fondaparinux and Stroke

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

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

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

Antithrombotic medication can be performed by means of heparins (non-fractionated heparin, low molecular heparins) or the pentasaccharide Fondaparinux as well as with oral vitamin K antagonists. The use of a low molecular heparin is initially recommended for the sake of practicability and safety in case of patients suffering from deep venous thrombosis of the leg and pelvis with subsequent long-term oral medication using a vitamin K antagonist (Marcumar) for anticoagulation. The most frequent indications for long-term anticoagulation are deep leg and pelvis thromboses, pulmonary embolism with atrial fibrillation, artificial prosthetic valves and open oval foramen with ischaemic cerebral infarction. In case of patients with chronic atrial fibrillation it is expedient to initiate permanent anticoagulation according to a risk score. For the purpose of controlling oral anticoagulation it is recommended to employ the INR value in place of Quick's value because these data are better comparable. In case of atherothrombotic diseases secondary prevention will always indicate administration of a thrombocyte aggregation inhibitor. In such cases acetylsalicylic acid is recommended as the standard preparation.

Topics: Administration, Oral; Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atherosclerosis; Atrial Fibrillation; Blood Coagulation Tests; Cerebral Infarction; Drug Therapy, Combination; Female; Fibrinolytic Agents; Fondaparinux; Heart Valve Prosthesis; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Phenprocoumon; Platelet Aggregation Inhibitors; Polysaccharides; Preoperative Care; Prevalence; Primary Prevention; Pulmonary Embolism; Risk Factors; Sex Factors; Stroke; Time Factors; Venous Thrombosis

Several antithrombotic agents in development have the potential to greatly simplify the management of patients with AF or at risk for DVT/PE. Ximelagatran has already completed several phase 3 clinical studies in both of these high-risk, high-cost clinical settings and is poised to become the first practical alternative to warfarin. Although the exact therapeutic roles of ximelagatran and other novel antithrombotics further back in the pipeline remain to be determined, the impact of these nonwarfarin alternatives on the current labor-intensive system of anticoagulation clinics seems certain. Most important, the introduction of safer and equally effective oral anticoagulants that do not require monitoring may increase the percentage of high-risk patients who actually receive preventive therapy. If the institutional energy and resources previously spent on anticoagulation clinics, thrombotic disease management, and quality benchmarking can now be redirected to the delivery of the new generation of easier-to-administer and safer antithrombotic agents, the potential to increase rates of preventive therapy initiation and adherence in managed care populations may be within reach. Given the proven clinical value of anticoagulation, this potential increase in the rate of prophylaxis suggests the possibility that, even in the face of a rapidly aging US population, we are nonetheless entering into a period of reduced morbidity, mortality, and costs from stroke and DVT/PE.

Topics: Atrial Fibrillation; Azetidines; Benzimidazoles; Benzylamines; Clopidogrel; Fibrinolytic Agents; Fondaparinux; Humans; Oligosaccharides; Platelet Aggregation Inhibitors; Polysaccharides; Prodrugs; Pyridines; Stroke; Ticlopidine

Factor X plays a central role in coagulation, being the point of convergence of the extrinsic and intrinsic pathways of blood clotting. It may also act as one of the links between the coagulation and inflammatory pathways. These findings suggest that factor X may represent an attractive target for a new antithrombotic drug. Indeed, a factor X inhibitor, fondaparinux, has already been approved for clinical use to prevent post-operative deep vein thrombosis. Factor X inhibitors are also being evaluated for use in the treatment of the acute coronary syndromes, pulmonary embolism and deep vein thrombosis. Oral factor X inhibitors are also being developed, which may be of use in the outpatient prevention and/or treatment of stroke and thromboembolism.

Topics: Anticoagulants; Clinical Trials as Topic; Factor X; Factor Xa Inhibitors; Fondaparinux; Humans; Polysaccharides; Postoperative Complications; Stroke; Thromboembolism; Venous Thrombosis

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

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

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

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

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

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

Topics: Aged; Cross Reactions; Fondaparinux; Heparin; Humans; Male; Platelet Factor 4; Stroke; Thrombocytopenia

Topics: Factor Xa Inhibitors; Female; Fondaparinux; Humans; Magnetic Resonance Imaging; Middle Aged; Polysaccharides; Stroke; Thrombolytic Therapy

Unfractionated heparin (UFH), low molecular weight heparin or fondaparinux are recommended for venous thromboembolism (VTE) prophylaxis in acutely ill medical patients. There are limited data on the safety of fondaparinux for VTE prophylaxis in ischemic stroke. We examined adverse event frequency in hospitalized patients with ischemic stroke who received VTE prophylaxis with fondaparinux versus UFH.. We performed a propensity score matched analysis on a retrospective cohort of 644 consecutive patients with acute ischemic stroke receiving fondaparinux (n=322) or UFH (n=322) for VTE prophylaxis. Patients who received intravenous tPA and continuous intravenous infusions of UFH were excluded. The primary outcome was major hemorrhage (intracranial or extracranial) and the secondary outcome was total hemorrhage (major and minor hemorrhage) during hospitalization. We also examined the rate of symptomatic VTE.. Mean age of the matched cohort was 71.3±14.1 years, median NIHSS score was 4 (IQR 1-11), median duration of anticoagulant exposure was 5 (IQR 3-8) days, and 98.1% received antiplatelet medications. In the matched cohort, there were less observed major hemorrhages in the fondaparinux group 1.2% (4/322) compared to UFH 3.7% (12/322), but this difference was not significant (OR=0.33, 95% CI 0.08-1.10, p=0.08). There were also no significant differences in total hemorrhage (p=0.15), intracranial hemorrhage (p=0.48), major extracranial hemorrhage (p=0.18) and symptomatic VTE (p=1.00) between the groups.. Fondaparinux is not associated with increased hemorrhagic complications compared with UFH in patients with ischemic stroke. There were low rates of symptomatic VTE in both groups.

Topics: Aged; Anticoagulants; Cohort Studies; Female; Fondaparinux; Heparin; Humans; Male; Polysaccharides; Retrospective Studies; Stroke; Venous Thromboembolism

Topics: Aged; Anticoagulants; Fondaparinux; Humans; Leg; Male; Polysaccharides; Stroke; Stroke Rehabilitation; Venous Thrombosis; Warfarin

Topics: Aged; Antibodies; Anticoagulants; Arthroplasty, Replacement, Knee; Fondaparinux; Heparin; Humans; Infarction, Middle Cerebral Artery; Male; Platelet Factor 4; Polysaccharides; Stroke; Thrombocytopenia; Thrombosis

Topics: Acute Disease; Aged; Anticoagulants; Coagulants; Factor VIIa; Fondaparinux; Hematoma, Subdural, Acute; Humans; Male; Polysaccharides; Recombinant Proteins; Stroke

Heparin and Vitamin K antagonists have been the only available anticoagulants for several decades. Their use has lead to significant achievements in all fields of medicine despite various shortcomings and bleeding complications. With the objective of an improved benefit-/risk ratio selective inhibitors of factor Xa (Fondaparinux) and factor IIa (Ximelagatran) have been developed. Ximelagatran can also be orally administered. The results obtained from various clinical trials with these compounds are extremely encouraging. Thus, a significant improvement of antithrombotic treatment may be expected by their future use in the clinical and out-patient setting.

Topics: Administration, Oral; Anticoagulants; Azetidines; Benzylamines; Biological Availability; Clinical Trials as Topic; Clinical Trials, Phase III as Topic; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Glycine; Humans; Meta-Analysis as Topic; Polysaccharides; Prodrugs; Risk Factors; Stroke; Thrombosis