PB0011 - Evaluation of the association between clinical events and apixaban/rivaroxaban’s plasma exposure in patients from the OptimAT study

Sunday, June 25, 2023

18:30 – 19:30 ET

Room: Exhibition

Co-Author(s)

JT

Jean Terrier

Junior consultant and research fellow
Clinical Pharmacology and Toxicology Service, Anesthesiology Pharmacology and Intensive Care Department, Geneva University Hospitals, Geneva, Switzerland
Geneva, Geneve, Switzerland
PG

Pauline Gosselin

Research assistant
Department of Medicine, Division of General Internal Medicine, Geneva University Hospitals, Switzerland
Geneva, Geneve, Switzerland
CC

Christophe Combescure

Biostatistician
Division of Clinical Epidemiology, Geneva University Hospital, Geneva, Switzerland
Geneva, Geneve, Switzerland
Pierre Fontana, MD PhD (he/him/his)

Head of Geneva Platelet Group
Division of Angiology and Haemostasis, University Hospitals of Geneva, Switzerland
Geneva, Geneve, Switzerland
YD

Youssef Daali

Head of the Pharmacological and Toxicological Investigation Unit
Clinical Pharmacology and Toxicology Division, Geneva University Hospitals, Geneva, Switzerland.
Geneva, Geneve, Switzerland

Presenting Author(s)

Jean-Luc Reny, MD, PhD (he/him/his)

Co-head of Geneva Platelet Group
Geneva Platelet Group, Faculty of Medicine, University of Geneva
Geneva, Geneve, Switzerland

Background: There is mounting evidence that direct oral anticoagulants’(DOAC) exposure is linked to clinical events, including bleeding and thrombotic events, which are more frequently seen in patients with extreme DOAC plasma concentrations. However, data from real-life setting are sparse. We present here data on the 2-year clinical follow-up of patients from the OptimAT study (NCT03477331).

Aims: To prospectively study the association between apixaban and rivaroxaban’s plasma concentration with bleeding and thrombotic events.

Methods: The OptimAT study was primarily designed to validate pharmacokinetic modeling of DOAC concentration in hospitalized patient. As part of secondary endpoints, clinical events were monitored over a 2-year follow-up. Clinical event-free survival was analyzed according to apixaban and rivaroxaban’s plasma concentration and categorized as follows: 25-75thpercentiles vs < 25th and>75thpercentiles. Clinical events were defined as a composite outcome including major and clinically relevant minor bleeding according to ISTH definition and thrombotic events including major adverse cardiovascular and thrombo-cardio-embolic events. COX regression analyses were performed to assess the hazard ratios(HR) associated with extreme percentiles of DOACs’ exposure and clinical events.

Results: Clinical and demographic characteristics of the population(n=200) are described in table 1. Major bleeding and thrombotic events were low and comparable to what is reported in landmark trials. No significant association between extreme percentiles of DOACs’ plasma concentrations and clinical events was observed (Figure 1). With respect to the sample size, it was anticipated that the study had 80% power to detect a significant HR of 4.4 or greater.

Conclusion(s): Monitoring of clinical events within the frame of a pharmacokinetic study on antithrombotics provides useful descriptive data on the incidence of these events that is comparable to that previously observed. It also showed a high rate of DOACs modifications in real-life which, combined with the sample size of such studies, hampers the power to detect a relevant risk associated with extreme drug exposure.