.58; P = 0.00001), (OR: 0.46, 95% CI: 0.32-0.66; P = 0.0001) and (OR: 0.47, 95% CI: 0.37-0.60; P = 0.00001) respectively during the 10-day follow up period. Even during a follow up period of 30 days or a midterm follow up, major and minor bleeding still significantly favored fondaparinux in comparison to enoxaparin.. In patients who were treated for ACS, fondaparinux might be a better choice when compared to enoxaparin in terms of short to midterm bleeding events. This result was mainly applicable to patients with NSTEMI. However, due to a limited number of patients analyzed, further larger randomized trials should be able to confirm this hypothesis.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Chi-Square Distribution; Enoxaparin; Female; Fondaparinux; Humans; Male; Middle Aged; Non-ST Elevated Myocardial Infarction; Odds Ratio; Patient Selection; Polysaccharides; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Treatment Outcome

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

Topics: Acute Coronary Syndrome; Cardiology; Fondaparinux; Humans; Poland; Polysaccharides; Practice Guidelines as Topic; Societies, Medical

Anticoagulant therapy is a major component in the management of acute coronary syndromes (ACS). Anticoagulant-associated adverse events like heparin-induced thrombocytopenia, bleeding complications and need of close monitoring of anticoagulation led to focus on developing agents causing anticoagulation without affecting primary haemostasis. Fondaparinux, a new-age synthetic anticoagulant, acts by inhibiting factor Xa. It is simple to administer and has low inter and intra-subject variability. Moreover, there is no risk of significant drug interactions and no need for monitoring the platelet count. Efficacy of fondaparinux has been studied in various disorders including prevention of venous thromboembolism in major orthopaedic surgery, abdominal surgery and acutely ill medical patients, treatment of venous thromboembolism, non-ST-elevation acute coronary syndromes and ST-elevation acute myocardial infarction. This article covers the review of fondaparinux and its practical advantages mainly in the management of ACS including non-ST-elevation acute coronary syndromes and ST-elevation acute myocardial infarction.

Topics: Acute Coronary Syndrome; Anticoagulants; Fondaparinux; Humans; Polysaccharides

Antiplatelet and anticoagulant drugs are the mainstay of treatment of acute coronary syndrome (ACS). The last 30 years have seen the development of various agents, a deeper understanding of the pathobiology of this disease, and an evolution in its treatment. We review the role of contemporary agents in ACS and highlight key clinical trials of these agents.

Topics: Acute Coronary Syndrome; Adenosine; Anticoagulants; Aspirin; Benzimidazoles; beta-Alanine; Clopidogrel; Dabigatran; Enoxaparin; Fondaparinux; Heparin; Hirudins; Humans; Morpholines; Peptide Fragments; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Polysaccharides; Prasugrel Hydrochloride; Pyrazoles; Pyridones; Recombinant Proteins; Rivaroxaban; Thiophenes; Ticagrelor; Ticlopidine; Warfarin

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.

Topics: Acute Coronary Syndrome; Adenosine; Adenosine Monophosphate; Anticoagulants; Aspirin; Drug Therapy, Combination; Enoxaparin; Eptifibatide; Fondaparinux; Heparin; Hirudins; Humans; Lactones; Peptide Fragments; Peptides; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Polysaccharides; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Pyridines; Receptors, Thrombin; Recombinant Proteins; Thiophenes; Ticagrelor; Tirofiban; Tyrosine; Warfarin

The efficacy and safety of heparin and low-molecular-weight heparins (LMWHs) are well documented in venous and arterial thromboembolism. Several drawbacks of heparins have inspired the development of newer parenteral anticoagulants for specific indications, including heparin-induced thrombocytopenia (HIT) and percutaneous coronary interventions (PCI). The direct thrombin inhibitors recombinant hirudin and argatroban are now established alternatives for HIT patients, and bivalirudin is one of the most used anticoagulants in PCI. The pentasaccharide fondaparinux is an alternative for LMWH for thromboprophylaxis in various clinical settings and for patients with an acute coronary syndrome (ACS) not scheduled for PCI. In Europe, it was recently approved for treatment of superficial vein thrombosis. Further development of new parenteral anticoagulants is slow and the emphasis has shifted towards development of new oral anticoagulants and antiplatelet drugs. Still, promising new anticoagulants, some targeting less conventional targets in the coagulation system, have been developed and will undergo further clinical evaluation.

Topics: Acute Coronary Syndrome; Antithrombins; Arginine; Fondaparinux; Hirudin Therapy; Hirudins; Humans; Infusions, Parenteral; Peptide Fragments; Percutaneous Coronary Intervention; Pipecolic Acids; Polysaccharides; Randomized Controlled Trials as Topic; Recombinant Proteins; Sulfonamides; Thrombin; Venous Thromboembolism

As acute coronary syndrome (ACS) becomes more common nationwide and current anticoagulation regimens used in patients with ACS continue to possess their shortcomings, the need for new anticoagulants is on the rise. Although heparin and warfarin are used effectively in patients with ACS, they both have significant side effects and delivery issues. New factor Xa inhibitors offer an oral alternative that functions early in the coagulation cascade. The role of these new drugs in ACS is explored here. Electronic search strategies were used to collect reviews, randomized controlled trials, and other studies. Databases used included Medline and Cochrane Library and hand selection. Sources selected were limited to those that discussed factor Xa inhibitors in the context of ACS. Selected studies were then assessed for quality and relevance and those deemed relevant included for analysis. Some of the factor Xa inhibitors such as rivaroxaban offer anticoagulation as effective as, if not more effective, heparin and warfarin with lower risks of bleeding and other adverse effects such as heparin-induced thrombocytopenia. Many of these new agents also come in oral form, making them easy for patients to manage and use daily.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Cyclic N-Oxides; Factor Xa Inhibitors; Fondaparinux; Heparin; Humans; Morpholines; Naphthalenes; Polysaccharides; Propionates; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiophenes; Treatment Outcome; Warfarin

Drugs that inhibit factor Xa have been shown to reduce mortality and morbidity in acute coronary syndromes (ACS). Presently, factor Xa inhibition is most often achieved indirectly with the heparins and, increasingly, fondaparinux. Despite effective anticoagulation with indirect factor Xa inhibition there remains considerable mortality and morbidity in ACS. The recently developed direct factor Xa inhibitors (the xabans) appear to offer promise as alternatives to the heparins. We review the evidence behind indirect and direct factor Xa inhibition in non-ST-segment elevation ACS, ST-segment elevation myocardial infarction, and with percutaneous coronary intervention.

Topics: Acute Coronary Syndrome; Anticoagulants; Blood Coagulation; Factor Xa Inhibitors; Female; Fondaparinux; Heart Conduction System; Heparin; Humans; Male; Polysaccharides; Randomized Controlled Trials as Topic; Venous Thrombosis

Anticoagulation has proven to be a key component in the management of acute coronary syndromes (ACS). Pharmacological agents with various modes of action are utilized to reduce thrombus development by impairing thrombin formation, platelet activation, and platelet aggregation. The optimal management of these patients is to achieve maximal anti-ischemic benefit while avoiding bleeding complications. Synthetic "novel" agents have been developed to specifically target factor Xa or thrombin to achieve this goal. A growing amount of data show that these agents provide a net clinical benefit in the setting of stable ischemic heart disease, unstable angina, non-ST-elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI).

Topics: Acute Coronary Syndrome; Antithrombins; Factor Xa Inhibitors; Fondaparinux; Heparin; Humans; Patient Selection; Polysaccharides

Topics: Acute Coronary Syndrome; Anticoagulants; Antithrombins; Cyclic N-Oxides; Fondaparinux; Hirudins; Humans; Morpholines; Peptide Fragments; Polysaccharides; Pyrazoles; Pyridines; Pyridones; Recombinant Proteins; Rivaroxaban; Thiophenes

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

Recent studies have highlighted the critical importance of bleeding complications on prognosis in patients with acute coronary syndromes (ACS). In fact, the hazard for an adverse cardiovascular event associated with bleeding is similar to that of a myocardial infarction. Several bleeding risk scores are now available that reliably quantify the probability of an ACS patient experiencing a bleeding complication. Consistent and strong correlates of bleeding include older age, female sex, renal impairment, and an invasive management approach. Although patients who tend to bleed are usually more morbid compared with their non-bleeding counterparts, several lines of experimental and clinical evidence suggest an independent and causal pathway for bleeding-associated cardiovascular risk. Given the frequency and adverse prognosis associated with bleeding, interventions that might reduce such complications are now a major emphasis in the current era of ACS treatment. Recent trials have shown that several novel antithrombotics, bivalirudin and fondaparinux, reduce bleeding risk while maintaining efficacy in reducing ischemic events during ACS. Other promising strategies that continue to be tested include the use of vascular closure devices and transradial arterial access during percutaneous coronary intervention.

Topics: Acute Coronary Syndrome; Anticoagulants; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Hirudins; Humans; Incidence; Peptide Fragments; Platelet Aggregation Inhibitors; Polysaccharides; Prognosis; Recombinant Proteins; Risk Assessment; Risk Factors

The prevalence of obesity has increased substantially over recent years. Clinicians are increasingly being challenged with making uncertain anticoagulant dosing decisions, as the optimal dosing strategy for most anticoagulants in the obese patient population remains unknown. Research published to date suggests that the clearance of anticoagulants increases with weight. As obesity is associated with an increased risk of venous thromboembolism and arterial disease, there is an urgent need to establish appropriate anticoagulation regimens for this patient group. Research studies applying the method of pharmacokinetic-pharmacodynamic modelling and simulation could establish an appropriate evidence base and provide direction and reassurance to prescribing clinicians.

