The Journal of Arthroplasty xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
The Journal of Arthroplasty journal homepage: www.arthroplastyjournal.org
Direct Costs of Aspirin versus Warfarin for Venous Thromboembolism Prophylaxis after Total Knee or Hip Arthroplasty Christina J. Gutowski, MD MPH a, Benjamin M. Zmistowski, MD a, Jess H. Lonner, MD b, James J. Purtill, MD c, Javad Parvizi, MD c a b c
Department of Orthopaedic Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania Rothman Institute for Orthopaedics, Sewell, New Jersey Rothman Institute for Orthopaedics, Philadelphia, Pennsylvania
a r t i c l e
i n f o
Article history: Received 2 August 2014 Accepted 13 April 2015 Available online xxxx Keywords: cost analysis venous thromboembolism prophylaxis aspirin warfarin total joint arthroplasty
a b s t r a c t Interest in aspirin as an alternative strategy for venous thromboembolism prophylaxis after arthroplasty has grown, as studies have suggested improved clinical efficacy and lower complication rates with aspirin compared to warfarin. The goal of this study was to compare the direct costs of an episode of arthroplasty care, when using aspirin instead of warfarin. The charts of patients who either received aspirin or warfarin after arthroplasty from January 2008 to March 2010 were retrospectively reviewed. Charges were recorded for their index admission, and for subsequent admissions related to either VTE or complications of prophylaxis. Multivariate analysis revealed that aspirin was an independent predictor of decreased cost of index hospitalization, and total episode of care charges, achieved largely through a shorter length of hospitalization. © 2015 Elsevier Inc. All rights reserved.
There is a general consensus among clinicians that some method of VTE prophylaxis is appropriate after total joint arthroplasty, but even the most recent American Academy of Orthopaedic Surgeons (AAOS) guidelines are unable to make a recommendation with respect to selection of a specific prophylaxis regimen [1]. The pharmacologic agent selected must strike a balance between optimization of anticoagulation and minimization of bleeding risk, as post-operative bleeding due to overly-aggressive VTE prophylaxis is associated with serious adverse events such as hematoma formation, periprosthetic joint infection, and hemorrhage at distant sites which can be catastrophic [2,3]. In addition to the clinical aspects of this decision, in today’s healthcare paradigm the financial implications of decisions like this are becoming more heavily scrutinized. Warfarin continues to be used frequently by orthopedic surgeons because of its long track record as an effective VTE prophylaxis, as well as reversibility in the event of hemorrhage [2]. Interest in aspirin as an alternative to the traditional pharmacologic anticoagulants has grown over the recent years, because of its proven efficacy and convenience, as no monitoring of this agent is required [4,5]. Aspirin is now recognized by the American College of Chest Physicians as an acceptable One or more of the authors of this paper have disclosed potential or pertinent conflicts of interest, which may include receipt of payment, either direct or indirect, institutional support, or association with an entity in the biomedical field which may be perceived to have potential conflict of interest with this work. For full disclosure statements refer to http://dx.doi.org/10.1016/j.arth.2015.04.048. Reprint requests: Christina J. Gutowski, MD, MPH, Department of Orthopaedic Surgery, Thomas Jefferson University Hospital, 1025 Walnut St., College Building Room 516, Philadelphia, PA 19107.
VTE prophylaxis modality [6], and several studies have shown improvement in rates of symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE), wound drainage, and mean length of hospital stay when aspirin was utilized compared to warfarin [7]. This study aims to determine the financial implications of using aspirin instead of warfarin in terms of direct costs associated with a patient’s episode of care. There are several possible methods to employ when analyzing the cost of a medical intervention. Recently, cost–utility analyses based on Markov modeling have been utilized in the orthopedic literature to evaluate the economic implications of various interventions [8–10]. In consideration of current initiatives toward a bundled payment method of reimbursement for total joint arthroplasty, we propose a contrasting framework for this cost analysis: direct charges for care within the 90day global window of service will be compared. With this method, conclusions can be drawn that are more relevant to current trends in reimbursement and to negotiations regarding allocation of a single global payment to an institution.
Patients and Methods Following local institutional board approval, two study groups were formed for this analysis from January 2008 to March 2010: those administered warfarin and those administered aspirin for VTE prophylaxis following total knee and hip arthroplasty. All patients used pneumatic compression devices during their hospital stay. Total joint arthroplasty was performed by surgeons with arthroplasty fellowship training using regional anesthesia.
http://dx.doi.org/10.1016/j.arth.2015.04.048 0883-5403/© 2015 Elsevier Inc. All rights reserved.
