Apixaban

 

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Summary

Apixaban is a potent reversible inhibitor of the activated human coagulation factor X. This new oral anticoagulant has favourable pharmacokinetic and pharmocodynamic properties which include a concentration-dependent anticoagulant effect, good oral bioavailability, balanced elimination and excretion, infrequent drug or food interactions, and the lack of liver toxicity. Apixaban has already completed a large part of its phase 3 clinical trial programme. In the ARISTOTLE study, which focused on stroke prevention in atrial fibrillation, apixaban showed a balanced efficacy and safety profile, being superior to warfarin both in the prevention of strokes and in the risk of causing major bleeding. A further trial related to this indication, AVERROES, demonstrated the clear superiority of apixaban compared to aspirin treatment. In the primary prophylaxis of venous thromboembolism after orthopaedic surgery, apixaban successfully completed the ADVANCE study programme and was approved in Europe for patients undergoing elective hip or knee replacement. The results of the AMPLIFY and AMPLIFY- EXT studies will soon show whether the inhibitor is also effective in the treatment and secondary prophylaxis after acute deep vein thrombosis and pulmonary embolism. On the other hand, the use of apixaban in the primary prophylaxis of venous thrombosis in hospitalised medical patients, and its administration on top of antiplatelet therapy to patients who have suffered an acute coronary syndrome, have not received support by the results of ADOPT and APPRAISE-II, respectively. In conclusion, on the basis of the available evidence, apixaban appears to be a valuable therapeutic option for the prevention of venous thrombosis and embolic stroke.

Zusammenfassung

Apixaban ist ein hoch potenter, reversibler Inhibitor des humanen Gerinnungsfaktors Xa (FXa). Es verfügt über günstige pharmakokinetische und pharmakodynamische Eigenschaften einschließlich einer konzentrationsabhängigen Antikoagulationswirkung, einer guten oralen Bioverfügbarkeit, einer ausgewogenen Elimination, eines niedrigen Potenzials von Interaktionen mit anderen Medikamenten und Nahrung und eines günstigen Sicherheitsprofils ohne Lebertoxizität. Apixaban hat bereits einen Großteil seines Phase-III-Studienprogramms abgeschlossen. In der Schlaganfallprophylaxe bei Vorhofflimmern wies Apixaban in der ARISTOTLE-Studie ein sehr ausgewogenes Wirksamkeits- und Sicherheitsprofil auf und senkte signifikant – verglichen mit Warfarin – die Inzidenz rezidivierender (insbesondere hämorrhagischer) Schlaganfälle und peripherer Embolien bei gleichzeitiger Reduktion signifikanter Blutungen. In dieser Indikation bestätigte auch der Vergleich von Apixaban mit Azetylsalizylsäure in der AVERROES- Studie die klare Überlegenheit des Faktor- Xa-Inhibitors. Apixaban absolvierte ebenfalls erfolgreich das ADVANCE-Studienprogramm in der Primärprophylaxe venöser Thromboembolien nach elektivem Hüft- oder Kniegelenkersatz und hat bereits in Europa die Zulassung für diese Indikationen erhalten. Erwartet werden in den kommenden Monaten die Ergebnisse der AMPLIFY- und AMPLIFY- EXT-Studie zur Therapie und Sekundär - prävention der venösen Thromboembolie. Der Einsatz von Apixaban nach einem akuten Koronarsyndrom oder zur Prophylaxe venöser Thromboembolien bei akut erkrankten internistischen Patienten erhielt dagegen von der APPRAISE-II- und ADOPT-Studie keine Unterstützung. Auf der Basis der aktuellen Daten - lage verspricht Apixaban eine wertvolle Option für die Prophylaxe von Schlaganfällen und Venen thrombosen zu werden.

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