Topics: Acute Coronary Syndrome; Anticoagulants; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Double-Blind Method; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Heparin; Humans; Morpholines; Multicenter Studies as Topic; Obesity; Polysaccharides; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Thrombin; Thrombophilia; Venous Thrombosis; Warfarin

Chronic kidney disease (CKD) is prevalent and affects an ever-increasing proportion of patients presenting with acute coronary syndrome (ACS). Patients with CKD have a higher risk of ACS and significantly higher mortality, and are also predisposed to increased bleeding complications. Antiplatelet and antithrombotic drugs form the bedrock of management of patients with ACS. Most randomized trials of these drugs exclude patients with CKD, and current guidelines for management of these patients are largely based on these trials. We aim to review the safety and efficacy of these drugs in patients with CKD presenting with ACS.

Topics: Acute Coronary Syndrome; Adenosine; Aspirin; Chronic Disease; Clinical Trials as Topic; Clopidogrel; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Heparin; Hirudins; Humans; Kidney Diseases; Peptide Fragments; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Polysaccharides; Prasugrel Hydrochloride; Recombinant Proteins; Thiophenes; Ticagrelor; Ticlopidine; Uremia

As an alternative to the inconvenient and labor intensive traditional anticoagulants, Factor Xa inhibitors may offer new options for the prevention and treatment of acute coronary syndromes (ACS) and venous thromboembolism (VTE). Fondaparinux, an indirect FXa inhibitor, has equivalent efficacy but decreased bleeding risk. It has been recommended by the American College of Cardiology (ACC)/American Heart Association (AHA) as the preferred anticoagulant in ACS patients with higher bleeding risk managed with a noninvasive strategy. Based on the composite results of several clinical trials, fondaparinux is also recommended for VTE prevention in the setting of major orthopedic surgery. Rivaroxaban, a direct FXa inhibitor, appears to have at least equal efficacy and safety to established anticoagulants in the prevention of VTE. With advantages such as oral administration and a wide therapeutic window, it may provide a useful alternative to current anticoagulants. Ongoing studies are exploring its use in treatment of VTE and ACS, as well as prevention of stroke among patients with atrial fibrillation. In this review, we examine the key recent studies on efficacy and safety of FXa inhibitors in ACS and VTE management.

Topics: Acute Coronary Syndrome; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Fondaparinux; Humans; Morpholines; Polysaccharides; Rivaroxaban; Thiophenes; Venous Thromboembolism

Fondaparinux (Arixtra) is an anticoagulant that selectively inhibits activated factor X, thereby interrupting the blood coagulation cascade. In OASIS-5, a large pivotal trial in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), subcutaneous fondaparinux 2.5 mg once daily was noninferior to subcutaneous enoxaparin 1 mg/kg twice daily (both agents were administered over a mean of about 5 days in combination with antiplatelet therapy) in reducing death or ischaemic events at 9 days, and the efficacy was maintained for up to 6 months (study end). However, fondaparinux was associated with a significantly lower rate of bleeding than enoxaparin in the first 9 days, and at 3 and 6 months. This lower rate of bleeding led to lower long-term mortality and morbidity with fondaparinux than with enoxaparin. In modelled cost-utility analyses conducted from a healthcare payer perspective in Spain, France and the US with a lifetime horizon, fondaparinux once daily was predicted to be cost effective relative to enoxaparin twice daily with regard to the incremental cost per QALY gained. In Spain and the US, fondaparinux dominated enoxaparin (i.e. was less costly and more effective) and, in the French analysis, the incremental cost per QALY gained with fondaparinux versus enoxaparin was well within recommended thresholds. Results of short-term (6-month) cost analyses in the US and France also favoured fondaparinux over enoxaparin. Sensitivity analyses demonstrated that base-case conclusions were robust over a range of parameter estimates and assumptions, including plausible variations in baseline risk of a cardiac event or baseline risk of bleeding. In conclusion, in patients with NSTE-ACS receiving antiplatelet therapy, fondaparinux was cost effective relative to enoxaparin in cost-utility analyses in Europe and the US. This cost advantage primarily reflects the lower rate of bleeding with fondaparinux than with enoxaparin and the lower rate of mortality and morbidity over the long term.

Topics: Acute Coronary Syndrome; Anticoagulants; Clinical Trials as Topic; Cost of Illness; Cost-Benefit Analysis; Female; Fondaparinux; Health Care Costs; Humans; Male; Polysaccharides

Topics: Acute Coronary Syndrome; Anticoagulants; Fondaparinux; Humans; Polysaccharides

Antithrombotic therapy constitutes the basis of the management of acute coronary syndromes. It combines antiplatelet and anticoagulant therapy. Antiplatelet agents should combine aspirin and agents acting through the ADP pathway such as clopidogrel; newer antiplatelet agents such as prasugrel or ticagrelor have superior anti-ischemic efficacy, compared with clopidogrel. Intravenous glycoprotein IIb/IIIa inhibitors may be used in selected patients at high risk undergoing percutaneous coronary interventions. Unfractionated heparin constitutes the reference anticoagulant treatment. Enoxaparin provides slightly better anti-ischemic efficacy. Newer agents, such as bivalirudin or fondaparinux, reduce bleeding complications, with no improvement in anti-ischemic efficacy. The combination of antiplatelet and anticoagulant agents should be chosen according to the patients' characteristics and the management strategy of the acute coronary syndrome.

Topics: Acute Coronary Syndrome; Adenosine; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Clopidogrel; Disease Management; Drug Synergism; Drug Therapy, Combination; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Polysaccharides; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Recombinant Proteins; Thiophenes; Ticagrelor; Ticlopidine

Acute coronary syndromes still account for high mortality in many countries. Antithrombotic therapy represents a cornerstone in the therapy of acute coronary syndromes. Recent research has focussed on improving anti-ischemic potency and reducing bleeding complications as well as improving predictability of antithrombotic efficacy.. New antithrombotic drugs such as the factor Xa antagonists and the direct thrombin inhibitors have been developed and evaluated in clinical trials. Fondaparinux and bivalirudin are approved for clinical use in acute coronary syndromes. They improve the risk/benefit ratio and make routine control of their antithrombotic effect unnecessary. Other agents are being developed to further improve and facilitate antithrombotic therapy in acute coronary syndromes.. Antithrombotic therapy is essential in acute coronary syndrome. New drugs are being developed to enter clinical practice and improve efficacy and safety of this therapeutic strategy.

Topics: Acute Coronary Syndrome; Anticoagulants; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Hirudins; Humans; Peptide Fragments; Polysaccharides; Recombinant Proteins; Thrombin

The crucial aim in the emergency management of patients presenting with chest pain is the identification of acute coronary syndromes (ACS) and the initiation of appropriate treatment. Institution-specific triage to initial medical or interventional therapies is influenced by the availability of percutaneous coronary intervention (PCI) facilities. Although the use of invasive strategies has increased, most US hospitals do not have PCI facilities. Pharmacological management is an integral part of all treatment strategies, regardless of the availability of interventional capability. Given the growing importance of invasive management strategies, a therapy that is compatible with both medical and invasive therapy options is becoming increasingly important. Aspirin and clopidogrel are recommended for patients with ACS regardless of the conservative or invasive management strategy. With enoxaparin, patients with ACS can seamlessly transition from the medical management phase to the interventional management phase without the need for introducing a second anticoagulant in the cardiac catheterization laboratory. Fondaparinux can be used for patients with ACS treated medically, but should not be used alone during PCI because of the risk of catheter thrombosis. Bivalirudin can be used in non-ST-segment elevation myocardial infarction patients who are managed invasively.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Clopidogrel; Emergency Service, Hospital; Enoxaparin; Fondaparinux; Health Services Accessibility; Hirudins; Humans; Peptide Fragments; Platelet Aggregation Inhibitors; Polysaccharides; Recombinant Proteins; Ticlopidine; Triage; United States

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Emergency Service, Hospital; Evidence-Based Medicine; Fondaparinux; Hirudins; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Polysaccharides; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome

Antithrombotic therapies form the cornerstone of management of acute coronary syndromes (ACS). An ideal antithrombotic agent should reduce ischemic complications while keeping bleeding events to a minimum. Heparins, both unfractionated and low molecular weight, reduce ischemic outcomes but also significantly increase the risk of major and minor bleeding. Moreover, they do not reduce mortality. Therefore, there is a need for newer agents that preserve the benefits of ischemia reduction while decreasing mortality and bleeding risk. Fondaparinux is a synthetic pentasaccharide which specifically targets factor Xa of the coagulation cascade. It has been effectively used in the prevention of and treatment of venous thromboembolic disease. Two large randomized controlled trials of fondaparinux compared to unfractionated and low molecular weight heparins, among patients with ACS have recently been completed. These studies have shown a significantly lower risk of bleeding with fondaparinux compared to heparins, with equivalent or greater reductions in ischemic outcomes. A small but definite increase in the risk of catheter-related thrombosis has been found among patients undergoing coronary interventions, which is ameliorated by the administration of unfractionated heparin. This review outlines the pharmacological properties of fondaparinux and critically examines the available clinical trial data for fondaparinux in ACS.

