National Trends in Deep Vein Thrombosis following Total Knee and Total Hip Replacement in the United States

Accepted Manuscript National Trends in Deep Vein Thrombosis Following Total Knee and Total Hip Replacement in the USA Anahita Dua, MD, MS, MBA, Sapan S. Desai, MD, PhD, MBA, Cheong J. Lee, MD, Jennifer A. Heller, MD PII:

S0890-5096(16)30635-5

DOI:

10.1016/j.avsg.2016.05.110

Reference:

AVSG 2949

To appear in:

Annals of Vascular Surgery

Received Date: 4 January 2016 Revised Date:

5 May 2016

Accepted Date: 11 May 2016

Please cite this article as: Dua A, Desai SS, Lee CJ, Heller JA, National Trends in Deep Vein Thrombosis Following Total Knee and Total Hip Replacement in the USA, Annals of Vascular Surgery (2016), doi: 10.1016/j.avsg.2016.05.110. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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National Trends in Deep Vein Thrombosis Following Total Knee and Total Hip Replacement in the USA

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Anahita Dua MD, MS, MBA1, Sapan S. Desai MD, PhD, MBA2, Cheong J. Lee, MD1, Jennifer A. Heller MD3

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1. Division of Vascular Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI 2. Department of Vascular Surgery, Southern Illinois University, Springfield, IL 3. Department of Surgery, Johns Hopkins University, Baltimore, MA

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Oral Presentation at the Eastern Vascular Society (EVS) 29th Annual Meeting, September 24th-26th, 2015, Baltimore, MA

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No conflicts of interest or financial disclosures

Corresponding Author: Jennifer A. Heller, MD Assistant Professor of Vascular Surgery 600 N. Wolfe Street Sheikh Zayed Tower Baltimore, MD 21287 410-550-8346 [email protected]

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Abstract:

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Introduction:

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(THR) are associated with an increased risk of deep vein thrombosis (DVT). Advances in

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DVT prophylaxis over the past decade have led to a decrease in DVT-related morbidity,

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but gender, racial, and other demographic factors that contribute to a higher risk of DVT

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are incompletely characterized. This study aimed to determine the incidence of DVT over

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the past decade and identify factors that were associated with an increased risk of DVT.

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Methods: Patients who underwent TKR or THR between 2001 and 2011 were identified

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using the National Inpatient Sample (NIS). For patients who developed a DVT, their

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demographics (including age, gender, and race), comorbidities, and subsequent outcomes

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(including length of stay [LOS] and mortality) were determined. Differences between

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patients who developed a DVT and those who did not were determined using multivariate

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regression analysis. A Mann-Kendall analysis was done to evaluate all trends.

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Results: Between 2001 and 2011, a total of 1.1 million patients underwent TKR, and

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550,000 underwent THR. The overall incidence of DVT decreased for TKR from 0.86%

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in 2001 to 0.45% in 2011, and decreased for THR from 0.55% to 0.24% for the same

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time period. Patients who developed a DVT following TKR were older (67.7 vs. 66.8,

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P<0.001), more likely to be African American (P<0.001), and more likely to have

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significant comorbidities including congestive heart failure, peripheral artery disease, and

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end stage renal disease. Findings were similar for patients who developed a DVT

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following THR. Mortality was significantly greater for patients who developed a DVT

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(0.4% following TKR and 1.7% for THR), with an almost double LOS.

knee

replacement

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total

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ACCEPTED MANUSCRIPT 3 Conclusions: A focus on DVT prophylaxis may have decreased national rates of

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DVT following TKR and THR. Older patients, African Americans, and patients with

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more co-morbidities appear to be especially at risk for DVT. Mortality is almost 4 to 8

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times higher for patients with DVT and LOS is double. A focus on DVT prophylaxis and

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perhaps more aggressive management of the at-risk population may further help decrease

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the rate of DVT.

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Introduction:

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thromboembolism (VTE).

