fondaparinux and Cardiovascular-Diseases

Fondaparinux is a synthetic, five-saccharide chain, AT-dependent, anti-FXa agent. Studies showed that fondaparinux acts in prevention and treatment of venous thromboembolism and in ischemic heart disease, without significant bleeding risk. The drug inhibits thrombin generation, has long half-life and can be administered once-daily without laboratory monitoring. It may be used in HIT treatment.

Topics: Anticoagulants; Cardiovascular Diseases; Factor X; Fondaparinux; Humans; Polysaccharides

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated syndrome associated with heparin exposure, a falling platelet count and a high risk of thrombosis. Cardiovascular patients are at increased risk of HIT due to wide use of heparin in this population. Should HIT be suspected, heparin must be avoided in most situations, and anticoagulation with an alternative anticoagulant should be instituted. Preferred agents include the direct thrombin inhibitors argatroban and lepirudin, whilst bivalirudin or desirudin (other direct thrombin inhibitors) can be used in some situations. The indirect thrombin inhibitors, danaparoid and fondaparinux, can also be considered at times. These agents and their use in cardiac patients, including patients with acute coronary syndrome, percutaneous coronary interventions, acute ST elevation myocardial infarction or cardiac surgery, will be reviewed.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Arginine; Cardiovascular Diseases; Chondroitin Sulfates; Dermatan Sulfate; Drug Administration Schedule; Factor Xa Inhibitors; Fondaparinux; Heparin; Heparitin Sulfate; Hirudins; Humans; Pipecolic Acids; Polysaccharides; Postoperative Complications; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Recombinant Proteins; Sulfonamides; Thrombin; Thrombocytopenia

Topics: Anticoagulants; Arginine; Cardiac Surgical Procedures; Cardiovascular Diseases; Chondroitin Sulfates; Dermatan Sulfate; Diagnosis, Differential; Fondaparinux; Heparin; Heparitin Sulfate; Hirudins; Humans; Peptide Fragments; Pipecolic Acids; Platelet Aggregation Inhibitors; Platelet Factor 4; Polysaccharides; Recombinant Proteins; Sensitivity and Specificity; Sulfonamides; Thrombocytopenia; Thrombosis

Fondaparinux (Arixtra) is the first of a new class of selective indirect antithrombin-dependent factor Xa inhibitors, which inhibits thrombin generation. Fondaparinux is a completely synthetic pentasaccharide. It is a single molecular entity with a well-defined pharmacological target. Fondaparinux has nearly complete bioavailability after subcutaneous injection. The pharmacokinetics of fondaparinux appears predictable and consistent. The peak plasma level is obtained about 2 h after the subcutaneous injection, indicating that a rapid onset of antithrombotic activity is obtained on initiation of treatment. The elimination half-life is about 17 h and it is dose-independent, which allows a convenient once-daily dosing regimen. Fondaparinux is eliminated exclusively by the kidneys. Thus, the estimation of the renal function especially in elderly patients is important for the treatment with fondaparinux, whereas it is contraindicated in patients with severe renal insufficiency. Phase II clinical studies have identified a subcutaneous dose of 2.5 mg once daily for prophylaxis of venous thromboembolism in patients undergoing major orthopaedic surgery. Four phase-III clinical trials using bilateral phlebography for the diagnosis of DVT, demonstrated a combined 50% relative risk reduction of asymptomatic venous thromboembolic events in orthopaedic surgery patients in comparison to the low-molecular-weight heparin (LMWH) enoxaparin. Hemorrhagic complications for fondaparinux were either comparable or higher than those for LMWH but the authors did not judge that the increased bleeding was clinically relevant. A dose ranging study led to the selection of the dose of 7.5 mg at a single daily subcutaneous injection as optimal for the treatment of VTE. In two phase III clinical trials, the dose of 7.5 mg/day is expected to be as efficacious and safe as heparin for the treatment of DVT or PE, respectively. Phase II studies show that the efficacy-to-safety ratio of fondaparinux in the treatment of unstable angina or as an adjunct to thrombolysis in acute myocardial infarction is promising. These results demonstrated that a single anti-Xa agent devoid of antithrombin activity is a potent antithrombotic drug. Fondaparinux has obtained FDA and European health authorities approval. Its use on a large scale will allow the evaluation of its efficacy and tolerance in the daily clinical practice. Chemical modifications of the original synthetic pentasaccharide increase the affini

Topics: Animals; Anticoagulants; Cardiovascular Diseases; Clinical Trials as Topic; Factor Xa Inhibitors; Fondaparinux; Humans; Polysaccharides; Treatment Outcome

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

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