Predicting Pulmonary Embolism in Total Joint Arthroplasty Patients A Pilot Study.

Postoperative venous thromboembolism (VTE) is a common and costly complication following total joint arthroplasty (TJA). Development of a refined thrombophilic screening panel will better equip clinicians to identify patients at high-est risk for developing VTEs. In this pilot study, 62 high-risk TJA recipients who had developed pulmonary emboli (PE) within 90-days of surgery were eligible to participate. Of these patients, 14 were enrolled and subsequently adminis-tered a pre-determined panel of 18 hematologic tests with the aim of identifying markers that are consistently elevated or deficient in patients developing PE. A separate cohort of seven high-risk TJA recipients who did not report a symp-tomatic VTE within 90-days of surgery were then enrolled and Factor VIII and lipoprotein(a) levels were assessed. The most common aberrance was noted in 10 patients (71.4%) who had elevated levels of Factor VIII followed by five patients (35.7%) who had elevated levels of lipoprotein(a). Factor VIII was significantly prevalent (p < 0.001) while lipoprotein(a) failed to achieve statistical significance (p = 0.0708). Of the patients who were within normal limits of Factor VIII, three-fourths were "high-normal" with Fac-tor VIII levels within 5% of the upper limit of normal. This study demonstrates the potential utility of this hematologic panel as part of a perioperative screening protocol aimed at identifying patients at risk for developing VTEs. However, future larger scale studies assessing the capabilities and limitations of our findings are warranted.

Postoperative Vitamin D Surveillance and Supplementation in Revision Total Knee Arthroplasty Patients: A Retrospective Cohort Analysis.

This study was a retrospective cohort analysis of 20 patients who underwent 23 revision total knee arthroplasty procedures in a single geographic region of the United States from January 2015 to February 2023. We analyzed their 25-OH vitamin D levels preoperatively and postoperatively at 1 month, 3 months, 6 months, 1 year, and 2 years. We categorized their supplementation regimens by dose: none, low dose (1000 IU and below), medium dose (1001-5000 IU), and high dose (>5000 IU). We found that there was a high incidence of vitamin D deficiency in this patient population.

Who Are the Anatomic Outliers Undergoing Total Knee Arthroplasty? A Computed Tomography-Based Analysis of the Hip-Knee-Ankle Axis Across 1,352 Preoperative Computed Tomographies Using a Deep Learning and Computer Vision-Based Pipeline.

BACKGROUND: Dissatisfaction after total knee arthroplasty (TKA) ranges from 15 to 30%. While patient selection may be partially responsible, morphological and reconstructive challenges may be determinants. Preoperative computed tomography (CT) scans for TKA planning allow us to evaluate the hip-knee-ankle axis and establish a baseline phenotypic distribution across anatomic parameters. The purpose of this cross-sectional analysis was to establish the distributions of 27 parameters in a pre-TKA cohort and perform threshold analysis to identify anatomic outliers. METHODS: There were 1,352 pre-TKA CTs that were processed. A 2-step deep learning pipeline of classification and segmentation models identified landmark images and then generated contour representations. We used an open-source computer vision library to compute measurements for 27 anatomic metrics along the hip-knee axis. Normative distribution plots were established, and thresholds for the 15th percentile at both extremes were calculated. Metrics falling outside the central 70th percentile were considered outlier indices. A threshold analysis of outlier indices against the proportion of the cohort was performed. RESULTS: Significant variation exists in pre-TKA anatomy across 27 normally distributed metrics. Threshold analysis revealed a sigmoid function with a critical point at 9 outlier indices, representing 31.2% of subjects as anatomic outliers. Metrics with the greatest variation related to deformity (tibiofemoral angle, medial proximal tibial angle, lateral distal femoral angle), bony size (tibial width, anteroposterior femoral size, femoral head size, medial femoral condyle size), intraoperative landmarks (posterior tibial slope, transepicondylar and posterior condylar axes), and neglected rotational considerations (acetabular and femoral version, femoral torsion). CONCLUSIONS: In the largest non-industry database of pre-TKA CTs using a fully automated 3-stage deep learning and computer vision-based pipeline, marked anatomic variation exists. In the pursuit of understanding the dissatisfaction rate after TKA, acknowledging that 31% of patients represent anatomic outliers may help us better achieve anatomically personalized TKA, with or without adjunctive technology.

