Register und Studien zu den NOAKs sowie klinischer Stellenwert der Antidots

Eine Vielzahl von interventionellen und nicht-interventionellen Studien erlaubt mittlerweile den sicheren Einsatz der Nicht-Vitamin-K-Antagonist-Antikoagulanzien (NOAKs). Sie werden als First-line-Therapie bei venöser Thromboembolie (VTE) und nicht-valvulärem Vorhofflimmern mit erhöhtem Embolierisiko empfohlen. Eine Überlegenheit eines NOAKs gegenüber anderen wurde nicht randomisiert untersucht und so stellen Leitlinien die 4 Substanzen gleichwertig nebeneinander. Umfangreiche Beobachtungen des Gebrauches der NOAKs weltweit bestätigen die Ergebnisse der Zulassungsstudien.

Laufende Studien werden weitere wichtige Einsatzgebiete der NOAKs beleuchten. Im Gegensatz zur orthopädischen Thromboseprophylaxe wird ihr Einsatz bei internistischen Patienten mit erhöhtem Thromboserisiko nicht empfohlen, was nur eine laufende Studie mit Rivaroxaban noch ändern könnte. Zur Prophylaxe und Therapie der VTE bei Patienten mit aktivem Tumorleiden sowie pädiatrischen Patienten laufen große Studienprogramme. Die im Hinblick auf Blutungen riskante Triple-Therapie mit Vitamin-K-Antagonist und dualer Plättchenhemmung wird vermutlich durch besser verträgliche Konzepte abgelöst. Das erste überlegene Konzept liegt mit der Kombination aus Rivaroxaban 15 mg und Clopidogrel 75 mg (oder alternativ Rivaroxaban 2 x 2,5 mg und dualer Plättchenhemmung) nun vor und reduzierte die Blutungsrate um knapp 40 %.

Neben dem bereits zugelassenen Dabigatran-Antidot Idarucizumab lassen die positiven Ergebnisse mit Andexanet eine baldige Zulassung des Antidots für Faktor-Xa-Hemmer erwarten. Insgesamt hat die evidenzbasierte Einführung der NOAKs bereits jetzt den Patienten großen Nutzen gebracht, die eine antithrombotische Therapie benötigen.

A number of interventional and non-interventional clinical trials have enabled the evidence-based use of non-vitamin K antagonists (NOACs) in daily routine. NOACs are the guideline-recommended first-line choice for the treatment of venous thromboembolism and non-valvular atrial fibrillation with increased risk for embolization. None of the four NOACs has been compared to one of the others in a randomized study. Large-scale observations of the routine use of NOACs have confirmed the Phase 3 trial results.

Ongoing studies will examine novel indications. Thromboprophylaxis with NOACs is only recommended in orthopedic patients, not in medical patients, and there is only one ongoing NOAC trial in medical patients investigating rivaroxaban. Patients with cancer as well as pediatric patients will be studied extensively in the next years. The challenging triple therapy with anticoagulant and dual antiplatelet therapy will probably be replaced by novel concepts. The first of possible combinations has been successfully tested: rivaroxaban 15 mg plus clopidogrel (or alternatively rivaroxaban 2 x 2,5 mg plus dual antiplatelet therapy) reduced bleeding rates by approximately 40%.

After the dabigatran antidote idarucizumab has recently been approved, andexanet successfully reversed the effects of rivaroxaban and apixaban. The evidence-based introduction of NOACs has already yielded important benefit for patients requiring antithrombotic therapy.

Key words

Non-vitamin K antagonist oral anticoagulants - clinical studies - real-world data - venous thromboembolism - atrial fibrillation - NOAC antidots

• Literatur

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