Please cite this article as: Gutowski CJ, et al, Direct Costs of Aspirin versus Warfarin for Venous Thromboembolism Prophylaxis after Total Knee or Hip Arthroplasty, J Arthroplasty (2015), http://dx.doi.org/10.1016/j.arth.2015.04.048
2
C.J. Gutowski et al. / The Journal of Arthroplasty xxx (2015) xxx–xxx
The choice of VTE prophylaxis was at the discretion of the treating surgeon. Enteric coated aspirin was dosed at 325 milligrams twice daily while warfarin was dosed with a target international normalized ratio (INR) between 1.5 and 1.8. Both aspirin and warfarin were prescribed for the first six postoperative weeks. For each admission, inpatient charges were collected by line-item and aggregated for a total cost of admission. In addition, subsequent admissions related to either VTE or complications of VTE prophylaxis were identified. Such causes for readmission included acute superficial or deep infections, bleeding, drainage, kidney injury, cardiopulmonary events, deep venous thrombosis (DVT), or pulmonary embolism (PE). Charges from these readmissions were collected, aggregated, and added to the index hospitalization to represent the entire cost of care. To quantify the overall health of these patients, the Deyo modification [11] of the Charlson Comorbidity Index [12] was utilized. To adjust for any differences in length-of-stay secondary to surgeon or day of the week, both of these variables were collected and analyzed. The aspirin and warfarin cohorts were compared for their respective incidence of VTE-related complications, incidence of VTE related readmissions, length of hospitalization, charges for primary hospitalization, and total charges for the episode of care. To assess differences between the cohorts for continuous variables, a Student’s t-test was utilized. When comparing groups with nonparametric variables, a Mann–Whitney U test was utilized to compare the continuous variables. For dichotomous variables, a Chi-squared analysis versus Fisher’s exact test was used to compare groups with greater than versus less than 5 events in either group, respectively. To account for confounding variables, multivariate analysis for cost variables was performed. This consisted of linear regression with inclusion of demographic and surgical variables, as well as VTE prophylaxis method, and other variables described above (Table 1) as independent variables. Non-parametric data was log-transformed prior to inclusion in the multivariate analysis. For this analysis, data normality was assessed by review of skewness (b 2) and kurtosis (b12). Statistical analysis was performed with SPSS version 20.0 (Chicago, IL). Results The two cohorts combined for 4951 patients with 5372 admissions (2738 for THA and 2634 for TKA). These patients had an average age of 64 years (range: 17–99 years) and 2404 were males (44.8%; 2404/ 5372). Of this group, 1213 (22.6%; 1213/5372) received aspirin as their VTE chemoprophylaxis. Patients receiving aspirin were younger (P b 0.001), more often male (P = 0.002), had lower body mass index (P = 0.02), more often undergoing hip arthroplasty (P b 0.001), had fewer simultaneous bilateral primary arthroplasties (P b 0.001), had fewer revision arthroplasties (P b 0.001), were more often operated upon in the first three days of the work week (P b 0.001), and were healthier (P = 0.006; Table 1). Table 1 Baseline Characteristics of All Patients Receiving Either Aspirin or Warfarin after Total Joint Arthroplasty.
Age Male (%) BMI Revision arthroplasty (%) TKA (%) Simultaneous bilateral (%) Thursday or Friday surgery (%) Charlson Index (%) 0 1 2 ≥3
Aspirin (n = 1213)
Warfarin (n = 4159)
P Value
59.9 590 (48.6%) 29.7 424 (35%) 424 (35%) 14 (1.2%) 25 (2.1%)
64.4 1814 (43.6%) 30.4 2210 (53.1%) 2210 (53.1%) 183 (4.4%) 912 (21.9%)
b0.001 0.002 0.02 b0.001 b0.001 b0.001 b0.001
1029 (88.5%) 116 (10%) 15 (1.3%) 3 (0.3%)
3432 (84%) 536 (13.1%) 102 (2.5%) 17 (0.4%)
0.006
Table 2 Results of Univariate Analysis Comparing Aspirin and Warfarin Groups. The Warfarin Group Suffered Higher Rates of Postoperative Complications, Readmissions, Length of Stay, and Charges.