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patients with deep venous thrombosis (DVT) will develop post-thrombotic syndrome and

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up to 33% of patients will manifest a pulmonary embolus (PE). Further, mortality

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associated with VTE is staggering: approximately 100,000 Americans each year die from

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the manifestations of venous thromboembolic disease.1

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Risk factors for DVT include increasing age, any surgery (with the highest incidence in

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orthopedic intervention), mobility status, trauma, and hypercoagulable states. Guidelines

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from the American College of Chest Physicians (ACCP) have detailed guidelines

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regarding prevention and management of venous thromboembolism.2 Over the previous

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decade there has been an increase in both awareness and DVT prophylaxis within

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hospitals especially with DVT being classified as a preventable event. Current accepted

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medical therapy for patients with VTE is anticoagulation.3

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It has been well established that joint replacement procedures carry a high risk of VTE

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associated events. As a result, the ACCP guidelines recommend thromboprophylaxis,

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using low molecular weight heparin (LMWH) and Factor Xa Inhibitors. According to the

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National Quality Forum (NQF) and the Centers for Medicare & Medicaid Services

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(CMS), DVT after total knee replacement (TKR) and total hip replacement (THR) is

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considered a “nonreimbursable serious hospital-acquired condition” (HACs). The CMS

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adopted the nonreimbursement policy for certain HACs including DVT in TKR and THR

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to motivate hospitals to accelerate improvements in patient safety and limit the hospitals’

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ability to bill Medicare for this complication.3-5

Each year, 1-2 patients per 1000 in the United States are diagnosed with venous

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The natural history of VTE is not benign: over 50% of

ACCEPTED MANUSCRIPT 5 As the United States continues to witness an exponential rise in its elderly population,

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associated procedures such as total joint operations, will likely continue to increase.

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Increased age carries an increased risk of VTE, but as well, associated comorbidity with

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the use of anticoagulation is also increased. Therefore additional data on the risk and

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proper treatment of VTE following THR and TKR is essential for improved clinical

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outcomes. This study aimed to describe the national trend of DVT after TKR and THR

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and detail risk factors associated with DVT.

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Methods:

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Database and Selection

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A retrospective analysis was completed using the National Inpatient Sample (NIS), a part

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of the Health Care Utilization Project (HCUP) that is maintained by the Agency for

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Healthcare Research and Quality (AHRQ). The NIS is the largest all-payer inpatient

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database and includes a stratified 20% random sample of all nonfederal inpatient hospital

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admissions throughout the United States. Clinical records between 2001 and 2011 were

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derived using the ninth revision of the International Classification of Diseases (ICD-9)

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diagnosis and procedure codes to ensure that the sample included patients who underwent

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TKR (8154), THR (8151) and those who sustained DVT (4538, 4539, 45340, 45341,

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45342, 45350, 45351, 45352).

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Variables

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Independent variables included age, gender, diagnosis-related group (DRG) mortality

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risk, DRG severity of illness, race and comorbidities. Outcomes included length of stay

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(LOS), rate of DVT per year, inpatient mortality.

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ACCEPTED MANUSCRIPT 6 Statistical Analysis

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Statistical analysis was completed using analysis of variance (ANOVA) for continuous

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variables (i.e. age) and chi-squared for categorical variables (i.e. gender, race, and

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mortality). The Mann-Whitney U test was used for LOS and total charges. A multivariate

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logistic regression model adjusted for age, gender, DRG mortality risk, DRG severity of

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illness, and hospital covariates was developed. Data analysis and management were

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completed using the IBM SPSS software package (SPSS version 22.0, SPSS Inc.,

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Chicago, IL, USA). Statistical significance was set at a probability of P < 0.05.

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Results:

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Over the 10 year study period, 1.1 million total knee replacements TKR and 550,000 total

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hip replacements THR were performed.