Topics: Acute Coronary Syndrome; Fibrinolytic Agents; Fondaparinux; Humans; Polysaccharides; Randomized Controlled Trials as Topic

Topics: Acute Coronary Syndrome; Anticoagulants; Congresses as Topic; Factor X; Fibrinolysis; Fondaparinux; Humans; Polysaccharides

Fondaparinux sodium (Arixtra) is a synthetic, sulfated pentasaccharide, selective factor Xa inhibitor that is indicated in Europe for preventing thrombus formation in patients with acute coronary syndromes (ACS; the focus of this review), including those with ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), or unstable angina. The large (n = 20,078), well designed OASIS-5 trial showed that subcutaneous fondaparinux 2.5 mg/day for < or =8 days was noninferior to subcutaneous enoxaparin 1 mg/kg twice daily (once daily in those with renal dysfunction) in reducing death or ischemic events at 9 days and the efficacy was maintained for up to 6 months (study end) in patients with unstable angina or NSTEMI. During this time, major bleeding occurred in fewer fondaparinux than enoxaparin recipients, resulting in a benefit : risk balance favoring fondaparinux. The incidence of death or reinfarction at 30 days was significantly lower in recipients of subcutaneous fondaparinux 2.5 mg/day than in those who received usual care (including unfractionated heparin treatment as indicated) in patients with STEMI in the large (n > 12,000) OASIS-6 trial. There were no differences in the incidence of major bleeding between these groups, resulting in a benefit : risk balance favoring fondaparinux. The specificity and selectivity of fondaparinux, combined with its long half-life and 100% bioavailability, allows once-daily anticoagulation without the need for monitoring activated clotting time. Subcutaneous fondaparinux was noninferior to enoxaparin treatment in patients with unstable angina or NSTEMI, and was more effective than usual care in those with STEMI. Fondaparinux has a favorable tolerability profile, particularly with regard to the risk of major bleeding, and limited data suggest that it is more cost effective than enoxaparin in the short term. Thus, overall, clinical evidence suggests that fondaparinux has a valuable place in the treatment of patients with ACS.

Topics: Acute Coronary Syndrome; Anticoagulants; Clinical Trials as Topic; Fondaparinux; Humans; Polysaccharides; Treatment Outcome

Topics: Acute Coronary Syndrome; Electrocardiography; Factor X; Fondaparinux; Humans; Polysaccharides; Treatment Outcome

Fondaparinux sodium (Arixtra) is a synthetic, sulfated pentasaccharide, selective factor Xa inhibitor that is indicated in Europe for preventing thrombus formation in patients with acute coronary syndromes (ACS; the focus of this review), including those with ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), or unstable angina.The large (n = 20,078), well designed OASIS-5 trial showed that subcutaneous fondaparinux 2.5 mg/day for 12,000) OASIS-6 trial. There were no differences in the incidence of major bleeding between these groups, resulting in a benefit : risk balance favoring fondaparinux. The specificity and selectivity of fondaparinux, combined with its long half-life and 100% bioavailability, allows once-daily anticoagulation without the need for monitoring activated clotting time. Subcutaneous fondaparinux was noninferior to enoxaparin treatment in patients with unstable angina or NSTEMI, and was more effective than usual care in those with STEMI. Fondaparinux has a favorable tolerability profile, particularly with regard to the risk of major bleeding, and limited data suggest that it is more cost effective than enoxaparin in the short term. Thus, overall, clinical evidence suggests that fondaparinux has a valuable place in the treatment of patients with ACS.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Clinical Trials as Topic; Drug Interactions; Fondaparinux; Hemorrhage; Humans; Polysaccharides

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

Fondaparinux is the first selective inhibitor of the coagulation factor Xa which is commercially avaliable for clinical use. It has been approved for the prevention of venous thromboembolism in patients undergoing orthopedic surgery and for the initial therapy of venous thromboembolism. In randomized clinical trials the value of fondaparinux in the treatment of ST-elevation myocardial infarction (STEMI) has been investigated. The PENTALYSE study showed that fondaparinux was at least as effective and safe as unfractionated heparin in 333 patients with STEMI undergoing fibrinolysis with t-PA. In the recent large OASIS-6 trial with 12,092 patients the treatment with 2.5 mg fondaparinux daily significantly reduced death and reinfarctions until day 30 compared with guideline recommended usual care and compared with unfractionated heparin (9.7% vs 11.2%, p = 0.008) without increasing major bleedings (1.0% vs 1.3%, p = 0.13). This advantage was predominantly seen in the subgroups of patients with fibrinolysis and without early reperfusion therapy. However, in the subgroup of primary percutaneous coronary interventions (PCIs) no clinical benefit of fondaparinux was found, but there were more catheter thrombosis and acute thrombotic complications. In summary, fondaparinux is a new antithrombin that is an efficient, safe, and easy to use in treatment for STEMI patients, particularly those not undergoing primary PCI.

Topics: Acute Coronary Syndrome; Anticoagulants; Fondaparinux; Heparin; Humans; Polysaccharides; Randomized Controlled Trials as Topic; Venous Thrombosis

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 acute coronary syndromes (i.e., ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, and unstable angina) share a common pathophysiology: the rupture or breakdown of atheromatous plaque superimposed on intracoronary thrombosis (i.e., atherothrombosis). The aim of this review article was to summarize developments occurring during the last year in antithrombotic therapy for non-ST-segment elevation acute coronary syndromes. Four specific issues are considered: pretreatment with clopidogrel before percutaneous coronary intervention, antiplatelet resistance, indications for glycoprotein IIb/IIIa inhibitors in patients pretreated with clopidogrel, and the role of bivalirudine and fondaparinux in the treatment of these patients.

Topics: Acute Coronary Syndrome; Anticoagulants; Clopidogrel; Fibrinolytic Agents; Fondaparinux; Hirudins; Humans; Peptide Fragments; Polysaccharides; Recombinant Proteins; Ticlopidine

Proper administration of antithrombotic and antiplatelet drugs after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) and renal insufficiency is a challenging task. In this study, we utilized Fondaparinux and Tirofiban (either separately or combined) to treat post-PCI patients with ACS and concurrent renal insufficiency. The patients were followed-up for 1 year. We observed that combined treatment led to a higher number of significant therapeutic effects and better reduced the frequency of bleeding events. Our findings indicate that combined antithrombotic and antiplatelet treatment improves the prognosis in patients with ACS and renal insufficiency who received PCI treatment.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Drug Combinations; Female; Fondaparinux; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Polysaccharides; Postoperative Complications; Renal Insufficiency; Tirofiban; Tyrosine

Microemboli are frequently detected entering the middle cerebral arteries during coronary angiography (CA). Recent studies have reported that cerebral microemboli, especially particulate cerebral microemboli, may cause silent ischemic cerebral lesions.. To investigate whether the occurrence of particulate cerebral microemboli during diagnostic CA is influenced by which guidewire technique is used.. Patients with stable angina pectoris or non-ST elevation acute coronary syndrome, referred for CA, were randomized to initial advancement of catheters with a leading guidewire over the aortic arch or to initial guidewire withdrawal in the descending aorta with advancement of catheters alone. After completed CA (part 1), new catheters and guidewires were advanced with guidewire technique contrary to the one first used (part 2). Patients were continuously monitored with transcranial Doppler (TCD), and cerebral microemboli were automatically counted and differentiated.. Statistical analysis was performed on 41 patients. The results in part 1 were confirmed in part 2. The median number (interquartile range) of particulate cerebral microemboli was significantly higher when catheters were advanced with, compared to without, a guidewire over the aortic arch; overall, 6 (IQR, 1-9) vs 1 (IQR, 0-3); P=.01.. Advancement of catheters with a leading guidewire over the aortic arch with subsequent flushing in the ascending aorta consistently generated more particulate cerebral microemboli, implying that the choice of guidewire technique has an impact on the risk for cerebral lesions during CA.

Topics: Acute Coronary Syndrome; Aged; Angina, Stable; Anticoagulants; Aorta; Aorta, Thoracic; Coronary Angiography; Female; Fondaparinux; Humans; Incidence; Intracranial Embolism; Male; Middle Aged; Polysaccharides; Risk Factors; Treatment Outcome; Ultrasonography, Doppler, Transcranial

We aimed to determine the optimal adjunctive anticoagulation regimen for percutaneous coronary intervention (PCI) in patients presenting with acute coronary syndrome (ACS) initially treated with fondaparinux. The optimal adjunctive anticoagulation regimen for PCI in these patients is unclear. In this open-label, prospective, randomized, multicenter pilot study, we compared treatment with unfractionated heparin (UFH) versus bivalirudin in patients with non-ST-segment elevation ACS initially treated with fondaparinux and undergoing early invasive strategy. The randomized population consisted of 100 patients (62.7 ± 12.7 years, 68% men), all of whom were on clopidogrel. During the angioplasty, patients were randomized to either bivalirudin or UFH therapy in a 1:1 fashion. Baseline clinical and angiographic characteristics were similar except for a higher body mass index in the UFH group (29.4 ± 4.7 vs. 27.3 ± 4.2, P = 0.02). Major bleeding was the primary outcome; a major bleeding event was documented in only 1 patient from the bivalirudin group (2%) and in none from the UFH group (P = 0.49). There was no death, Q-wave MI, or acute revascularization in either group. There was no documentation of stent thrombosis, reinfarction, and catheter thrombus. Data from this prospective, multicenter pilot study suggest that bivalirudin, compared to standard-dose UFH, has a similar safety profile in terms of peri-PCI bleeding and thrombotic events and can be used safely in ACS patients initially treated with upstream fondaparinux who undergo PCI.

