PB0951 - Are Efficacy and Safety of Direct Oral Anticoagulants modified by Fragility characteristics in Patients with Cancer Associated Thrombosis (CAT)? A Meta-analysis of Randomized Controlled Trials

Monday, June 26, 2023

18:30 – 19:30 ET

Room: Exhibition

Co-Author(s)

sl

silvy laporte

Head of the Clinical Pharmacology Unit
University Jean Monnet
saint-etienne, Rhone-Alpes, France
Cc

Céline chapelle

Msc
Clinical Pharmacology Unit
Saint-Etienne, Rhone-Alpes, France
AM

Andrea Marshall

Statistician
Warwick Clinical Trials Unit
Warwick, England, United Kingdom
vM

valentine Mismetti

Interne
Dept. of Pulmonology and Thoracic Oncology, University Hospital of Saint-Etienne, France
Saint-Etienne, Rhone-Alpes, France

Presenting Author(s)

Géraldine Poenou, MD

Dept of Vascular Medicine and Therapeutics, University Hospital of Saint-Etienne, INSERM U-1059, France
Saint-Etienne, Rhone-Alpes, France

Co-Author(s)

OH

Olivier Hanon

Head of the Service
Geriatrics Department, Hospital Broca, Paris Descartes University, EA4468, Paris, France. Université de Paris, France
Paris, Ile-de-France, France
Olivier Sanchez, MD, PhD

Head of department
Université Paris Cité, Service de Pneumologie et Soins Intensifs, HEGP
Paris, France
Isabelle MAHE, MD, PhD (she/her/hers)

MD,PhD
Paris Cité University, APHP, Hôpital Louis Mourier, Colombes, Internal Medicine Department, INSERM UMR_S1140, and F-CRIN InnoVTE, France
Colombes, Ile-de-France, France
AY

Annie Young, PhD

Head of the Service
Warwick Clinical Trials Unit, University of Warwick, Coventry, UK
Warwick, England, United Kingdom

Background: Numerous meta-analyses comparing direct oral anticoagulants (DOAs) with LMWHs in patients with Cancer Associated Thrombosis (CAT) have been published, but none of them evaluated whether patients' fragility characteristics could impact the efficacy and safety outcomes.

Aims: To assess the impact of patient fragilities on treatment effect in patients with CAT using data from randomized clinical trials with a blind evaluation (CRD42021266227).

Methods: The efficacy and safety endpoints were the cumulative incidence of recurrent venous thromboembolism (rVTE) and major bleeding (MB) at the end of the treatment period. All endpoints were assessed according to 3 fragility characteristics: advanced age (75 years or over), renal insufficiency (CrCL less than 50 ml/min), low body weight (60 kg or less). Treatment effect was estimated using hazard ratios (HR) and 95% confidence intervals (CI). As treatment effect estimates of different subgroups are not independent, we meta-analyzed the impact of fragility characteristics calculated in each study by the ratio of HR (RHR) estimated in patients with fragility characteristics relative to those estimated in patients without.

Results: Four studies were eligible. Regarding rVTE, advanced age, renal insufficiency, and small body weight do not seem to impact the treatment effect, with respective RHR close to 1. Regarding MB, advanced age is a possible modifier of treatment effect, with an estimated RHR equal to 2.51 (95% CI 0.87;7.29) (meaning a non-significant reduction of the treatment effect of 151% in elderly patients compared to younger patients) (Figure).

Conclusion(s): This meta-analysis suggests that treatment effect on MB could be affected by advanced age in CAT patients. No other modifiers were identified, the presence of cancer being probably the most important fragility criteria. Before additional data to confirm this result, there is no reason to date to restrict the indications of DOAs in patients with CAT and fragility characteristics by respecting those of the randomized trials.