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TKR

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From 2001 to 2011, the rates of TKR rose from 62,709 to 133620. However, the rate of

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DVT occurring post TKR procedure decreased from 0.86% to 0.45% (Table 1). Patients

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who underwent TKR and developed a DVT were more likely to be older (67.7 +/- 10.4

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years vs 66.8 +/- 10.5 years, p<0.001), have a higher DRG severity of illness score (2.4

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+/- 0.6 vs 1.5 +/- 0.6, p<0.001) and have an higher incidence of comorbidities including

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congestive heart failure (CHF) (4.6% vs 2.6%, p<0.001), peripheral artery disease (PAD)

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(2.3% vs 1.6%, P<0.001), and end stage renal disease (ESRD) (2.0% vs 1.4%, p<0.001).

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Patients with DVT were more likely to die in hospital (0.4% vs 0.1%, p<0.001) and had

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longer LOS (6.3 +/- 4.4 days vs 3.7 +/- 1.9, P<0.001). African Americans are 1.3 times

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more likely to have DVT after TKR compared to Caucasians (Table 2).

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THR

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ACCEPTED MANUSCRIPT 7 From 2001 to 2011 the rates of THR rose from 38,896 to 63,611. However, the rate of

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DVT occurring post THR decreased from 0.55% to 0.24% (Table 1). Patients who

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underwent THR and developed a DVT were more likely to be older (69.4 +/- 12.7 years

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vs 65.6 +/- 13.1 years, p<0.001), have a higher DRG severity of illness score (3.0 +/- 0.5

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vs 2.2 +/- 0.7, p<0.001) and have an higher incidence of comorbidities including

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congestive heart failure (CHF) (8.6% vs 2.9%, p<0.001), peripheral artery disease (PAD)

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(3.1% vs 1.9%, P<0.001), and end stage renal disease (ESRD) (4.5% vs 1.7%, p<0.001).

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Patients with DVT were more likely to die in hospital (1.7% vs 0.2%, p<0.001) and had

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longer LOS (8.2 +/- 8.0 days vs 3.9 +/- 2.5, P<0.001). African Americans are 2.2 times

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more likely to have DVT after THR compared to Caucasians (Table 3).

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Discussion:

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DVT after TKR and THR is common but classified as a relatively preventable event by

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the CMS. This has significant implications for hospital reimbursement. Furthermore,

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DVT is associated with both long term morbidity and mortality. Prevention of DVT in

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the TKR and THR patient population is based on two guidelines that detail DVT

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prophylaxis: the ACCP and the American Academy of Orthopedic Surgeons (AAOS).2-5

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Both guidelines base their recommendations on the fact that a history of previous venous

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thromboembolism predicts a higher risk of another VTE with hip or knee replacement

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surgery but neither guidelines is clear on how much of an impact other risk factors

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including obesity, smoking status, medications, thrombophilia may impact risk of VTE.

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Current recommendations state that in patients without a history of VTE,

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mechanical/compressive devices or a pharmacologic agent should be employed.2-7

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However, the duration and intensity of the therapeutic regimen have not been established

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ACCEPTED MANUSCRIPT 8 and left to physician preference. In patients with a VTE history both a mechanical

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compression devices and a pharmacologic agent are recommended but again the duration

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and intensity are not detailed clearly. No specific DVT prophylaxis recommendations

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have been published and there are a variety of “pharmacologic agents” (aspirin, plavix,

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anticoagulants) that may be used under the same guidelines. Furthermore, in patients

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without a history of VTE, essentially any preventive therapy from a mechanical device,

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to aspirin, low molecular weight heparin, unfractionated heparin, fondaparinux, warfarin

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or rivaroxaban – at any dose and for any length of time are acceptable options. For

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patients with a history of VTE a mechanical device and some pharmacologic agent

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(aspirin,

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fondaparinux, or warfarin) may be administered with any dose, frequency and duration

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seen fit by the surgeon.2-7

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There has been a significant increase in the uptake of DVT prophylaxis administration in

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the USA may be responsible for the decreased rates of DVT in this high risk group of

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THR and TKR patients. Our study found that while the incidence of TKR and THR

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operations have increased overall in the USA from 2001 to 2011, the rate of DVT has

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more than halved over the decade for both TKR (0.86% to 0.45%) and THR (0.55% to

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0.24%) (Figure 1).