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Female; Fondaparinux; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Pilot Projects; Polysaccharides; Prospective Studies; Recombinant Proteins; Treatment Outcome

American College of Cardiology/American Heart Association/European Society of Cardiology (ACC/AHA/ESC) guidelines gave fondaparinux a class I recommendation for use in patients with non-ST elevation acute coronary syndromes (NSTE-ACS) undergoing invasive or conservative strategy. Nadroparin is one of the common anticoagulants used in NSTE-ACS in China. Accordingly, this study compared the safety and efficacy between fondaparinux and nadroparin in patients with NSTE-ACS.. In this prospective, randomized, open-label, and single center study, a total of 300 patients with NSTE-ACS were randomized to receive either fondaparinux (group F, n = 150, 2.5 mg/d) or nadroparin (group N, n = 150, 0.1 ml/10 kg q12 h) for a mean of 4 days. The primary safety endpoint was the incidence of major or minor bleeding at 9 days that was not related to coronary artery bypass grafting (CABG). The primary efficacy endpoints included death, myocardial infarction, or recurrent ischemia at 9 days. All patients underwent a 180-day follow-up.. Baseline characteristics were well matched between the two groups. There was a non-significant 28% relative risk reduction in the primary safety endpoint in group F compared with group N (4.7% vs. 6.7%, HR 0.72, 95%CI 0.42-1.65, P = 0.38). The primary efficacy endpoint was 8.0% in group F and 10.0% in group N (HR, 0.82, 95%CI 0.54-1.71, P = 0.49). The composite of the safety and efficacy endpoints at 9 days (10.0% vs. 16.0%, HR 0.61, 95%CI 0.31-1.10, P = 0.10), 30 days (14.0% vs. 17.9%, HR 0.72, 95%CI 0.47-1.16, P = 0.21), or 180 days (18.7% vs. 27.3%, HR 0.65, 95%CI 0.38-1.11, P = 0.11) showed a non-significant trend toward a lower value in group F.. Fondaparinux resulted in a nonsignificant risk reduction in patients with NSTE-ACS in both bleeding and ischaemic events during short- and long-term follow-up compared with nadroparin.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Female; Fibrinolytic Agents; Fondaparinux; Humans; Male; Middle Aged; Nadroparin; Polysaccharides; Treatment Outcome

In patients with acute coronary syndromes (ACS), the negative impact of baseline haemoglobin levels on ischaemic events, particularly death, is well established, but the association with bleeding risk is less well studied. The aim of this study was to assess the impact of baseline haemoglobin levels on major bleeding complications.. Pooled analysis of OASIS 5 and 6 data involving 32 170 patients with ACS with and without ST-segment elevation was performed. The association between baseline haemoglobin and major bleeding or ischaemic events was examined using multiple regression model.. were 30-day rates of major bleeding, death, and death/myocardial infarction (MI) analysed according to baseline haemoglobin levels. Baseline haemoglobin level independently predicted the risk of overall, procedure-related, and non-procedure-related major bleedings at 30 days [odds ratio (OR) 0.94, 95% CI 0.90-0.98; OR 0.94, 95% CI 0.90-0.99; and OR 0.89, 95% CI 0.83-0.95, respectively, per 1 g/dL haemoglobin increment above 10 g/dL]. In addition, a curvilinear relationship between baseline haemoglobin levels and death at 30 days was observed with a 6% decrease in the risk for every 1 g/dL haemoglobin increment above 10 g/dL up to 15.9 g/dL (OR 0.94, 95% CI 0.90-0.98) and a 19% increase above this value (OR 1.19, 95% CI, 0.98-1.43). A similar relationship for the composite outcome of death/MI was observed.. A low baseline haemoglobin level is an independent predictor of the risk of major bleeding in ACS as well as of the risk of death and death and MI. Among other predictors of bleeding risk, baseline haemoglobin should be taken into account in patients presenting with ACS.. ClinicalTrials.gov number, NCT00139815. http://clinicaltrials.gov/ct2/show/NCT00139815?term=NCT00139815&rank=1.

Topics: Acute Coronary Syndrome; Aged; Analysis of Variance; Angioplasty, Balloon, Coronary; Anticoagulants; Double-Blind Method; Enoxaparin; Female; Fondaparinux; Hemoglobins; Hemorrhage; Heparin; Humans; Male; Middle Aged; Polysaccharides; Treatment Outcome

In the OASIS-5 trial, fondaparinux reduced major bleeding with similar short-term efficacy as enoxaparin but lowered death and stroke during long-term follow-up. The mechanism of lower bleeding and improved efficacy with fondaparinux is uncertain.. We compared the anti-Xa concentration (reflecting drug levels), Xa clot time (reflecting anticoagulant effect) and endogenous thrombin potential (ETP; a global test of hemostatic function) in plasma samples collected 6, 24 and 72 h after the first dose of the study drug in 48 patients randomly assigned fondaparinux 2.5 mg day(-1) and 42 patients assigned enoxaparin 1 mg kg(-1) twice daily in the OASIS-5 trial. Patients assigned to fondaparinux compared with enoxaparin had a significantly lower mean anti-Xa level [0.52 IU mL(-1) (SD 0.22 IU mL(-1)) vs. 1.2 IU mL(-1) (SD 0.45 IU mL(-1)), P<0.0001] and Xa clot time [64.9 s (SD 17.7 s) vs. 111.8 s (SD 29.6 s), P<0.0001], and significantly higher ETP area under the curve (AUC) [386.7 mA (SD 51.5 mA) vs. 206.4 mA (SD 90.6 mA), P<0.001] at 6 h, and these differences remained evident at 24 and 72 h. There was significantly less variability of the results of anti-Xa levels, Xa clot time and ETP AUC for fondaparinux compared with enoxaparin at 6 h (P<0.001 for each comparison).. Fondaparinux 2.5 mg day(-1) compared with enoxaparin 1 mg kg(-1) twice daily produces less variable anticoagulant effect and lower mean anticoagulant intensity. These results most likely explain the reduced risk of bleeding seen with fondaparinux compared with enoxaparin in the OASIS-5 trial and suggest that a lower intensity of anticoagulation than used in the past may be sufficient to prevent recurrent ischemic events and death in patients with ACS who are concurrently treated with aspirin and clopidogrel.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Blood Coagulation; Dose-Response Relationship, Drug; Double-Blind Method; Drug Monitoring; Enoxaparin; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Humans; Injections, Subcutaneous; Middle Aged; Partial Thromboplastin Time; Platelet Aggregation Inhibitors; Polysaccharides; Risk Assessment; Risk Factors; Secondary Prevention; Thrombin; Time Factors; Treatment Outcome

The optimal unfractionated heparin regimen for percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation acute coronary syndromes treated with fondaparinux is uncertain.. To compare the safety of 2 unfractionated heparin regimens during PCI in high-risk patients with non-ST-segment elevation acute coronary syndromes initially treated with fondaparinux.. Double-blind randomized parallel-group trial in 179 hospitals in 18 countries involving 2026 patients undergoing PCI within 72 hours, nested within a cohort of 3235 high-risk patients with non-ST-segment elevation acute coronary syndromes initially treated with fondaparinux enrolled from February 2009 to March 2010.. Patients received intravenously either low-dose unfractionated heparin, 50 U/kg, regardless of use of glycoprotein IIb/IIIa (GpIIb-IIIa) inhibitors or standard-dose unfractionated heparin, 85 U/kg (60 U/kg with GpIIb-IIIa inhibitors), adjusted by blinded activated clotting time (ACT).. Composite of major bleeding, minor bleeding, or major vascular access-site complications up to 48 hours after PCI. Key secondary outcomes include composite of major bleeding at 48 hours with death, myocardial infarction, or target vessel revascularization within day 30.. The primary outcome occurred in 4.7% of those in the low-dose group vs 5.8% in the standard-dose group (odds ratio [OR], 0.80; 95% confidence interval [CI], 0.54-1.19; P = .27). The rates of major bleeding were not different but the rates of minor bleeding were lower with 0.7% in the low-dose group vs 1.7% in the standard-dose group (OR, 0.40; 95% CI, 0.16-0.97; P = .04). For the key secondary outcome, the rates for low-dose group were 5.8% vs 3.9% in the standard-dose group (OR, 1.51; 95% CI, 1.00-2.28; P = .05) and for death, myocardial infarction, or target vessel revascularization it was 4.5% for the low-dose group vs 2.9% for the standard-dose group (OR, 1.58; 95% CI, 0.98-2.53; P = .06). Catheter thrombus rates were very low (0.5% in the low-dose group and 0.1% in the standard-dose group, P = .15).. Low-dose compared with standard-dose unfractionated heparin did not reduce major peri-PCI bleeding and vascular access-site complications.. clinicaltrials.gov Identifier: NCT00790907.