Length of stay Complication (%) DVT PE Hematoma/seroma Cardiovascular Readmission Index hospitalization charges Total charges
Aspirin (n = 1213)
Warfarin (n = 4159)
P Value
2.6 days 25 (2.1%) 6 (0.5%) 3 (0.2%) 1 (0.02%) 0 (0%) 11 (0.9%) $53,453.47 $54,181.37
3.7 days 241 (5.8%) 49 (1.2%) 62 (1.5%) 21 (0.5%) 12 (0.3%) 89 (2.1%) $63,718.60 $66,054.54
b0.001 b0.001 0.04 b0.001 0.04 0.06 0.005 b0.001 b0.001
Patients receiving aspirin for VTE prophylaxis had a decreased length of stay (P b 0.001), decreased incidence of PE (P b 0.001), decreased incidence of DVT (P = 0.05), decreased incidence of all complications related to VTE prophylaxis (P b 0.001), and decreased incidence of readmission related to VTE prophylaxis (P = 0.005; Table 2). An episode of care associated with the aspirin cohort resulted in average total charges of $54,181 (95% CI: $53,157–55,206), compared to $66,054 (95% CI: $64,502–67,607) for patients receiving warfarin (P b 0.001). The index hospitalization averaged charges of $53,453 (95% CI: $52,602–54,304) for aspirin patients compared to $63,719 (95% CI: $62,479–64,958) for warfarin patients (P b 0.001). When adjusting for age, surgeon, day of surgery, year of surgery, Charlson index, joint, revision versus primary, simultaneous bilateral versus unilateral, body mass index, knee versus hip arthroplasty, and gender, aspirin was an independent predictor of decreased total charges (B = −$5161; P = 0.03) as well as decreased cost of index hospitalization (B = −$4362; P = 0.02) (Table 3). When controlling for length of stay as well as the above listed variables, the aspirin strategy was no longer a significant predictor of lower cost. A secondary analysis was performed to investigate the predictors of length of stay. When adjusting for age, gender, Charlson index, body mass index, day and year of surgery, surgeon, joint replaced (knee versus hip), and revision/primary arthroplasty status, the administration of aspirin was found to be an independent predictor of shorter length of stay (Table 4.) Discussion A recent study comparing the efficacy of aspirin with warfarin demonstrated that aspirin was more effective in prevention of VTE than warfarin and its use was associated with much lower incidence of complications such as bleeding, wound drainage, hematoma formation and so on [7]. Thus, when used in the appropriate patient group, aspirin appears to be an effective modality for prevention of VTE and outperforms warfarin in this context [13]. Another potential advantage for the use of aspirin may be monetary as the drug is inexpensive, carries a lower incidence of associated complications, and reduces length of hospital stay, among the many attributes [5,7]. In an era of costcontainment within healthcare, these findings are timely and valuable, particularly as the volume of arthroplasties performed in the United States continues to rise. In this study aspirin was found to be an independent predictor of lower cost of both the patient’s index hospitalization, as well as the entire episode of care for arthroplasty. Unaccounted for in this study is the actual cost of drugs (six weeks supply of aspirin versus warfarin) and the cost associated with monitoring of the INR and required nursing visits for the warfarin cohort. These costs associated with the two strategies, and the difference between them, are known and are constant. Instead of focusing on these values, this study investigated the financial implications of deciding to administer aspirin or warfarin after arthroplasty, resulting from differential clinical outcomes. If the baseline
Please cite this article as: Gutowski CJ, et al, Direct Costs of Aspirin versus Warfarin for Venous Thromboembolism Prophylaxis after Total Knee or Hip Arthroplasty, J Arthroplasty (2015), http://dx.doi.org/10.1016/j.arth.2015.04.048
C.J. Gutowski et al. / The Journal of Arthroplasty xxx (2015) xxx–xxx
3
Table 3 Results of Multivariate Analysis Comparing the Total Charges and Charges Associated with the Index Arthroplasty Hospitalization for Aspirin and Warfarin Patients.
Variables
B
Age BMI (log) Charlson Index 1 versus 0 N1 versus 0 Year of surgery Simultaneous arthroplasty Main ASA provider Thursday/Friday surgery Total knee arthroplasty Male gender Revision arthroplasty ASA
$221.20 12,957.68
Total Charges
Index Hospitalization
R2 = 0.10
R2 = 0.12
Standardized Coefficient
$9058.72 $11,351.59 $1443.69 $19,942.56 −$2680.86 $477.72 $4700.54 $3149.56 $36,310.18 −$5161.77
P Value
B
0.06 0.007
b0.001 0.59
$178.25 13,804
0.07 0.05 0.02 0.08 −0.03 0.004 0.05 0.03 0.26 −0.05
b0.001 0.001 0.12 b0.001 0.23 0.77 b0.001 0.01 b0.001 0.03
$6863.68 $10,637.44 $1945.40 $20,282.79 −$4362.08 $1671.78 $3537.54 $1840.14 $32,584.12 −$4362.08