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Stratton and colleagues6 reported in a multicenter study with 1907 participants that the

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thromboprophylaxis rate received by patients undergoing THR and TKR is 84% and

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76%, respectively. Implementation of thromboprophylaxis measures yielded decreased

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rates of DVT in THR and TKR patients.6 Heit et al.8 demonstrated that the incidence of

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VTE complications, specifically PE, was approximately 50% in postoperative patients

molecular

weight

heparin,

unfractionated heparin,

rivaroxaban,

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ACCEPTED MANUSCRIPT 9 who did not receive thromboprophylaxis.8 Eikelboom et al.7 added that it was not only

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the administration of prophylaxis but the duration that played an integral role in

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decreasing the incidence of symptomatic DVT post THR and TKR surgery. Markovic-

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Denic et al.9 prospectively demonstrated that the average duration for patients received

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thromboprophylaxis was 18.5 ± 9.1 days but patients who received prophylaxis for more

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than 21 days had lower thromboembolic complications.9

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discuss duration or intensity of DVT prophylaxis. While our study was unable to

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ascertain the duration or intensity of prophylaxis, other demographic risk factors

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including gender, age, and race were evaluated to determine if DVT rates could decrease

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further if high risk populations were perhaps treated more aggressive. African American

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patients who were older with more co-morbidities were found to be at highest risk of

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DVT developed in our study. This in turn was associated with increased in-patient

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mortality and length of stay. Increased age is a known risk factor for DVT and ethnic

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associations with the propensity to develop DVT are being studied. A recent study found

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that African ethnicity is associated with an increased risk of both first and recurrent VTE

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based on increased levels of thrombin generation when compared to Caucasians.10

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Limitations:

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This study is limited by its retrospective design and utilization of a large, de-identified

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database. ICD-9 coding has inherent limitations however the strength of this study lies in

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its power given the large sample size. The NIS is a large database but is limited to in-

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hospital data and does not allow for long term follow up in patients who are discharged

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and re-admitted. Hence, patient who were discharged after THR and TKR who were re-

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Current guidelines do not

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admitted with DVT were not captured in this database. Another limitation is the reliance

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on ICD-9 coding.

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Conclusion:

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A

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DVT following TKR and THR as rates for DVT post both these procedures has decreased

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by 50%. Older patients, African Americans, and patients with more co-morbidities appear

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to be especially at risk for DVT. Mortality is almost 4 to 8 times higher for patients with

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DVT and LOS is double. A focus on DVT prophylaxis and perhaps more aggressive

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management of the at-risk population may help decrease the rate of DVT further.

