Apixaban vs. standard of care after transcatheter aortic valve implantation: the ATLANTIS trial

Abstract

Aims The respective roles of oral anticoagulation or antiplatelet therapy following transcatheter aortic valve implantation (TAVI) remain debated. ATLANTIS is an international, randomized, open-label, superiority trial comparing apixaban to the standard of care. Methods and results After successful TAVI, 1500 patients were randomized (1:1) to receive apixaban 5 mg (2.5 mg if impaired renal function or concomitant antiplatelet therapy) (n = 749) twice daily, or standard of care (n = 751). Randomization was stratified by the need for chronic anticoagulation therapy. Standard-of-care patients received a vitamin K antagonist (VKA) (Stratum 1) or antiplatelet therapy (Stratum 2) if there was an indication for anticoagulation or not, respectively. The primary endpoint was the composite of death, myocardial infarction, stroke or transient ischaemic attack, systemic embolism, intracardiac or bioprosthesis thrombosis, deep vein thrombosis or pulmonary embolism, and life-threatening, disabling, or major bleeding over 1-year follow-up. The primary safety endpoint was major, disabling, or life-threatening bleeding. The primary outcome occurred in 138 (18.4%) and 151 (20.1%) patients receiving apixaban or standard of care, respectively [hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.73–1.16] and there was no evidence of interaction between treatment and stratum (Pinteraction = 0.57). The primary safety endpoint was similar in both groups (HR 1.02; 95% CI 0.72–1.44). In Stratum 1 (n = 451), an exploratory analysis showed no difference for all endpoints between apixaban and VKA. In Stratum 2 (n = 1049), the primary outcome and primary safety endpoint did not differ, but obstructive valve thrombosis was reduced with apixaban vs. antiplatelet therapy (HR 0.19; 95% CI 0.08–0.46), while a signal of higher non-cardiovascular mortality was observed with apixaban. Conclusion After TAVI, apixaban was not superior to the standard of care, irrespective of an indication for oral anticoagulation.

HIF in Gastric Cancer: Regulation and Therapeutic Target

“…Small-molecule drugs mainly refer to organic compounds with molecular weights less than 1000, and they have been widely used and mature in theory [ 113 , 114 , 115 , 116 , 117 ]. Apixaban, widely used in clinical practice, is a small molecule drug whose main mechanism is to inhibit the expression of FXa [ 118 , 119 , 120 , 121 , 122 ]. Researchers have discovered many small-molecule drugs that can inhibit gastric cancer progression by targeting HIF ( Table 8 ).…”

Missing Pieces of the Transcatheter Aortic Valve Replacement Subclinical Leaflet Thrombosis Puzzle

“…The randomized clinical trials of routine anticoagulation with rivaroxaban 10 mg once a day (GALILEO trial [Global Study Comparing a Rivaroxaban-Based Antithrombotic Strategy to an Antiplatelet-Based Strategy After Transcatheter Aortic Valve Replacement to Optimize Clinical Outcomes]) 5 or apixaban 5mg twice a day (ATLANTIS trial [Anti-Thrombotic Strategy After Trans-Aortic Valve Implantation for Aortic Stenosis]) 11 compared with DAPT reported increased risk of death or thromboembolic complications with routine anticoagulation compared with antiplatelet therapy in the absence of an established indication for anticoagulation. Both GALILEO and ATLANTIS noted a significantly lower incidence of valve thrombosis in patients treated with routine anticoagulation after TAVR.…”

Orale Antikoagulation nach Klappeneingriffen – Was ist der Standard?

“…Insbesondere aufgrund der erhöhten nicht kardiovaskulären Mortalität, die sich konsistent auch in der GALILEO-Studie gezeigt hat, ist von oralen Antikoagulation nach TAVI bei Patienten ohne grundsätzliche OAC-Indikation abzuraten [4,11,25].…”

“…In 2 aktuellen randomisierten Studien wurden Vitamin-K-Antagonisten mit den Faktor-Xa-Inhibitoren Edoxaban (ENVISAGE-TAVI) bzw. Apixaban (ATLANTIS, Stratum 1) verglichen [11,12]. In ENVISAGE-TAVI zeigte sich an 1426 Patienten eine Nichtunterlegenheit von Edoxaban im Vergleich zu VKA hinsichtlich eines kombinierten primären Effektivitätsendpunkts (bestehend aus Tod, Myokardinfarkt, ischämischer Schlaganfall, systemischer Thromboembolie, Klappenthrombose und Majorblutungen).…”

“…Dies mag mit zu der höheren Rate an gastrointestinalen Blutungen beigetragen haben, zumindest zeigte eine explorative Analyse der ENVISAGE-TAVI-Studie keinen Unterschied in den Blutungsraten bei Patienten ohne zusätzliche antithrombozytäre Therapie [12]. In der ATLANTIS-Studie (Stratum 1, 977 Patienten mit OAC-Indikation) fand sich nach TAVI mit im Vergleich zu VKA kein Unterschied in ischämischen Endpunkten sowie in der Rate an Blutungen als primärem Sicherheitsendpunkt (zusammengesetzt aus Majorblutung, lebensbedrohlicher Blutung und Disabling-Blutung) [11]. Für die weiteren NOAC (Rivaroxaban, Dabigatran) stehen vergleichbare randomisierte Studien noch aus.…”