1. The efficacy and safety of oral Rivaroxaban in patients with permanent inferior vena cava filter: a pilot case-control study
Lobastov K., Barinov V., Schastlivtsev I., Boyarintsev V.
The Pirogov’s Russian National Research Medical University
Clinical Hospital no.1 of the President’s Administration of Russian Federation
INTRODUCTION
Treatment protocol. Before IVC filter implantation the diagnosis of proximal DVT was confirmed by duplex ultrasound. All patients had initial treatment with LMWH for 48 hours followed by transitioning to longer-term anticoagulation with a vitamin K antagonist. Those patients who refused assigned anticoagulation were allowed to choose a new oral anticoagulant and after obtaining the consent they were treated with Rivaroxaban 15 mg twice daily for the first 3 weeks, followed by 20 mg once daily. The duration of treatment was lifelong.
In all patients included into the study the IVC filter for various reasons had not been removed after implantation and retrievable filters were considered as permanent.
IVC filters were patent in both groups during observation period.
No PE was found in both groups.
Recurrent DVT was found in one patient in control group at 12 month (0% vs 6.6%, n.s.).
Bleeding was found in 2 patients in Rivaroxaban group and in 3 patients in VKA group (13.3% vs 20.0% n.s., Fig.2),
In control group bleedings were more severe: one intracranial hemorrhage and two skin hemorrhage versus one skin and one gingival hemorrhage in Rivaroxaban group.
Time of observation (month) 6 12 18 24
Patients at risk (Rivaroxaban) 15 14 8 2
Patent IVC filter
Recurrent DVT
Major bleeding
Minor bleeding 1
Patients at risk (VKA) 13 11 5
Venous thromboembolism (VTE) that encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE) has remained a significant and not fully addressed medico-social problem for many years worldwide. At present, standard treatment of patients with VTE involves several anticoagulant regimens: prescription of parenteral anticoagulant overlapping with and transitioning to longer-term treatment with a vitamin K antagonist (VKA), long-term administration of low molecular weight heparin (LMWH), the use of novel oral anticoagulants (NOACs: Rivaroxaban, Apixaban, Dabigatran) with or without initial administration of LMWHs. However, in a subset of patients, anticoagulation therapy is contraindicated or ineffective, and these patients require the placement of inferior vena cava (IVC) filter.
Indications for IVC filter placement according to the Russian Clinical Guidelines are as follows:
Rivaroxaban (20 mg q.d.)
VKA (INR )
LMWH
Rivaroxaban (15 mg b.i.d.)
24-48 hours
3-5 days
3 weeks
Omit one dose, 24 hours after consuming of previous dose
INR<2,5
Attempt to remove IVC filter
IVC filter implantation
Enrolling and following up
NOT REMOVED
Confirmed DVT
REMOVED
anticoagulation therapy is contraindicated
proximal DVT with free-floating thrombus (≥ 4 cm, potentially lethal threat of pulmonary embolism)
propagation of DVT at the background of therapeutic anticoagulation
recurrent PE in patients with high pulmonary hypertension
Figure 2. Total bleeding
Cumulative bleeding-free survival rate
VKA (n=15)
Rivaroxaban (n=15)
HR=0.65
(95% CI: )
If indicated, preference is given to retrievable IVC filters which in some cases could not be removed and become permanent. However all patients with retrievable and permanent IVC filters require anticoagulation according to Russian Guidelines. New oral anticoagulants, Rivaroxaban in particularly, could be an alternative option for the DVT patients with IVC filters. Despite the fact that patients with IVC filter were excluded from the studies of NOAC, it is not a contraindication.
Patients follow-up. The maximum follow-up period was 24 months. Patients were evaluated at 6th, 12th, 18th and 24th month after intervention with clinical examination, duplex ultrasound of IVC system and revision of medical records.
Statistical analysis: chi-squared test, Kaplan-Meier statistics, Cox regression (SPSS v.19.0)
OBJECTIVE
RESULTS
The objective of the study is to evaluate the efficacy and safety of Rivaroxaban in comparison with vitamin K antagonist in patients with permanent IVC filter which require lifelong anticoagulant therapy.
The study was started in 2013 and ongoing.
Patient characteristics. Totally 15 patients were treated with Rivaroxaban: 8 men and 7 women, age: years (mean – 65.6±15.2) with 1-6 (2.9±1.4) individual risk factors for venous thromboembolism (Fig.1).
Each patient treated with Rivaroxaban was matched the patient from control group treated with VKA. Matching criteria were as follows: age (±5 years), sex and the number of individual risk factors (±1). Matching was successful in 100%.
In patients enrolled into the study attempts to remove IVC filter were made during 3 weeks after implantation. The main reasons of failure in filter removing were technical inability (76.7%), persistence of irreversible individual risk factors (cancer, lower limbs paralysis – 13.3%), persistence of free-floating thrombus (10%).
Figure 1. The incidence of individual risk factors for VTE
Ultrasound image of patent IVC filter at 24 month after implantation in patient treated with Rivaroxaban
METHODS
Design: pilot prospective observational case-control study.
Clinical center: Clinical Hospital no.1 of the President’s Administration of Russian Federation.
Ethics: The study was approved by the local Institutional review board (IRB).
The inclusion criteria: recurrent proximal DVT with free-floating thrombus (≥ 4 cm), implantation of retrievable IVC filter and failure to remove it during 3 weeks, given informed consent.
The exclusion criteria: suspected PE, severe renal or liver failure, contraindication to anticoagulant therapy.
Primary outcome measures: the patency of IVC filter, the rates of VTE recurrence, major and minor bleedings.
CONCLUSION
A better understanding of NOACs features may help to improve treatment algorithms for patients with non-removable IVC filters in clinical practice. This study seems to suggest that rivaroxaban is associated with similar efficacy and safety and does not lead to the filter obstruction, as compared with standard therapy, but results need to be confirmed in randomized controlled trials.
Authors disclosed:
Lobastov K. received honoraria from BAYER for lectures and travel funding
Barinov V. received honoraria from BAYER for lectures and travel funding
Schastlivtsev I. received honoraria from BAYER for lectures and travel funding
Boyarintsev V. nothing to disclose
General disclosure.
This study was made without any funding. BAYER company supports this publication but has no influence on the design of the study, data collecting and processing, final results and making decision about publication.
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