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Catheters, Indwelling; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fondaparinux; Hemorrhage; Heparin; Humans; Male; Middle Aged; Polysaccharides

To compare the efficacy and safety of fondaparinux with that of low molecular weight heparin (LMWH) in the treatment of acute coronary syndrome (ACS).. One hundred and five patients with ACS admitted from November 2009 to August 2010 were randomly divided into two groups. They were all treated with nitrates, β-blockers, angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), statins, clopidogrel, enteric-coated aspirin and other basic drugs. On the basis of the above treatment, the fondaparinux group patients (n=50) received hypodermic injection of fondaparinux 2.5 mg, once a day, and the LMWH group patients (n=55) received hypodermic injection of LMWH 0.4 ml, twice a day, the therapeutic course being 3-8 days in both groups. The therapeutic efficacy, the cardiovascular event and bleeding incidences during 7 days and 30 days of the treatment were observed.. There was no significant difference between the fondaparinux group and LMWH group in the total effective rate (96.0% vs. 92.7%,P>0.05), also no significant differences were found between the two groups in cardiovascular events (death, acute myocardial infarction and recurrence of myocardial infarction) during 7 days and 30 days (7 days : 4.0% vs. 7.3%, 30 days: 8.0% vs. 10.9%, both P>0.05). There was no major bleeding incident, and the incidence of minor bleeding in fondaparinux group was obviously lower than that in LMWH group (2.0% vs. 32.7%, P<0.01).. The efficacy of fondaparinux in the treatment of ACS is not inferior to that of LMWH, and adverse events during and after its administration were significantly lower than those in LMWH group, so that fondaparinux treatment for ACS is safe and can be highly recommended.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Anticoagulants; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Polysaccharides

There is uncertainty regarding the optimal adjunctive unfractionated heparin (UFH) regimen for percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) treated with fondaparinux.. The aim of this study is to evaluate the safety of 2 dose regimens of adjunctive intravenous UFH during PCI in high-risk patients with NSTE-ACS initially treated with fondaparinux and referred for early coronary angiography.. This is an international prospective cohort study of approximately 4,000 high-risk patients presenting to hospital with unstable angina or non-ST-segment elevation myocardial infarction, treated with fondaparinux as initial medical therapy, and referred for early coronary angiography with a view to revascularization. Within this cohort, 2,000 patients undergoing PCI will be eligible for enrollment into a double-blind international randomized parallel-group trial evaluating standard activated clotting time (ACT)-guided doses of intravenous UFH versus a non-ACT-guided weight-adjusted low dose. The standard regimen uses an 85-U/kg bolus of UFH if there is no platelet glycoprotein IIb/IIIa (GpIIb-IIIa) inhibitor or 60 U/kg if GpIIb-IIIa inhibitor use is planned, with additional bolus guided by blinded ACT measurements. The low-dose regimen uses a 50 U/kg UFH bolus, irrespective of planned GpIIb-IIIa use. The primary outcome is the composite of peri-PCI major bleeding, minor bleeding, or major vascular access site complications. The assessment of net clinical benefit is a key secondary outcome: it addresses the composite of peri-PCI major bleeding with death, myocardial infarction, or target vessel revascularization at day 30.. FUTURA/OASIS 8 will help define the optimal UFH regimen as adjunct to PCI in high-risk NSTE-ACS patients treated with fondaparinux.

Topics: Acute Coronary Syndrome; Adult; Anticoagulants; Coronary Angiography; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Electrocardiography; Factor X; Female; Follow-Up Studies; Fondaparinux; Heparin; Humans; Injections, Intravenous; Intraoperative Period; Male; Myocardial Revascularization; Polysaccharides; Prospective Studies; Treatment Outcome; Young Adult

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 OASIS-5 (Organization to Assess Strategies in Ischemic Syndromes-5) trial demonstrated that fondaparinux was noninferior to enoxaparin while reducing the risk of bleeding by 50%. The objectives of our study were to assess the effects of fondaparinux compared to enoxaparin in patients stratified by their Global Registry of Acute Coronary Events (GRACE) score and to examine the ability of the GRACE score to predict bleeding in patients with acute coronary syndromes (ACS).. We analyzed efficacy and safety according to the GRACE admission risk score.. The impact of fondaparinux versus enoxaparin on the primary outcome of death, myocardial infarction, and refractory ischemia at 180 days was similar in the low-, intermediate-, and high-risk groups: 7.0% versus 7.7% (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.75-1.08), 10.2% versus 11.3% (HR 0.89, 95% CI 0.77-1.03), and 20.1% versus 21.1% (HR 0.95, 95% CI 0.85-1.06). Major bleeding rates were higher with increasing GRACE risk scores: 2.2%, 3.2%, and 4.1% in the low, intermediate, and high-risk groups. Six-month mortality was 2.2%, 4.2%, and 12.3% in the 3 groups. The risk of major bleeding was substantially lower with fondaparinux in all groups: 1.6% versus 2.9% (HR 0.55, 95% CI 0.39-0.77), 2.2% versus 4.1% (HR 0.53, 95% CI 0.40-0.70), 2.8% versus 5.5% (HR 0.50, 95% CI 0.38-0.64).. The GRACE score predicted both bleeding and mortality in patients with ACS. The efficacy and safety of fondaparinux were consistent in all risk groups supporting its use in a broad range of ACS patients.

Topics: Acute Coronary Syndrome; Anticoagulants; Enoxaparin; Fondaparinux; Hemorrhage; Humans; Polysaccharides; Prognosis; Risk Assessment; Treatment Outcome

The study aimed to compare the short-term costs and long-term cost-effectiveness of 2 antithrombotics, fondaparinux and enoxaparin, for non-ST-elevation acute coronary syndrome in the United States.. It was based on a large randomized trial of 20,078 patients Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators [OASIS-5] comparing the therapies in these patients. In OASIS-5, fondaparinux patients had about half the rate of major bleeding 9 days after randomization and at least as good clinical outcomes (death, myocardial infarction, major bleeding and stroke) after 6 months of follow-up. Health care resource use and clinical efficacy data from the trial were incorporated into a cost-effectiveness model as applied to a general US health care system both for the time horizon of the study (6 months) and over the longer term.. The 180-day cost analysis indicates that fondaparinux would generate a cost saving of $547 per patient (95% CI $207-$924). Sensitivity analysis suggested that savings could vary between $494 and $733. When 180-day cost and clinical results were extrapolated to long-term cost-effectiveness, fondaparinux was dominant (less costly and more effective in terms of quality-adjusted life-years) under most scenarios.. Fondaparinux is a more cost-effective antithrombotic agent than enoxaparin in non-ST-elevation acute coronary syndrome. This is true across the range of event risks seen in OASIS-5.

Topics: Acute Coronary Syndrome; Anticoagulants; Cost-Benefit Analysis; Electrocardiography; Enoxaparin; Factor X; Follow-Up Studies; Fondaparinux; Guideline Adherence; Health Care Costs; Humans; Polysaccharides; Practice Guidelines as Topic; Time Factors; United States

This study sought to evaluate the relative safety and efficacy of fondaparinux and enoxaparin in patients with acute coronary syndromes (ACS) treated with glycoprotein (GP) IIb/IIIa inhibitors or thienopyridines.. The OASIS 5 (Fifth Organization to Assess Strategies in Ischemic Syndromes) trial showed that fondaparinux reduced major bleeding by 50% compared with enoxaparin while preserving similar efficacy. Whether this benefit is consistent in the presence or absence of concurrent antiplatelet therapy with clopidogrel and GP IIb/IIIa inhibitors is unknown.. Patients with ACS (n = 20,078) were randomized as a part of the OASIS 5 trial to receive either fondaparinux or enoxaparin. The use of GP IIb/IIIa inhibitors or thienopyridines was at the discretion of the treating physician. A Cox proportional hazard model was used to compare outcomes.. Of the 20,078 patients randomized, 3,630 patients received GP IIb/IIIa and 13,531 received thienopyridines. There was a 40% reduction in major bleeding with fondaparinux compared with enoxaparin in those treated with GP IIb/IIIa (5.2% vs. 8.3%, hazard ratio [HR]: 0.61, p < 0.001). A similar reduction was found in those treated with thienopyridines (3.4% vs. 5.4%, HR: 0.62, p < 0.001). Ischemic events were similar between the groups, resulting in a superior net clinical outcome (death, myocardial infarction, refractory ischemia, or major bleeding) favoring fondaparinux (GP IIb/IIIa subgroup 14.8% vs. 18.9%, HR: 0.77, p = 0.001 and thienopyridines subgroup 11.0% vs. 13.2%, HR: 0.82, p < 0.001).. In patients receiving GP IIb/IIIa inhibitors or thienopyridines, fondaparinux reduces major bleeding and improves net clinical outcome compared with enoxaparin.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Drug Therapy, Combination; Enoxaparin; Female; Fondaparinux; Humans; Male; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Polysaccharides; Pyridines; 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

Fondaparinux is thought to have the most favorable risk-benefit profile among all anticoagulants in non-ST-elevation acute coronary syndrome (NSTE-ACS). However, conflicting findings exist whether this holds true in current clinical practice. We aimed to assess the net clinical benefit of fondaparinux versus enoxaparin in the contemporary management of NSTE-ACS.. Analysis of prospective multicenter registry data of NSTE-ACS patients who received fondaparinux or enoxaparin from February 2015, through December 2017. Survival models within a competing risks framework including site-specific random effects, were used to assess the composite of clinically relevant bleedings and major adverse cardiovascular events at 30 days.. Of 2094 patients, 1724 (82%) received enoxaparin and 370 (18%) fondaparinux. Both groups were comparable except for a lower prevalence of diabetes and renal impairment, and greater use of transradial approach in the fondaparinux group. Multivariate analysis revealed a net clinical benefit in favour of fondaparinux versus enoxaparin (Subhazard Ratio [SHR] 0.59; 95%CI 0.37-0.92), mainly driven by a reduction in bleeding (SHR 0.57; 95%CI 0.37-0.89). Exploratory analysis suggested greater reductions in bleeding with fondaparinux among patients undergoing transradial approach, revealing a significant interaction between treatment and vascular access on the multiplicative scale (P. In contemporary management of NSTE-ACS, fondaparinux seems to provide a favorable net clinical benefit compared with enoxaparin, primarily driven by a bleeding reduction. Effect modification on the safety profile of fondaparinux by the vascular access approach warrants further investigation.

