idrabiotaparinux and apixaban

In recent years, the significant limitations associated with the use of vitamin K antagonists (VKA) have encouraged the development of new agents. Based upon the central roles played by the serine proteases thrombin and Factor Xa in the blood coagulation cascade, direct thrombin inhibitors and direct Factor Xa inhibitors have been developed. These agents, which include the direct thrombin inhibitor dabigatran etexilate and the Factor Xa inhibitors rivaroxaban and idrabiotaparinux are free from many of the limitations of VKAs. According to the results of available phase III randomized clinical trials, both dabigatran and rivaroxaban are effective and safe enough to qualify as ideal oral anticoagulants for the initial and long-term treatment of patients with acute venous thromboembolism (VTE). Rivaroxaban does not require an initial parenteral treatment and can be given in once daily administrations after the first three weeks. Both of them have limitations for the treatment of patients with severe renal failure, and require further investigations in cancer patients and in pregnant patients with VTE. Both of them lack an antidote.

Topics: Anticoagulants; Antithrombins; Benzimidazoles; Biotin; Dabigatran; Humans; Oligosaccharides; Pyrazoles; Pyridines; Pyridones; Thiazoles; Venous Thromboembolism; Vitamin K

In the last few years, several phase III clinical trials of new drug treatments for deep vein thrombosis (DVT) have been carried out or are about to finish. These drugs have a predictable and reliable pharmacokinetic and pharmacodynamic response and do not require monitoring and are consequently an attractive alternative for the treatment of a high proportion of patients with DVT. Dabigatran, edoxaban and idrabiotaparinux have been developed as an alternative to warfarin, and apixaban and rivaroxaban as one-drug only treatment for this disease, with a 1- or 3-week intensified phase of initial treatment, respectively. So far, the reported results show non-inferior efficacy and safety to warfarin or to conventional treatment. Therefore, the new anticoagulants will be particularly useful in patients with unstable INRs, warfarin incompatible pharmacologic interactions, and in those without access to regular coagulation monitoring.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Biotin; Clinical Trials, Phase III as Topic; Dabigatran; Drug Administration Schedule; Humans; Morpholines; Oligosaccharides; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thiophenes; Venous Thrombosis

Cancer-associated thrombosis is a major cause of morbidity and mortality. Although anticoagulation remains the mainstay for prevention and treatment of thrombosis, current anticoagulants are problematic in cancer patients. Parenteral anticoagulants, such as heparin or low-molecular heparin, require daily subcutaneous injection, whereas warfarin requires coagulation monitoring and frequent dose adjustments. Idrabiotaparinux, a reversible long-acting pentasaccharide, and new oral anticoagulants, such as dabigatran etexilate, rivaroxaban and apixaban, have been designed to replace warfarin for extended prevention or treatment of VTE. Clinical trials with these agents have yielded promising results, and dabigatran etexilate and rivaroxaban are already licensed in many countries for thromboprophylaxis after elective hip or knee replacement surgery. In the coming years, these drugs are likely to replace warfarin for most indications. This paper addresses their potential role for prevention and treatment of cancer-related thrombosis.

Topics: Anticoagulants; Benzimidazoles; Biotin; Clinical Trials as Topic; Dabigatran; Humans; Morpholines; Neoplasms; Oligosaccharides; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiophenes; Thrombosis

Atrial fibrillation is already the most common clinically significant cardiac arrhythmia and a common cause of stroke. Vitamin K antagonists are very effective for the prevention of cardioembolic stroke but have numerous limitations that limit their uptake in eligible patients with AF and reduce their effectiveness in treated patients. Multiple new anticoagulants are under development as potential replacements for vitamin K antagonists. Most are small synthetic molecules that target factor IIa (e.g., dabigatran etexilate, AZD-0837) or factor Xa (e.g., rivaroxaban, apixaban, betrixaban, DU176b, idrabiotaparinux). These drugs have predictable pharmacokinetics that allow fixed dosing without laboratory monitoring, and are being compared with vitamin K antagonists or aspirin in phase III clinical trials [corrected]. A new vitamin K antagonist (ATI-5923) with improved pharmacological properties compared with warfarin is also being evaluated in a phase III trial. None of the new agents have as yet been approved for clinical use.

Topics: Anticoagulants; Atrial Fibrillation; Benzamides; Benzimidazoles; Biotin; Clinical Trials, Phase III as Topic; Dabigatran; Factor Xa Inhibitors; Humans; Morpholines; Oligosaccharides; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thiophenes; Vitamin K