drug/INR monitoring costs were included in our model, the difference in episode of care cost would magnify further against warfarin. The two cohorts were markedly different in several demographic characteristics, which could contribute to the differences in cost. Thus, linear regression analyses were performed to account for the confounding variables that could influence cost. The multivariate analysis identified aspirin as an independent predictor for lowering cost of arthroplasty and the entire episode of care. Interestingly, though, when length of stay was included in the analysis, aspirin was no longer an independent protective factor for cost. To further investigate the relationship between aspirin use, length of stay, and cost, a secondary multivariate analysis was performed, using length of stay as the outcome variable. Data displayed in Table 4 suggests that when controlling for many factors driving length of hospitalization, aspirin use is an independent predictor of shorter length of stay. Its impact on overall cost likely is achieved through this association. The explanation for the relationship between aspirin and shorter hospital stay is likely multifactorial. One of the most important factors relates to logistics of warfarin administration. Patients receiving warfarin require blood monitoring which in itself could delay discharge, as most our patients are allowed to leave the hospital the morning after surgery. In addition the “non-therapeutic” levels of INR may have delayed the discharge of some patients. The need for arranging in-house nursing visits for monitoring of the INR may have been another important reason for the longer hospital stay in the warfarin cohort. Finally, patients on warfarin have been shown to have a higher incidence of hematoma formation, wound drainage, and associated complications that could all delay patient discharge from the hospital. Table 4 Results of a Secondary Analysis Examining Drivers of Length of Stay. Utilization of Aspirin Instead of Warfarin Led to a Significantly Lower Length of Stay. Variable
Coefficients (B)
Standardized (Beta)
P Value
Main ASA provider Thursday or Friday surgery ASA Age Male BMI (log) Knee Year of surgery Revision Charlson Index 1 versus 0 N1 versus 0
−0.25 0.29 −0.49 0.03 −0.16 0.28 0.27 −0.16 1.18
−0.04 0.04 −0.08 0.14 −0.03 0.009 0.04 −0.05 0.16
0.05 0.001 b0.001 b0.001 0.02 0.47 b0.001 0.002 b0.001
0.08 0.08
b0.001 b0.001
0.6 1.13
Standardized Coefficient 0.06 0.009 0.07 0.05 0.04 0.1 −0.05 0.02 0.05 0.03 0.29 −0.05
P Value b0.001 0.46 b0.001 b0.001 0.008 b0.001 0.02 0.2 b0.001 0.06 b0.001 0.02
This study does have several limitations. Its retrospective nature introduces selection bias, and prevents the authors from being able to control for all possible confounding factors, despite best attempts made with the multivariate analysis. Patients who suffered complications treated at an outside institution are not included in this analysis, which could potentially bias the results. In any type of Markov or financial analysis like this one, the availability and accuracy of input data limits the study’s validity and generalizability. Despite these weaknesses, the findings of the study are very relevant in the current healthcare climate of cost containment and comparative effectiveness. The relatively large cohort size, the multivariate statistical analyses, and its comparative investigation into both the clinical and financial implications of two VTE prophylaxis strategies were among its strengths. We believe that administration of aspirin is likely to reduce postoperative cost associated with arthroplasty substantially, and can also confer better patient satisfaction. References 1. Mont MA, Jacobs JJ. AAOS clinical practice guideline: preventing venous thromboembolic disease in patients undergoing elective hip and knee arthroplasty. J Am Acad Orthop Surg 2011;19(12):777. 2. Lieberman JR, Pensak MJ. Prevention of venous thromboembolic disease after total hip and knee arthroplasty. J Bone Joint Surg 2013;95:1801. 3. Parvizi J, Ghanem E, Joshi A, et al. Does “excessive” anticoagulation predispose to periprosthetic infection? J Arthroplasty 2007;22(6 Suppl.):24. 4. Lieberman JR, Hsu KW. Prevention of venous thromboembolic disease after total hip and knee arthroplasty. J Bone Joint Surg 2005;87(9):2097. 5. Lotke PA, Lonner JH. The benefit of aspirin chemoprophylaxis for thromboembolism after total knee arthroplasty. Clin Orthop Relat Res 2006;452:175. 6. American College of Chest PhysiciansFalck-Ytter Y, Francis CW, et al. Prevention of VTE in orthopaedic surgery patients: antithrombotic therapy and prevention of thrombosis. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, 141(2 Suppl.). Chest, 9th ed.; 2012. p. e278S. 7. Raphael IJ, Tischler EH, Huang R, et al. Aspirin. An alternative for pulmonary embolism prophylaxis after arthroplasty? Clin Orthop Relat Res 2014;472:482. 8. Bozic KJ, Pui CM, Ludeman MJ, et al. Do the potential benefits of metal-on-metal hip resurfacing justify the increased cost and risk of complications? Clin Orthop Relat Res 2010;468(9):2301. 9. Odum SM, Troyer JL, Kelly MP, et al. A cost-utility analysis comparing the costeffectiveness of simultaneous and staged bilateral total knee arthroplasty. J Bone Joint Surg 2013;95(16):1441. 10. Shearer DW, Kramer J, Bozic KJ, et al. Is hip arthroscopy cost-effective for moroacetabular impingement? Clin Orthop Relat Res 2012;470(4):1079. 11. Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD9-CM administrative databases. J Clin Epidemiol 1992;45:613. 12. Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40(5):373. 13. Parvizi J, Huang R, Raphael IJ, et al. Symptomatic pulmonary embolus after joint arthroplasty: stratification of risk factors. Clin Orthop Relat Res 2014; 472:903.