Topics: Acute Coronary Syndrome; Anticoagulants; Enoxaparin; Fondaparinux; Humans; Polysaccharides; Prospective Studies; Registries; Treatment Outcome

Topics: Acute Coronary Syndrome; Anticoagulants; Fondaparinux; Heparin; Humans

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

The perioperative bleeding risk in patients receiving fondaparinux versus low-molecular weight heparin before coronary artery bypass grafting has not been reported. We evaluated perioperative coronary artery bypass grafting-related bleeding in patients with acute coronary syndrome preoperatively treated with fondaparinux or low-molecular weight heparin. All patients with acute coronary syndrome from the prospective, European multicenter registry on coronary artery bypass grafting preoperatively treated with fondaparinux or low-molecular weight heparin undergoing isolated primary CABG were eligible. The primary outcome measure was severe or massive bleeding defined according to the Universal Definition of Perioperative Bleeding stratified by P2Y

Topics: Acute Coronary Syndrome; Aged; Blood Loss, Surgical; Cohort Studies; Coronary Artery Bypass; Europe; Factor Xa Inhibitors; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Incidence; Male; Middle Aged; Postoperative Hemorrhage; Propensity Score; Registries

This retrospective chart review was designed to evaluate physician adherence to the prescribing information for fondaparinux regarding adjunctive anticoagulant use during percutaneous coronary intervention (PCI) in patients with an acute coronary syndrome (ACS).. Medical record abstractors at each site obtained information regarding the use of fondaparinux and adjunctive anticoagulants during PCI. Physician adherence to fondaparinux prescribing information regarding the administration of an adjunctive anticoagulant during PCI was estimated using generalized estimating equations. This retrospective study, conducted in 2008-2010, included a total of 1056 patient records from 27 sites across 6 countries (Canada, France, Germany, Greece, Poland, and Sweden). Over 98% of patients had been treated with fondaparinux at the recommended 2.5 mg dose. Use of adjunctive anticoagulant during PCI was 97.5%, giving an adjusted adherence rate of 98.8% (95% confidence interval: 0.97-0.99), with 86.3% of patients receiving unfractionated heparin. Although the sub-group of patients with ST-elevation myocardial infarction who underwent primary PCI was too small to make a definitive conclusion, 70.4% of the 159 patients did not receive fondaparinux immediately prior to (<24 h) or during primary PCI, suggesting that their treating physicians may have been adherent to the prescribing information.. Physician adherence to the prescribing information for adjunctive anticoagulation during PCI in patients with an ACS receiving fondaparinux was high. The results were consistent in each of the six countries and across patient sub-groups.

Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Anticoagulants; Canada; Europe; Factor Xa Inhibitors; Female; Fondaparinux; Guideline Adherence; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Practice Guidelines as Topic; Practice Patterns, Physicians'; Product Surveillance, Postmarketing; Retrospective Studies; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Treatment Outcome

The wide availability of drugs effective in reducing cardiovascular events and the use of myocardial revascularization have greatly improved the prognosis of patients with coronary artery disease. However, the combination of antithrombotic drugs to be administered before the exact knowledge of the coronary anatomy and before the consequent therapeutic strategy can, on one hand, allow to anticipate an optimal treatment but, on the other hand, may expose the patient to a bleeding risk not always necessary. In patients with ST-elevation acute coronary syndrome with an indication to primary angioplasty, the administration of unfractionated heparin and aspirin is considered the pre-procedural standard treatment. The upstream administration of an oral P2Y12 inhibitor, even if not supported by randomized controlled trials, appears reasonable in view of the very high likelihood of treatment with angioplasty. In patients with non-ST elevation acute coronary syndrome, in which it is not always chosen an invasive strategy, the occurrence of bleeding can significantly weigh on prognosis, even more than the theoretical benefit of pretreatment. Fondaparinux is the anticoagulant with the most favorable efficacy/safety profile. Antiplatelet pretreatment must be selective, guided by the ischemic risk conditions, the risk of bleeding and the time schedule for coronary angiography.In patients with stable coronary artery disease, generally treated with aspirin, pretreatment with clopidogrel is advisable in case of already scheduled angioplasty, and it appears reasonable in case of high likelihood, at least in patients at low bleeding risk. In patients candidate to surgical revascularization, aspirin is typically maintained and the oral P2Y12-inhibitor discontinued, with i.v. antiplatelet drug bridging in selected cases.Anti-ischemic drugs are useful in controlling symptoms, but they have no specific indications with regard to revascularization procedures. Statins showed protective effects on periprocedural damage and late clinical events, when administered early. Although randomized data are lacking, it seems reasonable their pre-procedural administration, due to potential advantages without significant adverse effects.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Clopidogrel; Drug Therapy, Combination; Fondaparinux; Heparin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Italy; Myocardial Revascularization; Platelet Aggregation Inhibitors; Polysaccharides; Preoperative Care; Ticlopidine; Treatment Outcome

Recent studies have shown fondaparinux's superiority over enoxaparin in patients with non-ST elevation acute coronary syndrome (ACS), especially in relation to bleeding reduction. The description of this finding in a Brazilian registry has not yet been documented.. To compare fondaparinux versus enoxaparin in in-hospital prognosis of non-ST elevation ACS.. Multicenter retrospective observational study. A total of 2,282 patients were included (335 in the fondaparinux group, and 1,947 in the enoxaparin group) between May 2010 and May 2015. Demographic, medication intake and chosen coronary treatment data were obtained. Primary outcome was mortality from all causes. Secondary outcome was combined events (cardiogenic shock, reinfarction, death, stroke and bleeding). Comparison between the groups were done through Chi-Square test and T test. Multivariate analysis was done through logistic regression, with significance values defined as p < 0.05.. With regards to treatment, we observed the performance of a percutaneous coronary intervention in 40.2% in the fondaparinux group, and in 35.1% in the enoxaparin group (p = 0.13). In the multivariate analysis, we observed significant differences between fondaparinux and enoxaparin groups in relation to combined events (13.8% vs. 22%. OR = 2.93, p = 0.007) and bleeding (2.3% vs. 5.2%, OR = 4.55, p = 0.037), respectively.. Similarly to recently published data in international literature, fondaparinux proved superior to enoxaparin for the Brazilian population, with significant reduction of combined events and bleeding.. Estudos recentes têm apresentado superioridade do fondaparinux em relação à enoxaparina em pacientes com síndrome coronariana aguda (SCA) sem supradesnivelamento de ST, principalmente relacionada à redução de sangramentos. A descrição desse achado em registro brasileiro ainda não foi documentada.. Comparar fondaparinux versus enoxaparina no prognóstico intrahospitalar em SCA sem supradesnivelamento de ST.. Estudo retrospectivo, multicêntrico e observacional. Foram incluídos 2.282 pacientes (335 no grupo fondaparinux e 1.947 no grupo enoxaparina) entre maio de 2.010 e maio de 2.015. Foram obtidos dados demográficos, medicações utilizadas e tratamento coronariano adotado. O desfecho primário foi mortalidade por todas as causas. O desfecho secundário foi eventos combinados (choque cardiogênico, reinfarto, morte, acidente vascular cerebral e sangramentos). A comparação entre os grupos foi realizada por meio de Q-quadrado e teste-T. A análise multivariada foi realizada por regressão logística, sendo considerado significativo p < 0,05.. Em relação ao tratamento, observou-se realização de intervenção coronária percutânea em 40,2% no grupo fondaparinux e 35,1% no grupo enoxaparina (p = 0,13). Na análise multivariada, observaram-se diferenças significativas entre os grupos fondaparinux e enoxaparina em relação a eventos combinados (13,8% vs. 22%, OR = 2,93, p = 0,007) e sangramentos (2,3% vs. 5,2%, OR = 4,55, p = 0,037), respectivamente.. Semelhante aos dados recentemente publicados na literatura mundial, fondaparinux mostrou-se superior à enoxaparina para a população brasileira, com redução significativa de eventos combinados e sangramentos.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Brazil; Enoxaparin; Female; Fondaparinux; Hemorrhage; Hospital Mortality; Humans; Logistic Models; Male; Middle Aged; Polysaccharides; Reproducibility of Results; Retrospective Studies; Risk Factors; Statistics, Nonparametric; Treatment Outcome

Non-ST elevation acute coronary syndrome (NSTE-ACS) imposes a significant health and economic burden on a society. Anticoagulants are recommended as standard therapy by various clinical practice guidelines. Fondaparinux was introduced and evaluated in a number of large randomised, controlled trials. This study therefore aimed to determine the cost-effectiveness of fondaparinux versus enoxaparin in the treatment of NSTE-ACS in Thailand.. A two-part construct model comprising a one-year decision tree and a Markov model was developed to capture short and long-term costs and outcomes from the perspective of provider and society. Effectiveness data were derived from OASIS-5 trial while bleeding rates were derived from the Thai Acute Coronary Syndrome Registry (TACSR). Costs data were based on a Thai database and presented in the year of 2013. Both costs and outcomes were discounted by 3% annually. A series of sensitivity analyses were performed.. The results showed that compared with enoxaparin, fondaparinux was a cost-saving strategy (lower cost with slightly higher effectiveness). Cost of revascularisation with major bleeding had a greater impact on the amount of cost saved both from societal and provider perspectives. With a threshold of 160,000 THB ((4,857.3 USD) per QALY in Thailand, fondaparinux was about 99% more cost-effective compared with enoxaparin.. Fondaparinux should be considered as a cost-effective alternative when compared to enoxaparin for NSTE-ACS based on Thailand's context, especially in the era of limited healthcare resources.

