Anticoagulant - rivaroxaban
Blood clots are a major cause of morbidity and mortality, whether in the form of deep vein thromboses or as blockages in arteries, where the result can be a stroke or acute heart problems.
Blood clots are a major cause of morbidity and mortality, whether in the form of deep vein thromboses or as blockages in arteries, where the result can be a stroke or acute heart problems.
Venous thromboembolism is also a significant cause of complications in patients undergoing surgery, particularly joint replacements. Prophylactic anticoagulants are commonly administered prior to surgery to reduce the likelihood of thrombotic complications occurring.
The clotting process involves a complex cascade of activating factors in which, ultimately, thrombin converts fibrinogen to fibrin, thus forming a clot. Standard anticoagulant therapies such as the various different forms of heparin work by indirectly inhibiting thrombin. One step earlier in the cascade, Factor Xa activates prothrombin to thrombin, and Bayer has been developing rivaroxaban, a Factor Xa inhibitor designed to reduce coagulation and thus the incidence of clot formation.1
In a multi-centre parallel group double blind double dummy study, a total of 621 patients undergoing total knee replacement were given 2.5, 5, 10, 20 or 30mg rivaroxaban orally twice a day, or 30mg enoxaparin, given subcutaneously twice a day.2 Dosing with rivaroxaban began six to eight hours after surgery and enoxaparin 12 to 24 hours afterwards, and in both cases continued until bilateral venography was carried out five to nine days after the replacement. The primary efficacy endpoint, any incidence of DVT, non-fatal pulmonary embolism or death by any cause, was reached by a quarter of those given the highest dose of the new drug, and 44% of those given enoxaparin. There was no significant difference in the incidence of major post-operative bleeding between any of the patients.
A similar trial was carried out in patients undergoing total hip replacement, with the dose of enoxaparin set at 40mg once a day instead.3 The efficacy endpoint was reached in fewer patients: just 7% of those given the highest dose of rivaroxaban, and 17% for enoxaparin. The incidence of postoperative bleeding was also low, but there was a significant dose trend, with 0.8% of those given the lowest dose of the new blood experiencing a major bleed, rising to 5.4% in the highest dose, compared to 1.5% with enoxaparin.
The drug is currently undergoing Phase III evaluation as a potential prophylactic for venous thromboembolism in surgical procedures. Trials are also planned to look at its potential for preventing strokes in patients with atrial fibrillation, as well as the active treatment of venous thromboembolism.