Please cite this article as: Gutowski CJ, et al, Direct Costs of Aspirin versus Warfarin for Venous Thromboembolism Prophylaxis after Total Knee or Hip Arthroplasty, J Arthroplasty (2015), http://dx.doi.org/10.1016/j.arth.2015.04.048
Contents lists available at ScienceDirect
The Journal of Arthroplasty journal homepage: www.arthroplastyjournal.org
Direct Costs of Aspirin versus Warfarin for Venous Thromboembolism Prophylaxis after Total Knee or Hip Arthroplasty Christina J. Gutowski, MD MPH a, Benjamin M. Zmistowski, MD a, Jess H. Lonner, MD b, James J. Purtill, MD c, Javad Parvizi, MD c a b c
Department of Orthopaedic Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania Rothman Institute for Orthopaedics, Sewell, New Jersey Rothman Institute for Orthopaedics, Philadelphia, Pennsylvania
a r t i c l e
i n f o
Article history: Received 2 August 2014 Accepted 13 April 2015 Available online xxxx Keywords: cost analysis venous thromboembolism prophylaxis aspirin warfarin total joint arthroplasty
a b s t r a c t Interest in aspirin as an alternative strategy for venous thromboembolism prophylaxis after arthroplasty has grown, as studies have suggested improved clinical efficacy and lower complication rates with aspirin compared to warfarin. The goal of this study was to compare the direct costs of an episode of arthroplasty care, when using aspirin instead of warfarin. The charts of patients who either received aspirin or warfarin after arthroplasty from January 2008 to March 2010 were retrospectively reviewed. Charges were recorded for their index admission, and for subsequent admissions related to either VTE or complications of prophylaxis. Multivariate analysis revealed that aspirin was an independent predictor of decreased cost of index hospitalization, and total episode of care charges, achieved largely through a shorter length of hospitalization. © 2015 Elsevier Inc. All rights reserved.
There is a general consensus among clinicians that some method of VTE prophylaxis is appropriate after total joint arthroplasty, but even the most recent American Academy of Orthopaedic Surgeons (AAOS) guidelines are unable to make a recommendation with respect to selection of a specific prophylaxis regimen [1]. The pharmacologic agent selected must strike a balance between optimization of anticoagulation and minimization of bleeding risk, as post-operative bleeding due to overly-aggressive VTE prophylaxis is associated with serious adverse events such as hematoma formation, periprosthetic joint infection, and hemorrhage at distant sites which can be catastrophic [2,3]. In addition to the clinical aspects of this decision, in today’s healthcare paradigm the financial implications of decisions like this are becoming more heavily scrutinized. Warfarin continues to be used frequently by orthopedic surgeons because of its long track record as an effective VTE prophylaxis, as well as reversibility in the event of hemorrhage [2]. Interest in aspirin as an alternative to the traditional pharmacologic anticoagulants has grown over the recent years, because of its proven efficacy and convenience, as no monitoring of this agent is required [4,5]. Aspirin is now recognized by the American College of Chest Physicians as an acceptable One or more of the authors of this paper have disclosed potential or pertinent conflicts of interest, which may include receipt of payment, either direct or indirect, institutional support, or association with an entity in the biomedical field which may be perceived to have potential conflict of interest with this work. For full disclosure statements refer to http://dx.doi.org/10.1016/j.arth.2015.04.048. Reprint requests: Christina J. Gutowski, MD, MPH, Department of Orthopaedic Surgery, Thomas Jefferson University Hospital, 1025 Walnut St., College Building Room 516, Philadelphia, PA 19107.
VTE prophylaxis modality [6], and several studies have shown improvement in rates of symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE), wound drainage, and mean length of hospital stay when aspirin was utilized compared to warfarin [7]. This study aims to determine the financial implications of using aspirin instead of warfarin in terms of direct costs associated with a patient’s episode of care. There are several possible methods to employ when analyzing the cost of a medical intervention. Recently, cost–utility analyses based on Markov modeling have been utilized in the orthopedic literature to evaluate the economic implications of various interventions [8–10]. In consideration of current initiatives toward a bundled payment method of reimbursement for total joint arthroplasty, we propose a contrasting framework for this cost analysis: direct charges for care within the 90day global window of service will be compared. With this method, conclusions can be drawn that are more relevant to current trends in reimbursement and to negotiations regarding allocation of a single global payment to an institution.
Patients and Methods Following local institutional board approval, two study groups were formed for this analysis from January 2008 to March 2010: those administered warfarin and those administered aspirin for VTE prophylaxis following total knee and hip arthroplasty. All patients used pneumatic compression devices during their hospital stay. Total joint arthroplasty was performed by surgeons with arthroplasty fellowship training using regional anesthesia.
http://dx.doi.org/10.1016/j.arth.2015.04.048 0883-5403/© 2015 Elsevier Inc. All rights reserved.