Topics: Acute Coronary Syndrome; Aged; Costs and Cost Analysis; Enoxaparin; Female; Fondaparinux; Humans; Male; Middle Aged; Models, Economic; Polysaccharides; Thailand

Acute coronary syndrome (ACS) refers to a spectrum of life-threatening cardiac diseases usually due to coronary artery plaque rupture, subsequent thrombin generation plaque activation and thrombus formation. To date, no economic analyses have been published about the use of fondaparinux in NSTE-ACS patients in Canada. The purpose of our study is to estimate the lifetime cost-effectiveness of fondaparinux compared to enoxaparin for non-ST-elevation acute coronary syndrome (NSTE-ACS) patients in a Canadian hospital setting.. As an extension of a previous published economic analysis for US patients, an event-based decision analytic model was constructed using clinical and resource use data from OASIS-5, a randomized trial of 20,078 patients from 41 countries. A public payer perspective in the hospital setting was adopted. Resource use data from the trial were valued using Canadian costs. A cost regression model was developed to estimate the mean cost of managing the clinical events over the 180 day period. Annual costs of long-term care for ACS patients were added after 180 days until death. Long-term survival was incorporated using Canadian life tables with further adjustment for additional risks associated with NSTE-ACS. Quality-of-life (utility) decrements from published sources were applied to clinical events. Lifetime costs (2009 CAD$) and quality-adjusted life-years (QALYs), discounted annually at 5 %, were estimated for the typical patient in OASIS-5 (i.e., at mean covariate values).. The trial data showed that fondaparinux is protective against all clinical events observed in the trial. The model showed that: over 180 days, fondaparinux dominates enoxaparin, producing similar estimates of QALYs gained and saving $439; over a patient's lifetime, fondaparinux yields an ICER of $4293/QALY. Based on PSA, the probabilities that fondaparinux dominates enoxaparin (less costly and more effective) and that is cost-effective at a $50,000 threshold were 42 % and 96 %, respectively.. In the Canadian hospital setting, fondaparinux is cost-effective when compared to enoxaparin for the treatment of NSTE-ACS. This result holds both in the immediate post-event period and over the lifetimes of patients.

Topics: Acute Coronary Syndrome; Anticoagulants; Canada; Cost-Benefit Analysis; Decision Support Techniques; Drug Costs; Enoxaparin; Fondaparinux; Hemorrhage; Hospital Costs; Humans; Models, Economic; Polysaccharides; Quality of Life; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Risk Factors; Time Factors; Treatment Outcome

Anticoagulation therapy is routinely used in cases of non ST-segment elevation acute coronary syndromes (NSTE-ACS). The most commonly used drug in such events is enoxaparin, a low molecular weight heparin. Fondaparinux, a synthetic pentasaccharide, is as effective as enoxaparin in terms of survival or residual angina pectoris and significantly reduces bleeding complications. The purpose of this study was to assess the magnitude of cost reductions if enoxaparin were replaced by fondaparinux in Switzerland.. Costs of hospital stay for NSTE-ACS with or without bleeding complications at the Geneva University Hospitals were determined for patients admitted between July 1st, 2007 and June 30th, 2008. These costs were applied to subjects recruited in the AMIS Plus registry, which gathers information on ACS in Swiss hospitals, using three scenarios. Firstly, using the baseline incidence of bleeding episodes observed in the AMIS plus registry. Secondly, using the baseline incidence of haemorrhagic episodes observed in the Geneva University Hospitals sample and thirdly, using the incidence of haemorrhagic episodes observed in the OASIS-5 study. These results and costs were then extrapolated to the national level.. At the Swiss national level, replacement of enoxaparin by fondaparinux would generate annual savings ranging from 854,000 Swiss Francs (scenario 1) to 3,400,000 Swiss Francs (scenario 2) and 2,845,000 Swiss Francs (scenario 3). Estimated savings accounted for 55 to 63% of total hospital costs.. Use of fondaparinux instead of enoxaparin in patients with NSTE-ACS could yield substantial savings at the local as well as the national level in Switzerland.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Costs and Cost Analysis; Drug Costs; Enoxaparin; Factor X; Female; Follow-Up Studies; Fondaparinux; Hospital Costs; Humans; Length of Stay; Male; Polysaccharides; Retrospective Studies; Switzerland; 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 combined use of antithrombotic agents, antiplatelet agents and invasive strategies in acute coronary syndrome without ST-segment elevation (ACSWSTE) reduces cardiovascular events. Fondaparinux has demonstrated equivalence to enoxaparin in reducing cardiovascular events, but with a lower rate of bleeding in patients using fondaparinux.. Evaluate the cost-effectiveness of fondaparinux versus enoxaparin in patients with ACSWSTE in Brazil from the economic perspective of the Brazilian Unified Health System (SUS).. A decision analytic model was constructed to calculate the costs and consequences of the compared treatments. The model parameters were obtained from the OASIS-5 study (N = 20,078 patients with ACSWSTE randomized to fondaparinux or enoxaparin). The target outcome consisted of cardiovascular events (i.e., death, myocardial infarction, refractory ischemia and major bleeding) on days 9, 30 and 180 after ACSWSTE. We evaluated all direct costs of treatment and ACSWSTE-related events. The year of the analysis was 2010 and the costs were described in reais (R$).. On day 9, the cost of treatment per patient was R$ 2,768 for fondaparinux and R$ 2,852 for enoxaparin. Approximately 80% of total costs were associated with invasive treatments. The drug costs accounted for 10% of the total cost. The combined rates of cardiovascular events and major bleeding were 7.3% and 9.0% for fondaparinux and enoxaparin, respectively. Sensitivity analyses confirmed the initial results of the model.. The use of fondaparinux for the treatment of patients with ACSWSTE is superior to that of enoxaparin in terms of prevention of further cardiovascular events at lower cost.

Topics: Acute Coronary Syndrome; Anticoagulants; Brazil; Cost-Benefit Analysis; Enoxaparin; Female; Fondaparinux; Health Care Costs; Humans; Male; Middle Aged; National Health Programs; Polysaccharides; Socioeconomic Factors; Time Factors; Treatment Outcome

Fondaparinux has a favourable efficacy-safety profile but if major bleeding occurs, reversal of antithrombotic treatment is challenging. We present clinical and biological observations from patients treated with rFVIIa for bleeding under fondaparinux.. Fondaparinux-treated patients with bleeding (>10% haematocrit decrease) and cardiovascular collapse were eligible. Patients received a single 90 μg/kg bolus rFVIIa. Clinical success was defined as clinical bleeding control without thrombotic complication. A biological criterion of successful antagonization was defined as a >100% increase in peak thrombin generation (C(max)).. 8 patients were treated (5 ACS, 3 VTE). Patients received aspirin and clopidogrel (n = 5), eptifibatide (n = 2), fluindione (n = 5). In addition to standard haemostatic methods, all patients received rFVIIa and transfusion. Clinical progression was favourable in 4, with bleeding clinically controlled in <6 h. 1 patient died. Biological success was observed in 4 patients with lowest baseline anti-Xa (0.67-0.92 U/L); ¾ had clinical success. In patients with baseline anti-Xa >1.0 U/L (1.14-1.62 U/L), increase in C(max) was low; ¾ had no clinical bleeding control.. This series is the largest describing rFVIIa use to control bleeding in patients under fondaparinux. rVFIIa was considered efficient in 50%, suggesting inefficacy in the context of elevated anti-Xa.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Anticoagulants; Blood Transfusion; Factor VIIa; Female; Fondaparinux; Hemorrhage; Humans; Male; Middle Aged; Polysaccharides; Prospective Studies; Recombinant Proteins; Treatment Outcome; Venous Thromboembolism

Fondaparinux has recently been approved in patients with acute coronary syndromes. The primary aim of this study was to describe the changes in use of anticoagulants between January 2006 and December 2007. The secondary aim was to compare 30-day mortality and rate of a combined end point (30-day death or major bleeding) according to the initial and final anticoagulant agent used.. The rates of use of unfractionated heparin (UFH), enoxaparin, and fondaparinux were compared by periods of 1 month in a multicenter registry. The initial anticoagulant (first used at admission), the final anticoagulant (last used during hospitalization), and switches in anticoagulation were recorded. Temporal trends in monthly use of each anticoagulant were assessed; 30-day mortality rates and the combined end point were compared according to initial and final anticoagulant.. Among 2,874 patients included, the first anticoagulant used was UFH in 26%, enoxaparin in 59%, and fondaparinux in 15%. Respective figures for final anticoagulant were 17%, 56%, and 27%. Although 3 centers did not use fondaparinux (community centers with catheterization laboratory), the overall rate of use of fondaparinux, as initial and final anticoagulant, increased at the expense of the use of enoxaparin. We observed a growing proportion of patients with a switch from UFH to either enoxaparin or fondaparinux, ranging from 5% at the beginning to 25% at the end of the study. Patients treated with UFH were older, had more comorbidities, were at higher risk, and received fewer guidelines-recommended treatments. In patients submitted to angioplasty and treated with fondaparinux, a bolus of 60 IU/kg of UFH was added. After adjustment, 30-day mortality and combined end point rates were higher in patients treated with UFH. Irrespective of the type of acute coronary syndromes, patients treated with enoxaparin or fondaparinux had similar outcomes.. Between 2006 and 2007, the use of fondaparinux in patients with acute coronary syndromes increased considerably, either because it was used instead of enoxaparin or because of a switch from UFH. Adjusted mortality in patients treated with fondaparinux was lower than with UFH and similar to enoxaparin.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Enoxaparin; Female; Fondaparinux; Heparin; Humans; Male; Polysaccharides; Time Factors

