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Aspirin as Effective as Rivaroxaban for Preventing
VTE After Total Hip or Knee Arthroplasty
Standard aspirin is as effective as the newer,
direct oral anticoagulant (DOAC) rivaroxa-
ban for preventing venous thromboembolism
(VTE) in patients who have undergone total
hip arthroplasty (THA) or total knee arthro-
plasty (TKA), according to a report published
in The New England Journal of Medicine.
“DOACs are commonly prescribed for
extended prophylaxis [as recommended in
evidence-based guidelines] because of their
effectiveness, safety, and convenience of use,”
explained David R. Anderson, MD, of the
Division of Hematology at the Dalhousie
University in Nova Scotia, and co-authors.
However, “aspirin, because of its efficacy, low
cost, and well-established side-effect profile,
[is] potentially a good choice for extended
prophylaxis.”
In the EPCAT II (Extended Venous
Thromboembolism Prophylaxis Comparing
Rivaroxaban to Aspirin Following Total Hip
and Knee Arthroplasty II) trial, investigators
compared the safety and efficacy of rivar-
oxaban and aspirin after an initial five-day
postoperative course of the DOAC.
The double-blind, randomized, controlled
trial enrolled 3,427 patients between January 2013
and April 2016 from 15 university-affiliated
health centers in Canada. All patients were un-
dergoing elective unilateral primary or revision
THA or TKA. Patients were excluded if they had
hip or lower limb fracture during the previous
three months or metastatic cancer. Patients
with long-term aspirin use at a dose of less than
100 mg per day could participate.
The mean patient age was 62.8 years. Most
patients (91.9%) underwent primary arthro-
plasty procedures, and the average hospital stay
was 3.5 days. All patients received in-hospital
prophylaxis with oral rivaroxaban 10 mg once-
daily for five days after surgery.
Those undergoing TKA (n=1,620) were
randomized to receive an additional nine days
of thromboprophylaxis with either rivaroxaban
10 mg (n=815) or aspirin 81 mg (n=805); those
undergoing THA (n=1,804) were randomized
to receive an additional 30 days of rivaroxaban
10 mg (n=902) or aspirin 81 mg (n=902).
At randomization, 855 people were receiv-
ing long-term aspirin prophylaxis: 372 (20.6%)
in the THA cohort and 483 (29.8%) in the TKA
group.
Three patients withdrew consent, so 3,424
people were included in the primary analysis:
1,717 in the rivaroxaban group and 1,707 in the
aspirin group.
During the 90-day follow-up, symptomatic
VTE (defined as deep vein thrombosis [DVT]
or pulmonary embolism [PE]; primary efficacy
endpoint) occurred at similar rates in the aspirin-
and rivaroxaban-treated patients (0.64% and
0.70%, respectively; see TABLE 1 ). Aspirin was
non-inferior to rivaroxaban (p<0.001) but not
superior (p=0.84) for the prevention of post-
operative proximal DVT or PE.
One death occurred in the aspirin group
because of PE; the patient had undergone
TKA, and the death occurred 31 days after
randomization and 17 days after completion
of aspirin prophylaxis.
Major bleeding events (including major
or clinically relevant non-major bleeding;
primary safety endpoint) were reported by
eight patients (0.47%) in the aspirin group and
five patients (0.29%) in the rivaroxaban group
(difference = 0.18 percentage points; 95% CI
–0.65-0.29; p=0.42). Rates of the combined
endpoint of major bleeding and clinically
relevant non-major bleeding also were similar
between the two cohorts: 22 patients (1.29%) in
the aspirin-treated group and 17 (0.99%) in the
rivaroxaban-treated group (difference = 0.30
percentage points; 95% CI –1.07-0.47; p=0.43).
There were no significant differences in
rates of thromboembolic events or bleeding
complications in the THA or TKA subgroups
treated with aspirin or rivaroxaban.
Among the 855 patients who were receiving
long-term aspirin therapy at randomization,
rates of VTE, major bleeding, and clinically
relevant non-major bleeding outcomes were
similar to outcomes in the 2,569 patients who
were not receiving such therapy (see TABLE 2 ).
This finding “suggests that there was no
benefit of adding aspirin 81 mg to either aspi-
rin or rivaroxaban prophylaxis,” the researchers
reported. “However, there were suggestions of
more major and clinically relevant non-major
bleeding among patients in the long-term as-
pirin subgroup, particularly among those who
had been assigned to the [aspirin] group and
… were receiving a second daily dose of aspirin
prophylaxis.”
Patient recruitment
frequently
occurred
TABLE 1. Primary Efficacy and Safety
postoperatively, which the
Outcome
Rivaroxaban
Aspirin
p Value
authors noted as a limitation
(n=1,717)
(n=1,707)
of the study. In addition,
VTE
12 (0.70%)
11 (0.64%)
most bleeding events that
PE
6 (0.35%)
5 (0.29%)
were related to surgical-site
0.84
Proximal DVT
4 (0.23%)
4 (0.23%)
bleeding occurred early after
randomization, making it
PE or proximal DVT
2 (0.12%)
2 (0.12%)
difficult to determine whether
Major bleeding
5 (0.29%)
8 (0.47%)
0.42
bleeding was predominantly
Any bleeding
17 (0.99%)
22 (1.29%)
0.43
related to the initial course
VTE = venous thromboembolism; PE = pulmonary embolism; DVT = deep vein thrombosis
of postoperative rivaroxaban,
trial medication (rivaroxaban
vs. aspirin), or a combination
TABLE 2. Subgroup Analysis of Primary Outcomes, According to Use of
of both.
Long-Term Aspirin Therapy
The corresponding authors
Outcome
Long-Term Aspirin Therapy
No Long-Term Aspirin Therapy
report no financial conflicts.
Rivaroxaban
(n=429) Aspirin
(n=426) p Value Rivaroxaban
(n=1,288) Aspirin
(n=1,281) p Value
VTE 3 (0.70%) 3 (0.70%) 1.00 9 (0.70%) 8 (0.62%) 1.00
Major bleeding 1 (0.23%) 4 (0.94%) 0.22 4 (0.31%) 4 (0.31%) 1.00
Any bleeding 5 (1.17%) 8 (1.88%) 0.42 12 (0.93%) 14 (1.09%) 0.70
REFERENCE
Anderson DR, J Murnaghan, SR Kahn, et al. Aspirin
or rivaroxaban for VTE prophylaxis after hip or knee
arthroplasty. N Engl J Med. 2018;378:699-707.
VTE =