Please cite this article as: Gutowski CJ, et al, Direct Costs of Aspirin versus Warfarin for Venous Thromboembolism Prophylaxis after Total Knee or Hip Arthroplasty, J Arthroplasty (2015), http://dx.doi.org/10.1016/j.arth.2015.04.048
2
C.J. Gutowski et al. / The Journal of Arthroplasty xxx (2015) xxx–xxx
The choice of VTE prophylaxis was at the discretion of the treating surgeon. Enteric coated aspirin was dosed at 325 milligrams twice daily while warfarin was dosed with a target international normalized ratio (INR) between 1.5 and 1.8. Both aspirin and warfarin were prescribed for the first six postoperative weeks. For each admission, inpatient charges were collected by line-item and aggregated for a total cost of admission. In addition, subsequent admissions related to either VTE or complications of VTE prophylaxis were identified. Such causes for readmission included acute superficial or deep infections, bleeding, drainage, kidney injury, cardiopulmonary events, deep venous thrombosis (DVT), or pulmonary embolism (PE). Charges from these readmissions were collected, aggregated, and added to the index hospitalization to represent the entire cost of care. To quantify the overall health of these patients, the Deyo modification [11] of the Charlson Comorbidity Index [12] was utilized. To adjust for any differences in length-of-stay secondary to surgeon or day of the week, both of these variables were collected and analyzed. The aspirin and warfarin cohorts were compared for their respective incidence of VTE-related complications, incidence of VTE related readmissions, length of hospitalization, charges for primary hospitalization, and total charges for the episode of care. To assess differences between the cohorts for continuous variables, a Student’s t-test was utilized. When comparing groups with nonparametric variables, a Mann–Whitney U test was utilized to compare the continuous variables. For dichotomous variables, a Chi-squared analysis versus Fisher’s exact test was used to compare groups with greater than versus less than 5 events in either group, respectively. To account for confounding variables, multivariate analysis for cost variables was performed. This consisted of linear regression with inclusion of demographic and surgical variables, as well as VTE prophylaxis method, and other variables described above (Table 1) as independent variables. Non-parametric data was log-transformed prior to inclusion in the multivariate analysis. For this analysis, data normality was assessed by review of skewness (b 2) and kurtosis (b12). Statistical analysis was performed with SPSS version 20.0 (Chicago, IL). Results The two cohorts combined for 4951 patients with 5372 admissions (2738 for THA and 2634 for TKA). These patients had an average age of 64 years (range: 17–99 years) and 2404 were males (44.8%; 2404/ 5372). Of this group, 1213 (22.6%; 1213/5372) received aspirin as their VTE chemoprophylaxis. Patients receiving aspirin were younger (P b 0.001), more often male (P = 0.002), had lower body mass index (P = 0.02), more often undergoing hip arthroplasty (P b 0.001), had fewer simultaneous bilateral primary arthroplasties (P b 0.001), had fewer revision arthroplasties (P b 0.001), were more often operated upon in the first three days of the work week (P b 0.001), and were healthier (P = 0.006; Table 1). Table 1 Baseline Characteristics of All Patients Receiving Either Aspirin or Warfarin after Total Joint Arthroplasty.
Age Male (%) BMI Revision arthroplasty (%) TKA (%) Simultaneous bilateral (%) Thursday or Friday surgery (%) Charlson Index (%) 0 1 2 ≥3
Aspirin (n = 1213)
Warfarin (n = 4159)
P Value
59.9 590 (48.6%) 29.7 424 (35%) 424 (35%) 14 (1.2%) 25 (2.1%)
64.4 1814 (43.6%) 30.4 2210 (53.1%) 2210 (53.1%) 183 (4.4%) 912 (21.9%)
b0.001 0.002 0.02 b0.001 b0.001 b0.001 b0.001
1029 (88.5%) 116 (10%) 15 (1.3%) 3 (0.3%)
3432 (84%) 536 (13.1%) 102 (2.5%) 17 (0.4%)
0.006
Table 2 Results of Univariate Analysis Comparing Aspirin and Warfarin Groups. The Warfarin Group Suffered Higher Rates of Postoperative Complications, Readmissions, Length of Stay, and Charges.