Anticoagulant therapy is a major component in the management of acute coronary syndromes (ACS). Four anticoagulant agents are currently commercially available for ACS, namely unfractionated heparin (UFH), enoxaparin, bivalirudin and fondaparinux. We describe the advantages of fondaparinux and the reasons that have hampered its uptake into routine management of ACS. Fondaparinux was shown to be efficacious in the prevention of deep vein thrombosis vs low-molecular-weight heparins, while in the setting of venous thrombo-embolic disease, it was shown to be noninferior to enoxaparin and UFH. Two pivotal studies have demonstrated the efficacy of fondaparinux as an anticoagulant in the setting of ACS, namely OASIS-5 in non-ST elevation ACS, and OASIS-6 in ST elevation myocardial infarction (MI). In OASIS-5, fondaparinux was shown to be noninferior to enoxaparin in terms of death, MI or refractory ischemia at 9 days. Furthermore, a 50% reduction in bleeding complications was obtained with fondaparinux vs enoxaparin, leading to a risk reduction for death. In OASIS-6, fondaparinux was shown to be superior to the comparator (UFH or placebo). European and North American guidelines give fondaparinux a Grade 1A and 1B recommendation respectively, but uptake of fondaparinux in routine practice has been slow. We explore reasons for this, such as prevailing doubts about the efficacy of fondaparinux in the setting of angioplasty, the problem of catheter thrombosis, and the lack of antidote in case of bleeding complications. With the exception of primary angioplasty, fondaparinux is as effective as enoxaparin or UFH, but is also associated with a considerable reduction in bleeding complications, and thus, an undeniable net clinical benefit.

Topics: Acute Coronary Syndrome; Anticoagulants; Catheterization; Enoxaparin; Fondaparinux; Hirudins; Humans; Peptide Fragments; Polysaccharides; Recombinant Proteins; Thrombosis

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

Topics: Acute Coronary Syndrome; Anticoagulants; Enoxaparin; Fondaparinux; Hemorrhage; Humans; Myocardial Ischemia; Polysaccharides; Risk Assessment

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

Fondaparinux is a synthetic pentasaccharide belonging to a new group of anticoagulants that inhibit thrombin formation by inhibiting Factor Xa, which is located at the crossing of both the intrinsic and extrinsic pathways. It has a favorable pharmacokinetic profile, and its effect is predictable and the drug does not need platelet monitoring. Current evidence suggest that fondaparinux is as effective as, if not more than, enoxaparin in the prevention of venous thromboembolism in the postoperative period. It has also been found to have similar effectiveness to enoxaparin and unfractionated heparin in the treatment of venous and pulmonary embolism, respectively. In the field of cardiology, studies have demonstrated that in the setting of acute coronary syndromes, treatment with fondaparinux is not inferior to enoxaparin in preventing major cardiac outcomes, but it is associated with lower risk of bleeding complications, irrespective of the use of percutaneous coronary intervention. During percutaneous coronary intervention, there is a slightly increased risk of catheter thrombosis, which is removed when used along with unfractionated heparin. However, in patients with ST-elevation myocardial infarction, the benefit has been shown in those either receiving thrombolysis or not undergoing any revascularization, but not in subjects undergoing primary percutaneous coronary intervention where unfractionated heparin is still preferred.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Drug Interactions; Enoxaparin; Factor Xa Inhibitors; Fondaparinux; Humans; Polysaccharides; Venous Thromboembolism

Fondaparinux has been shown to reduce the risk of major bleeding and 30-day mortality compared with enoxaparin, in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). However, its cost effectiveness is not well known.. To evaluate the effectiveness and economic attractiveness of fondaparinux relative to enoxaparin in patients with NSTE-ACS treated with triple antiplatelet therapy and early (non-urgent) invasive strategy.. The decision model compares two alternative strategies: subcutaneous (SC) enoxaparin (1 mg/kg 12 hourly) versus SC fondaparinux (2.5 mg/day) in NSTE-ACS patients pre-treated with triple antiplatelet therapy and early revascularization. Cost-effectiveness and cost-utility analyses were performed from a healthcare perspective, based on a Markov model with a time horizon of the patient lifespan. Univariate sensitivity analysis and probabilistic (Monte Carlo) microsimulation analysis were performed.. In the base-case analysis (65 years, Thrombolysis In Myocardial Infarction [TIMI] score 4), the use of fondaparinux was associated with a significant reduction in major bleeding, a slight reduction in adverse cardiac events, and minor improvements in survival and QALYs, together with a small reduction in costs. The dominance of fondaparinux over enoxaparin remained unchanged in the univariate sensitivity analyses. According to Monte Carlo simulation, fondaparinux was cost saving in 99.9% of cases.. Compared with enoxaparin, the use of fondaparinux in patients with NSTE-ACS managed with an early invasive strategy appears to be cost effective, even in patients with a low risk of bleeding.

Topics: Acute Coronary Syndrome; Anticoagulants; Cost-Benefit Analysis; Data Interpretation, Statistical; Decision Support Techniques; Electrocardiography; Fondaparinux; Humans; Markov Chains; Polysaccharides

This chapter about antithrombotic therapy for coronary artery disease is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicans Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggestions are weaker as there is uncertainty regarding the benefits, risks and costs such that individual patients' values may lead to different choices (for a full understanding of the grading see the "Grades of Recommendation for Antithrombotic Agents" chapter by Guyatt et al, CHEST 2008; 133[suppl]:123S-131S). Among the key recommendations are the following: for all patients presenting with non-ST-segment elevation (NSTE) acute coronary syndrome (ACS), without a clear allergy to aspirin, we recommend immediate aspirin (162 to 325 mg po) and then daily oral aspirin (75 to 100 mg) [Grade 1A]. For NSTE ACS patients who are at at least moderate risk for an ischemic event and who will undergo an early invasive management strategy, we recommend "upstream" treatment either with clopidogrel (300 mg po bolus, followed by 75 mg/d) or a small-molecule IV glycoprotein (GP) IIb/IIIa inhibitor (eptifibatide or tirofiban) [Grade 1A]. For NSTE ACS patients who are at least moderate risk for an ischemic event and for whom an early conservative or a delayed invasive strategy of management is to be used, we recommend "upstream" treatment with clopidogrel (300 mg oral bolus, followed by 75 mg/d) [Grade 1A]. For NSTE ACS patients who undergo PCI, we recommend treatment with both clopidogrel and an IV GP IIb/IIIa inhibitor (Grade 1A). We recommend a loading dose of 600 mg of clopidogrel given at least 2 h prior to planned PCI followed by 75 mg/d (Grade 1B). For all patients presenting with NSTE ACS, we recommend anticoagulation with UFH or LMWH or bivalirudin or fondaparinux over no anticoagulation (Grade 1A). For NSTE ACS patients who will undergo an early invasive strategy of management, we recommend UFH (with a GP IIb/IIIa inhibitor) over either LMWH or fondaparinux (Grade 1B). For NSTE ACS patients in whom an early conservative or a delayed invasive strategy of management is to be used, we recommend fondaparinux over enoxaparin (Grade 1A) and LMWH over UFH (Grade 1B). We recommend continuing LMWH during PCI treatment of patients with NSTE ACS when it has been started as the "upstream" anticoagulant (Grade 1B). In low- to moderate

Topics: Acute Coronary Syndrome; Aspirin; Clopidogrel; Electrocardiography; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Platelet Aggregation Inhibitors; Polysaccharides; Risk Assessment; Risk Factors; Ticlopidine; Tirofiban; Tyrosine

Acute coronary syndromes (ACS) are among the most common presentations to emergency departments in North America. An important therapeutic decision facing the clinician is whether antithrombotic therapy is justified and which type confers the lowest risk:benefit ratio. Using low molecular weight heparin (LMWH) has resulted in improved cardiovascular outcomes over unfractionated heparin in the noninvasively treated; however, its use as the antithrombotic agent in the invasive management of ACS has not always been superior. There have also been concerns about bleeding risk with LMWH, especially in the elderly and those with impaired renal function. The longer half-life of LMWH and the complexity of reversing its effect, in the context of multiple antiplatelet and fibrinolytic drugs, have also spurred debate. Finally, there is concern over unwanted thrombotic events with these agents in the cardiac catheterization laboratory.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Fibrinolytic Agents; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Platelet Aggregation Inhibitors; Polysaccharides; Risk Assessment; Risk Factors

Topics: Acute Coronary Syndrome; Bias; Conflict of Interest; Drug Industry; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Humans; Periodicals as Topic; Polysaccharides; Research Support as Topic; United States