Full Length ArticleRivaroxaban or apixaban in fragile patients with acute venous thromboembolism
Introduction
Subgroup analyses from randomized clinical trials suggested that the use of direct oral anticoagulants (DOACs) may have advantages over standard anticoagulant therapy in fragile patients (those aged ≥75 years, with creatinine clearance levels ≤50 mL/min or weighing ≤50 kg) with venous thromboembolism (VTE) [1,2]. The term fragile has been recently incorporated into the literature, and should not be confused with frail, which usually refers to elderly people with reduced physiologic reserve associated with increased susceptibility to disability. In a prior study using the RIETE registry, fragile patients with VTE had a 2-fold higher rate of major bleeding and half the rate of VTE recurrences during the first 3 months of anticoagulation compared with the non-fragile [3]. In a subsequent study, the use of DOACs in fragile patients with VTE was associated with a significantly lower risk of the composite of VTE recurrences or major bleeding compared with patients receiving standard anticoagulation [4].
The RIETE (Registro Informatizado de Enfermedad Trombo Embólica) registry is an ongoing, multicenter registry of consecutive patients with objectively confirmed VTE with 223 collaborating centers in the Americas, Asia and Europe (ClinicalTrials.gov identifier: NCT02832245). The aim of RIETE has always been to record data including the clinical characteristics, treatment and clinical outcomes in patients with VTE [[5], [6], [7], [8]]. In the current study, we compared the outcomes during anticoagulation in fragile patients with VTE, according to the use of rivaroxaban or apixaban.
Section snippets
Patients and methods
Consecutive patients with acute symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) confirmed by objective testing (compression ultrasonography or contrast venography for DVT; helical CT-scan, ventilation-perfusion lung scintigraphy or angiography for PE) were enrolled in RIETE. Patients were excluded if they were currently participating in a therapeutic clinical trial with a blinded therapy. The rationale, design and methodology of RIETE have been reported elsewhere [9].
Results
From January 2013 to October 2019, 36,889 patients with acute VTE were recruited; of whom 14,831 (40%) were fragile. Overall, 999 fragile patients (15%) received DOACs starting <48 h after VTE diagnosis: rivaroxaban 711 and apixaban 288. Of these patients, 882 were aged ≥75 years, 370 had CrCl levels ≤50 mL/min and 92 weighed ≤50 kg (Table I). Forty-three patients had CrCl levels <30 mL/min. A substantial amount of patients in both subgroups (25% of patients receiving rivaroxaban vs. 40% of
Discussion
In the EINSTEIN-DVT and PE pivotal trials, the risk for major bleeding in fragile patients was significantly lower in those receiving rivaroxaban than in those on standard anticoagulant therapy [11,12]. This difference was not found in non-fragile patients. In the HOKUSAI trial, a higher efficacy was found in fragile patients receiving edoxaban than in those on warfarin [2]. In the AMPLIFY trial, there was no subgroup analysis comparing apixaban vs. standard therapy in fragile patients [13].
Acknowledgements
We express our gratitude to Sanofi Spain for supporting this Registry with an unrestricted educational grant. We also thank the RIETE Registry Coordinating Center, S&H Medical Science Service, for their quality control data, logistic and administrative support.
Authors contributions
Trujillo- Santos J, Moustafa F and Monreal M designed the study, collected data, analyzed the data, discussed the results, performed research and wrote the manuscript. Beroiz P, Alonso A, Morejon E, López-Reyes R, Casado I, Porras JA, Flores K and López-Núñez JJ collected data, discussed the results and revised the final version of the manuscript. The remaining doctors appearing as co-authors in the Appendix collected data, revised and approved the final version of the manuscript.
Source of funding and its roles
RIETE is an investigator-initiated registry. During the first 5 years, it was supported by Red Respira from the Instituto Carlos III, Spain (Red Respira-ISCiii-RTIC-03/11). It has been also supported with nonrestricted educational grants by Sanofi Spain (from 2002 to December 2019) and Bayer Pharma (from 2010 to December 2018) for the rest of the world.
There is no payment per recruited patient. The main incentive for patients and investigators participating in RIETE is to generate new knowledge
Declaration of competing interest
No potential conflicts of interest.
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A full list of RIETE investigators is given in the appendix.