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Despite the availability of comprehensive evidence-based guidelines there are difficult and controversial areas in the management of venous thromboembolism. Institutions and even countries disagree on the importance of calf vein thrombosis, with some rigorously detecting and treating it and others deliberately not looking for it. The need to treat proximal deep vein thrombosis and pulmonary embolism is accepted but which patients with an unprovoked first event should have long-term anticoagulation has become a difficult clinical decision. We are uncertain how to reduce the incidence of post-thrombotic syndrome seen in a substantial number of patients. How hard to look for an undiagnosed underlying cancer has become a contentious issue particularly in the United Kingdom following the recent publication of a guideline from the National Institute for Health and Clinical Excellence. Whilst we are wrestling with these dilemmas we are entering an era of new anticoagulants and have to solve the logistical problems of introducing them into clinical practice despite cost pressures. These issues will be explored in this review. [ABSTRACT FROM AUTHOR]

Aim To assess the bioequipotency of equimolar doses of idraparinux (2.5 mg) and idrabiotaparinux (3.0 mg). Method In a phase I study, 48 healthy male volunteers were randomized to a single subcutaneous injection of idrabiotaparinux or idraparinux, followed by plasma sampling over 27 days. In a prospective substudy of the phase III EQUINOX trial, 228 patients treated for acute symptomatic deep vein thrombosis received idrabiotaparinux or idraparinux once weekly for 6 months. Plasma sampling was performed within 5 days following the last injection. The primary pharmacodynamic endpoint was the inhibition of activated factor X ( FXa) activity. Maximal anti- FXa activity ( Amax) and area under anti- FXa activity vs. time curve ( AAUC) were calculated. Safety and tolerability were also assessed. Results In both studies, pharmacodynamic anti- FXa vs. time profiles of idrabiotaparinux and idraparinux were superimposable. Ratio estimates (90% confidence intervals [ CIs]) for idrabiotaparinux : idraparinux were 0.96 (0.89, 1.04) for Amax and 0.95 (0.87, 1.04) for AAUC in the phase I study, and 1.11 (1.00, 1.22) for Amax and 1.06 (0.96, 1.16) for AAUC at month 6 in the EQUINOX substudy. Idrabiotaparinux and idraparinux were considered bioequipotent because 90% CIs were within the pre-specified interval (0.80, 1.25). Study treatments were well tolerated. Conclusion Pharmacodynamic parameters reported after single dose in healthy volunteers and after repeated once weekly dosing in patients demonstrated the bioequipotency of idrabiotaparinux and idraparinux based on FXa inhibition. These outcomes support the use of an idrabiotaparinux dose bioequipotent to an idraparinux dose in large clinical trials, and the possibility to substitute idrabiotaparinux to idraparinux for the treatment of venous thromboembolism. [ABSTRACT FROM AUTHOR]

Management of anticoagulation in elderly patients represents a particularly challenging issue. Indeed, this patient population is at high thromboembolic risk, but also at high hemorrhagic risk. Assessment of the benefit-risk balance of anticoagulation is the key point when decisions are made about introducing and/or continuing such treatments in the individual elderly patient. In order to maximise the safety of anticoagulation in the elderly, some specific considerations need to be taken into account, including renal insufficiency, modified pharmacodynamics of anticoagulants, especially vitamin K antagonists, and the presence of multiple comorbidities and concomitant medications. New anticoagulants could greatly simplify and possibly increase the safety of anticoagulation in the elderly in the near future. [ABSTRACT FROM AUTHOR]

Schulman S (McMaster University, Hamilton, ON, Canada; and Karolinska University Hospital, Stockholm, Sweden). New aspects on treatment modalities for thromboembolic episodes (Review). J Intern Med 2010; 268: 109–119. Venous thromboembolism (VTE) has been treated with a glycosaminoglycan, followed by a vitamin K antagonist during the past 60 years. During the past two decades the glycosaminoglycans have undergone refinement, allowing for simplification of care for these patients, but parenteral administration is still required. Therefore, the current completion of phase III trials with selective, predictable and orally available anticoagulants with rapid onset brings promise for a change in paradigm in the treatment of VTE in the next few years. Whereas these efforts will lead to further simplification of the therapy there are also trials conducted to advance the treatment by rapid resolution of the thromboembolism in order to improve long-term outcome. Catheter-directed thrombolysis, perhaps also with thrombus fragmentation and stent insertion, if demonstrated to be successful for the reduction of the postthrombotic syndrome, will only be an alternative for a minority of patients due to the complexity, risks and cost of therapy. This treatment increases the complexity at the same time as new drug regimens offer simplicity. This review focuses on the novel therapies for VTE although the new anticoagulants will also play a major role in the management of arterial disease, which will be briefly presented. [ABSTRACT FROM AUTHOR]