CLINICAL NEWS
Finding the Best VTE Prophylaxis Options for Patients
Undergoing Total Hip and Knee Replacement
For prophylaxis against venous thrombo-
embolism (VTE) after total hip replace-
ment (THR) or total knee replacement
(TKR), guidelines from the American
College of Chest Physicians have tradi-
tionally recommended fondaparinux or
low-molecular-weight heparin (LMWH)
over aspirin. With emerging evidence
that direct oral anticoagulants (DOACs)
are convenient and effective options for
these patients, the guidelines expanded
the choice to include DOACs and aspirin.
However, the lack of comparative-
effectiveness research for these options
means that there is no clear favorite.
In a literature review published in the
Journal of Thrombosis and Haemostasis,
Alok Kapoor, MD, from the University of
Massachusetts Medical School, and co-
authors analyzed 12 prophylactic regimens
for this patient population, finding that
DOACs have a better safety and efficacy
profile than higher-potency agents such
as fondaparinux, LMWH, and vitamin K
antagonists (VKAs). These newer agents
also did not significantly increase the risk
of hemorrhage.
The researchers conducted a search
of OVID Medline, the Cochrane Library,
and ClinicalTrials.gov to identify 94
English-language, randomized, controlled
trials published between January 1990 and
June 2016 that compared the following
VTE prophylaxis options in the THR and
TKR patient population:
• fondaparinux
• static mechanical options (i.e., com-
pression stockings)
and aspirin performed equivalently, rela-
tive to low LMWH.
For symptomatic DVT, relative to low
LMWH, DOACs led to four-fold fewer
• no antithrombic or mechanical
compression
Most studies (90%) included older
patients with a mean age of >60 years,
and more than half of studies (57%) had
industry sponsorship.
The two largest studies included low
LMWH; because this was the most com-
mon comparator in the studies, it served
as the reference comparator.
For deep vein thrombosis (DVT),
relative to low LMWH, DOACs were the
most effective at preventing VTE, result-
ing in 53 to 139 fewer VTE events per
1,000 patients. Aspirin performed equiva-
lently, relative to low LMWH. The use of
VKA titrated to an INR of 2-3, however,
was associated with 56 percent more DVT
events (48-101 events per 1,000 patients).
“There does not seem to be a compel-
ling reason for professional societies to
continue to suggest [aspirin] as a pro-
phylaxis option for the average patient
undergoing THR and TKR,” the authors
observed. (See TABLE 2 for all outcomes.)
Relative to low LMWH, DOACs dem-
onstrated a trend toward increased hem-
orrhage, resulting in 0.5 to 6 more events
per 1,000 patients, but this association was
not statistically significant (p value not
provided). VKA titrated to an INR of 2-3
TABLE 2.
“There does not seem to be a
compelling reason for professional
societies to continue to suggest
[aspirin].”
• LMWH at twice-daily dosing (high
LMWH)
• LMWH at once-daily dosing (enoxa-
parin 40 mg or dalteparin 5,000 IU/
day; low LMWH)
—ALOK KAPOOR, MD
events, translating to 1.5 to 15 fewer
events per 1,000 patients.
Fondaparinux, direct thrombin
inhibitors, and high LMWH did not have
more favorable safety or efficacy profiles,
compared with low LMWH.
“All other strategies were inferior to
DOACs, except for aspirin,” the authors
concluded, which non-significantly
reduced the risk of hemorrhage compared
with low LMWH (odds ratio = 0.88; 95%
CI 0.35-2.22).
The results of this study diverge
from the evidence used to guide recom-
mendations set forth by CHEST and
the American Academy of Orthopaedic
Surgeons, likely because the societies pri-
oritized prevention of symptomatic VTE
over prevention of a major hemorrhage
selection of prophylaxis options to those
we identified with better profiles,” the
authors concluded.
“Small study numbers and low event
rates limit the conclusions we can draw
about the other options,” the researchers
noted. “Low numbers also prohibit our abil-
ity to make firm conclusions about the rela-
tive effectiveness of prophylaxis options for
preventing non-fatal pulmonary embolism.”
The study also is limited by variations
in the study designs and the small number
of non-industry-sponsored studies, which
could have affected the comparison.
REFERENCE
Kapoor A, Ellis A, Shaffer N, et al. Comparative effectiveness of venous
thromboembolism prophylaxis options for the patient undergoing
total hip and knee replacement: a network meta-analysis. J Thromb
Haemost. 2017;15:284-94.
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