prophylaxis

may

have

decreased

national

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focus

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References: 1. Enders JM, Burke JM, Dobesh PP. Prevention of venous thromboembolism in acute medical illness. Pharmacotherapy. 2002;22(12):1564-78. 2. Maletis GB, Inacio MC, Reynolds S, Funahashi TT: Incidence of symptomatic venous thromboembolism after elective knee arthroscopy. J Bone Joint Surg Am 2012, 94:714–720. 3. The ACCP guidelines for thromboprophylaxis in total hip and knee arthroplasty. Orthopedics 2009, 32:67–73. 4. Nicolaides AN, Breddin HK, Fareed J, Goldhaber S, Haas S, Hull R, et al. Prevention of venous thromboembolism. International Consensus Statement. Guidelines compiled in accordance with the scientific evidence. Int Angiol. 2001;20(1):1-37. 5. Geerts WH, Bergquist D, Pineo G, Heit JA, Samama CM, Lassen MR et al (2008) Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 133(6 Suppl):381S–453S 6. Stratton MA, Anderson FA, Bussey HI, Caprini J, Comerota A, Haines ST, et al. Prevention of venous thromboembolism: adherence to the 1995 American College of Chest Physicians consensus guidelines for surgical patients. Arch Intern Med. 2000;160(3):334-40 7. Eikelboom JW, Quinlan DJ, Douketis JD. Extended-duration prophylaxis against venous thromboembolism after total hip or knee replacement: a metaanalysis of the randomised trials. Lancet. 2001;358(9275):9-15. 8. Heit JA. The epidemiology of venous thromboembolism in the community. Arterioscler Thromb Vasc Biol. 2008 Mar;28(3):370-2. 9. Markovic-Denic L, Zivkovic K, Lesic A, Bumbasirevic V, Dubljanin-Raspopovic E, Bumbasirevic M. Risk factors and distribution of symptomatic venous thromboembolism in total hip and knee replacements: prospective study. Int Orthop. 2012 Jun;36(6):1299-305. doi: 10.1007/s00264-011-1466-5. Epub 2012 Jan 4. 10. Roberts LN, Patel RK, Chitongo P, Bonner L, Arya R. African-Caribbean ethnicity is associated with a hypercoagulable state as measured by thrombin generation. Blood Coagul Fibrinolysis. 2013 Jan;24(1):40-9.

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Table 1: 0.86% 0.82% 0.64% 0.84% 0.66% 0.55% 0.56% 0.57% 0.47% 0.41% 0.45%

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335 336 337 338 339 340 341 342 343 344 345 346 347 348 349 350 351 352 353 354 355 356 357 358 359 360 361 362 363 364 365

Rate of DVT

Sample Size THR 38,896 42,136 41,752 46,486 48,562 46,954 52,079 56,484 56,452 60,715 63,611

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2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

Sample Size TKR 62,709 73,374 78,959 88,724 101,779 102,278 113,606 125,903 122,753 132,668 133,620

Rate of DVT 0.55% 0.45% 0.38% 0.46% 0.42% 0.39% 0.33% 0.34% 0.27% 0.24% 0.24%

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Table 2: TKR with DVT 67.7 +/- 10.4 1.5 +/- 0.7 2.4 +/- 0.6 4.6% 2.3% 2.0%

0.1%

0.4%

3.7 +/- 1.9

6.3 +/- 4.4

Significance P<0.001 P<0.001 P<0.001 P<0.001 P<0.01 P<0.01 P<0.001

P<0.001

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368 369 370 371 372 373 374 375 376 377 378 379 380 381 382 383 384 385 386 387 388 389 390 391 392 393 394 395 396 397 398 399 400 401

TKR no DVT 66.8 +/- 10.5 1.2 +/- 0.5 1.5 +/- 0.6 2.6% 1.6% 1.4%

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Variable Age DRG risk of mortality DRG severity of illness CHF PAD ESRD Outcomes Mortality LOS (mean +/- SD)

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Table 3: TKR with DVT 69.4 +/- 12.7 1.8 +/- 0.9

Significance P<0.001 P<0.001

2.2 +/- 0.7

3.0 +/- 0.5

P<0.001

2.9% 1.9% 1.7%

8.6% 3.1% 4.5%

0.2% 3.9 +/- 2.5

1.7% 8.2 +/- 8.0

P<0.001 P<0.001 P<0.001

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404 405 406 407 408 409 410 411 412 413 414 415 416 417 418 419 420 421 422 423 424 425 426 427 428 429 430 431 432 433 434 435 436

TKR no DVT 65.6 +/- 13.1 1.2 +/- 0.5

P<0.001 P<0.001

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Variable Age DRG risk of mortality DRG severity of illness CHF PAD ESRD Outcomes Mortality LOS (mean +/- SD)

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Figure 1: 1

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0.4 0.3 0.2 0.1 0

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2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

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TKR THR