BRIDGING WITH RIVAROXABAN IN PATIENTS WITH CHRONIC USE OF VITAMIN K ANTAGONISTS
A. Majluf Cruz, M. Moreno-Hernandez, J. Garcia-Chavez, J. Vela-Ojeda, J. Hernandez-Juarez, E. Coria-Ramirez
Unidad de Investigacion Medica en Trombosis, Hemostasia y Aterogenesis, IMSS, Mexico City, Mexico
Results
Purpose
Vitamin K antagonists (VKAs), are indicated to prevent arterial or venous thromboembolism
(VTE) (1). However, there is a high risk of bleeding associated with AVKs in patients
undergoing major surgery or high-bleed-risk procedures. Bridging therapy may be
considered in the periprocedural period (2). Because half-live of rivaroxaban is 7-11h (3), it
could be stopped 24h before a procedure. Its rapid onset of action and predictable effects
may simplify resumption of AVKs, potentially at pre-established times depending upon the
procedural bleeding risks when adequate hemostasis has been achieved. Our aim was to
evaluate the use of rivaroxaban vs. enoxaparin for the bridging therapy in individuals at
high-risk of thrombosis during an elective procedure or surgery
Methods
Patient population. A prospective, comparative study. Drugs were administered at home.
Consecutive patients were enrolled from March 1, 2009 to June 30, 2011. Aims. To
determine the incidence of perioperative thromboembolism and major/minor bleeding
during bridging and in the 30 PO days. Inclusion criteria. Patients >18 year-old, VKA for
prosthetic heart valves (PHV), atrial fibrillation (AF), or VTE; duration of AVK before the
procedure of at least 3 mo. Exclusion criteria. Discontinuation of AVK >1 mo before
enrollment; renal insufficiency, major bleeding within 6 mo, platelets <100,000/uL,
concomitant severe pathologies; pregnancy; BW<40/>100 Kg; life expectancy <2 months;
known allergy to rivaroxaban or enoxaparin; HIT history; enrollment in another bridging
study within 30 days. Specifically for the rivaroxaban group, patients were excluded if they
were unable to take the drug 12 h after surgery. Study design. The perioperative
management of anticoagulation is outlined in Fig. 1. In cases of excessive intraoperative
hemorrhage, the interruption of therapeutic anticoagulant therapy was extended up to 72 h.
The surgeon had the option of delaying the first postoperative rivaroxaban or enoxaparin
doses in the case of increased risk for bleeding.
Baseline characteristics of the study population as well as VKA indications are shown in
Table 1. Two-hundred and ninety-five patients (49.8%) belonged to the rivaroxaban group
and 297 (50.2%) to the enoxaparin group. In total, 381 patients (192 of the rivaroxaban
group) underwent major surgery and 211 (104 in the rivaroxaban group) underwent nonmajor invasive procedures. None patient required preoperative VK administration. A cutoff
INR of <1.2 to allow interventional procedures was achieved in 100% of patients. Table 2
shows the results of the efficacy and safety analysis. There were no significant differences
Table 1. General characteristics of the patients
in the number of adverse events experienced by
Rivaroxaban Enoxaparin
P
enoxaparin- and rivaroxaban-bridged patients.
(n = 295)
(n = 297)
Thrombocytopenia was observed in 6/1 patients
M/F (n)
148 / 147
148 / 149
ns
M:F ratio
01:01
01:01
ns
in the enoxaparin and rivaroxaban groups,
Age (mean, ranges)
59 (22 - 84) 58 (25 - 90)
ns
respectively. Proportion of enoxaparin or
Men 56 (22 - 79) 53 (25 - 87)
ns
Women 59 (23 - 84) 61 (25 - 90)
ns
rivaroxaban-bridged patients started AVK within
Indication for AVK (n)
24h
of
surgery
was
non-significant.
Bridging
was
VTE
138
136
ns
performed on an out-patient basis in all patients.
AF
74
76
ns
PHV
83
85
ns
The length of hospital stay was not significantly
Major surgery n (%)
192 (50.5)
189 (49.5)
different between both groups
Abdominal
53
55
ns
Dental
Orthopedic
Urologic
Intervention cardiology
Gynecologic
Mammary
Cancer
Cardiothoracic
Intervention radiology
Other
Minor surgery n (%)
GI endoscopy
Biopsy
Cutaneous surgery
Urologic endoscopy
GO endoscopy
Arthroscopy
Other
47
19
19
17
18
4
4
0
3
8
104 (48.9)
42
21
12
12
6
4
7
48
15
21
15
16
2
3
2
2
10
107 (51.1)
40
24
13
10
6
6
8
M: male; F: female; ns = non significant; GI: gastrointestinal;
GO: gynecologic /obstetric
ns
ns
ns
ns
ns
ns
ns
<0.05
ns
ns
ns
ns
ns
ns
ns
ns
ns
Table 2. Efficacy and safety of bridging with rivaroxaban
vs. enoxaparin
VTE
R
E
(n=138) (n=136)
AF/PHV
P
R
E
(n=157) (n=161)
Thromboembolic events
Arterial
Venous
0
1
0
1
0
0
0
0
6
0
7
1
6
1
0
8
1
0
1
0
2
0
ns
2
0
3
0
ns
ns
ns
6
1
9
0
ns
ns
ns
ns
7
1
0
10
2
1*
ns
ns
ns
ns
Bleeding before surgery
Minor
Major
Bleeding during surgery
Minor
Major
Bleeding after surgery
Minor
Major
Death
R: rivaroxaban; E: enoxaparin; *: not related to thromboembolic or bleeding
events
Conclusions
Bridging therapy with rivaroxaban is as effective and safe as the widely accepted
enoxaparin-based bridging in patients with VTE, FA or PHV under long-term
anticoagulation with AVK and requiring surgery
Declaration of interest
The authors have not conflic of interest to declare
Bibliography
Figure 1. Study design
P
1 Hyers TM, et al. Antithrombotic therapy for venous thromboembolic disease. Chest 2001;119 (1 Suppl):176S-193S
2 Jaffer AK, et al. When patients on warfarin need surgery. Cleve Clin J Med 2003;70:973-984
3. Mismetti P, Laporte S. Rivaroxaban: clinical pharmacology. Ann Fr Anesth Reanim 2008;27 (Suppl 3):S16-S21