Length of stay Complication (%) DVT PE Hematoma/seroma Cardiovascular Readmission Index hospitalization charges Total charges
Aspirin (n = 1213)
Warfarin (n = 4159)
P Value
2.6 days 25 (2.1%) 6 (0.5%) 3 (0.2%) 1 (0.02%) 0 (0%) 11 (0.9%) $53,453.47 $54,181.37
3.7 days 241 (5.8%) 49 (1.2%) 62 (1.5%) 21 (0.5%) 12 (0.3%) 89 (2.1%) $63,718.60 $66,054.54
b0.001 b0.001 0.04 b0.001 0.04 0.06 0.005 b0.001 b0.001
Patients receiving aspirin for VTE prophylaxis had a decreased length of stay (P b 0.001), decreased incidence of PE (P b 0.001), decreased incidence of DVT (P = 0.05), decreased incidence of all complications related to VTE prophylaxis (P b 0.001), and decreased incidence of readmission related to VTE prophylaxis (P = 0.005; Table 2). An episode of care associated with the aspirin cohort resulted in average total charges of $54,181 (95% CI: $53,157–55,206), compared to $66,054 (95% CI: $64,502–67,607) for patients receiving warfarin (P b 0.001). The index hospitalization averaged charges of $53,453 (95% CI: $52,602–54,304) for aspirin patients compared to $63,719 (95% CI: $62,479–64,958) for warfarin patients (P b 0.001). When adjusting for age, surgeon, day of surgery, year of surgery, Charlson index, joint, revision versus primary, simultaneous bilateral versus unilateral, body mass index, knee versus hip arthroplasty, and gender, aspirin was an independent predictor of decreased total charges (B = −$5161; P = 0.03) as well as decreased cost of index hospitalization (B = −$4362; P = 0.02) (Table 3). When controlling for length of stay as well as the above listed variables, the aspirin strategy was no longer a significant predictor of lower cost. A secondary analysis was performed to investigate the predictors of length of stay. When adjusting for age, gender, Charlson index, body mass index, day and year of surgery, surgeon, joint replaced (knee versus hip), and revision/primary arthroplasty status, the administration of aspirin was found to be an independent predictor of shorter length of stay (Table 4.) Discussion A recent study comparing the efficacy of aspirin with warfarin demonstrated that aspirin was more effective in prevention of VTE than warfarin and its use was associated with much lower incidence of complications such as bleeding, wound drainage, hematoma formation and so on [7]. Thus, when used in the appropriate patient group, aspirin appears to be an effective modality for prevention of VTE and outperforms warfarin in this context [13]. Another potential advantage for the use of aspirin may be monetary as the drug is inexpensive, carries a lower incidence of associated complications, and reduces length of hospital stay, among the many attributes [5,7]. In an era of costcontainment within healthcare, these findings are timely and valuable, particularly as the volume of arthroplasties performed in the United States continues to rise. In this study aspirin was found to be an independent predictor of lower cost of both the patient’s index hospitalization, as well as the entire episode of care for arthroplasty. Unaccounted for in this study is the actual cost of drugs (six weeks supply of aspirin versus warfarin) and the cost associated with monitoring of the INR and required nursing visits for the warfarin cohort. These costs associated with the two strategies, and the difference between them, are known and are constant. Instead of focusing on these values, this study investigated the financial implications of deciding to administer aspirin or warfarin after arthroplasty, resulting from differential clinical outcomes. If the baseline
Please cite this article as: Gutowski CJ, et al, Direct Costs of Aspirin versus Warfarin for Venous Thromboembolism Prophylaxis after Total Knee or Hip Arthroplasty, J Arthroplasty (2015), http://dx.doi.org/10.1016/j.arth.2015.04.048
C.J. Gutowski et al. / The Journal of Arthroplasty xxx (2015) xxx–xxx
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Table 3 Results of Multivariate Analysis Comparing the Total Charges and Charges Associated with the Index Arthroplasty Hospitalization for Aspirin and Warfarin Patients.
Variables
B
Age BMI (log) Charlson Index 1 versus 0 N1 versus 0 Year of surgery Simultaneous arthroplasty Main ASA provider Thursday/Friday surgery Total knee arthroplasty Male gender Revision arthroplasty ASA
$221.20 12,957.68
Total Charges
Index Hospitalization
R2 = 0.10
R2 = 0.12
Standardized Coefficient
$9058.72 $11,351.59 $1443.69 $19,942.56 −$2680.86 $477.72 $4700.54 $3149.56 $36,310.18 −$5161.77
P Value
B
0.06 0.007
b0.001 0.59
$178.25 13,804
0.07 0.05 0.02 0.08 −0.03 0.004 0.05 0.03 0.26 −0.05
b0.001 0.001 0.12 b0.001 0.23 0.77 b0.001 0.01 b0.001 0.03
$6863.68 $10,637.44 $1945.40 $20,282.79 −$4362.08 $1671.78 $3537.54 $1840.14 $32,584.12 −$4362.08
