[Ortho] Venous Thromboembolism Prophylaxis After TKA: Aspirin, Warfarin, Enoxaparin, or Factor Xa Inhibitors?

[Alexander Chelnokov]

Background


There is considerable debate regarding the ideal agent for venous 
thromboembolism (VTE) prophylaxis after TKA. Numerous studies and 
meta-analyses have yet to provide a clear answer and often omit one or 
more of the commonly used agents such as aspirin, warfarin, enoxaparin, 
and factor Xa inhibitors.

Questions/Purposes



Using a large database analysis, we asked: (1) What are the differences 
in VTE incidence in primary TKA after administration of aspirin, 
warfarin, enoxaparin, or factor Xa inhibitors? (2) What are the 
differences in bleeding risk among these four agents? (3) How has use of 
these agents changed with time?



Methods



We queried a combined Humana and Medicare database between 2007 and 
Quarter 1 of 2016, and identified all primary TKAs performed using ICD-9 
and Current Procedural Terminology codes. All patients who had any form 
of antiplatelet or anticoagulation prescribed within 1 year before TKA 
were excluded from our study cohort. We then identified patients who had 
either aspirin, warfarin, enoxaparin, or factor Xa inhibitors prescribed 
within 2 weeks of primary TKA. Each cohort was matched by age and sex. 
Elixhauser comorbidities and Charlson Comorbidity Index for each group 
were calculated. We identified 1016 patients with aspirin, and age- and 
sex-matched 6096 patients with enoxaparin, 6096 patients with warfarin, 
and 5080 patients with factor Xa inhibitors. Using ICD-9 codes, with the 
understanding that patients at greater risk may have had more-attentive 
surveillance, the incidence of postoperative deep venous thrombosis 
(DVT), pulmonary embolism (PE), bleeding-related complications (bleeding 
requiring surgical intervention, hemorrhage, hematoma, hemarthrosis), 
postoperative anemia, and transfusion were identified at 2 weeks, 30 
days, 6 weeks, and 90 days postoperatively. A four-way chi-squared test 
was used to determine statistical significance. Utilization was 
calculated using compound annual growth rate.



Results



There was a difference in the incidence of DVT at 90 days (p< 0.01). 
Factor Xa inhibitors (2.9%) had the lowest incidence of DVT followed by 
aspirin (3.0%) and enoxaparin (3.5%), and warfarin (4.8%). There was a 
difference in the incidence of PE at 90 days (p< 0.01). Factor Xa 
inhibitors (0.9%) had the lowest incidence of PE followed by enoxaparin 
(1.1%), aspirin (1.2%), and warfarin (1.6%). There was a difference in 
the incidence of postoperative anemia at 90 days (p< 0.01). Aspirin 
(19%) had the lowest incidence of postoperative anemia followed by 
warfarin (22%), enoxaparin (23%), and factor Xa inhibitors (23%). There 
was a difference in the incidence of a blood transfusion at 90 days (p< 
0.01). Aspirin (7%) had the lowest incidence of a blood transfusion 
followed by factor Xa inhibitors (9%), warfarin (12%), and enoxaparin 
(13%). There were no differences in bleeding-related complications (p = 
0.81) between the groups. Aspirin use increased at a compound annual 
growth rate of 30%, enoxaparin at 3%, and factor Xa inhibitors at 43%, 
while warfarin use decreased at a compound annual growth rate of -3%.



Conclusions



Factor Xa inhibitors had the highest growth in utilization during our 
study period, followed by aspirin, when compared with enoxaparin and 
warfarin. When selected for the right patient, factor Xa inhibitors 
provided improved VTE prophylaxis compared with enoxaparin and warfarin, 
with a lower rate of blood transfusion. Aspirin provided comparable VTE 
prophylaxis compared with factor Xa inhibitors with improved VTE 
prophylaxis compared with enoxaparin and warfarin with the lowest risk 
of bleeding.



Level of Evidence



Level III, therapeutic study.

https://link.springer.com/article/10.1007%2Fs11999-017-5394-6
Alexander Chelnokov