drug/INR monitoring costs were included in our model, the difference in episode of care cost would magnify further against warfarin. The two cohorts were markedly different in several demographic characteristics, which could contribute to the differences in cost. Thus, linear regression analyses were performed to account for the confounding variables that could influence cost. The multivariate analysis identified aspirin as an independent predictor for lowering cost of arthroplasty and the entire episode of care. Interestingly, though, when length of stay was included in the analysis, aspirin was no longer an independent protective factor for cost. To further investigate the relationship between aspirin use, length of stay, and cost, a secondary multivariate analysis was performed, using length of stay as the outcome variable. Data displayed in Table 4 suggests that when controlling for many factors driving length of hospitalization, aspirin use is an independent predictor of shorter length of stay. Its impact on overall cost likely is achieved through this association. The explanation for the relationship between aspirin and shorter hospital stay is likely multifactorial. One of the most important factors relates to logistics of warfarin administration. Patients receiving warfarin require blood monitoring which in itself could delay discharge, as most our patients are allowed to leave the hospital the morning after surgery. In addition the “non-therapeutic” levels of INR may have delayed the discharge of some patients. The need for arranging in-house nursing visits for monitoring of the INR may have been another important reason for the longer hospital stay in the warfarin cohort. Finally, patients on warfarin have been shown to have a higher incidence of hematoma formation, wound drainage, and associated complications that could all delay patient discharge from the hospital. Table 4 Results of a Secondary Analysis Examining Drivers of Length of Stay. Utilization of Aspirin Instead of Warfarin Led to a Significantly Lower Length of Stay. Variable
Coefficients (B)
Standardized (Beta)
P Value
Main ASA provider Thursday or Friday surgery ASA Age Male BMI (log) Knee Year of surgery Revision Charlson Index 1 versus 0 N1 versus 0
−0.25 0.29 −0.49 0.03 −0.16 0.28 0.27 −0.16 1.18
−0.04 0.04 −0.08 0.14 −0.03 0.009 0.04 −0.05 0.16
0.05 0.001 b0.001 b0.001 0.02 0.47 b0.001 0.002 b0.001
0.08 0.08
b0.001 b0.001
0.6 1.13
Standardized Coefficient 0.06 0.009 0.07 0.05 0.04 0.1 −0.05 0.02 0.05 0.03 0.29 −0.05
P Value b0.001 0.46 b0.001 b0.001 0.008 b0.001 0.02 0.2 b0.001 0.06 b0.001 0.02
This study does have several limitations. Its retrospective nature introduces selection bias, and prevents the authors from being able to control for all possible confounding factors, despite best attempts made with the multivariate analysis. Patients who suffered complications treated at an outside institution are not included in this analysis, which could potentially bias the results. In any type of Markov or financial analysis like this one, the availability and accuracy of input data limits the study’s validity and generalizability. Despite these weaknesses, the findings of the study are very relevant in the current healthcare climate of cost containment and comparative effectiveness. The relatively large cohort size, the multivariate statistical analyses, and its comparative investigation into both the clinical and financial implications of two VTE prophylaxis strategies were among its strengths. We believe that administration of aspirin is likely to reduce postoperative cost associated with arthroplasty substantially, and can also confer better patient satisfaction. References 1. Mont MA, Jacobs JJ. AAOS clinical practice guideline: preventing venous thromboembolic disease in patients undergoing elective hip and knee arthroplasty. J Am Acad Orthop Surg 2011;19(12):777. 2. Lieberman JR, Pensak MJ. Prevention of venous thromboembolic disease after total hip and knee arthroplasty. J Bone Joint Surg 2013;95:1801. 3. Parvizi J, Ghanem E, Joshi A, et al. Does “excessive” anticoagulation predispose to periprosthetic infection? J Arthroplasty 2007;22(6 Suppl.):24. 4. Lieberman JR, Hsu KW. Prevention of venous thromboembolic disease after total hip and knee arthroplasty. J Bone Joint Surg 2005;87(9):2097. 5. Lotke PA, Lonner JH. The benefit of aspirin chemoprophylaxis for thromboembolism after total knee arthroplasty. Clin Orthop Relat Res 2006;452:175. 6. American College of Chest PhysiciansFalck-Ytter Y, Francis CW, et al. Prevention of VTE in orthopaedic surgery patients: antithrombotic therapy and prevention of thrombosis. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, 141(2 Suppl.). Chest, 9th ed.; 2012. p. e278S. 7. Raphael IJ, Tischler EH, Huang R, et al. Aspirin. An alternative for pulmonary embolism prophylaxis after arthroplasty? Clin Orthop Relat Res 2014;472:482. 8. Bozic KJ, Pui CM, Ludeman MJ, et al. Do the potential benefits of metal-on-metal hip resurfacing justify the increased cost and risk of complications? Clin Orthop Relat Res 2010;468(9):2301. 9. Odum SM, Troyer JL, Kelly MP, et al. A cost-utility analysis comparing the costeffectiveness of simultaneous and staged bilateral total knee arthroplasty. J Bone Joint Surg 2013;95(16):1441. 10. Shearer DW, Kramer J, Bozic KJ, et al. Is hip arthroscopy cost-effective for moroacetabular impingement? Clin Orthop Relat Res 2012;470(4):1079. 11. Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD9-CM administrative databases. J Clin Epidemiol 1992;45:613. 12. Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40(5):373. 13. Parvizi J, Huang R, Raphael IJ, et al. Symptomatic pulmonary embolus after joint arthroplasty: stratification of risk factors. Clin Orthop Relat Res 2014; 472:903.
Please cite this article as: Gutowski CJ, et al, Direct Costs of Aspirin versus Warfarin for Venous Thromboembolism Prophylaxis after Total Knee or Hip Arthroplasty, J Arthroplasty (2015), http://dx.doi.org/10.1016/j.arth.2015.04.048