Assessing Ability for ChatGPT to Answer Total Knee Arthroplasty-Related Questions.

BACKGROUND: Artificial intelligence in the field of orthopaedics has been a topic of increasing interest and opportunity in recent years. Its applications are widespread both for physicians and patients, including use in clinical decision-making, in the operating room, and in research. In this study, we aimed to assess the quality of ChatGPT answers when asked questions related to total knee arthroplasty. METHODS: ChatGPT prompts were created by turning 15 of the American Academy of Orthopaedic Surgeons Clinical Practice Guidelines into questions. An online survey was created, which included screenshots of each prompt and answers to the 15 questions. Surgeons were asked to grade ChatGPT answers from 1 to 5 based on their characteristics: (1) relevance, (2) accuracy, (3) clarity, (4) completeness, (5) evidence-based, and (6) consistency. There were 11 Adult Joint Reconstruction fellowship-trained surgeons who completed the survey. Questions were subclassified based on the subject of the prompt: (1) risk factors, (2) implant/intraoperative, and (3) pain/functional outcomes. The average and standard deviation for all answers, as well as for each subgroup, were calculated. Inter-rater reliability (IRR) was also calculated. RESULTS: All answer characteristics were graded as being above average (ie, a score > 3). Relevance demonstrated the highest scores (4.43 ± 0.77) by surgeons surveyed, and consistency demonstrated the lowest scores (3.54 ± 1.10). ChatGPT prompts in the Risk Factors group demonstrated the best responses, while those in the Pain/Functional Outcome group demonstrated the lowest. The overall IRR was found to be 0.33 (poor reliability), with the highest IRR for relevance (0.43) and the lowest for evidence-based (0.28). CONCLUSIONS: ChatGPT can answer questions regarding well-established clinical guidelines in total knee arthroplasty with above-average accuracy but demonstrates variable reliability. This investigation is the first step in understanding large language model artificial intelligence like ChatGPT and how well they perform in the field of arthroplasty.

Treating Hepatitis C Before Total Knee Arthroplasty is Cost-Effective: A Markov Analysis.

BACKGROUND: Patients who have the hepatitis C virus (HCV) have increased mortality and complication rates following total knee arthroplasty (TKA). Recent advances in HCV therapy have enabled clinicians to eradicate the disease using direct-acting antivirals (DAAs); however, its cost-effectiveness before TKA remains to be demonstrated. The aim of this study was to perform a cost-effectiveness analysis comparing no therapy to DAAs before TKA. METHODS: A Markov model using input values from the published literature was performed to evaluate the cost-effectiveness of DAA treatment before TKA. Input values included event probabilities, mortality, cost, and health state quality-adjusted life-year (QALY) values for patients who have and do not have HCV. Patients who have HCV were modeled to have an increased rate of periprosthetic joint infection (PJI) infection (9.9 to 0.7%). The incremental cost-effectiveness ratio (ICER) of no therapy versus DAA was compared to a willingness-to-pay threshold of $100,000/QALY. Sensitivity analyses were performed to investigate the effects of uncertainty associated with input variables. RESULTS: Total knee arthroplasty in the setting of no therapy and DAA added 8.1 and 13.5 QALYs at a cost of $25,000 and $114,900. The ICER associated with DAA in comparison to no therapy was $16,800/QALY, below the willingness-to-pay threshold of $100,000/QALY. Sensitivity analyses demonstrated that the ICER was affected by patient age, inflation rate, DAA cost and effectiveness, HCV-associated mortality, and DAA-induced reduction in PJI rate. CONCLUSION: Direct-acting antiviral treatment before TKA reduces risk of PJI and is cost-effective. Strong consideration should be given to treating patients who have HCV before elective TKA. LEVEL OF EVIDENCE: Cost-effectiveness Analysis; Level III.

Risk Stratification in Orthopaedics.

Proper predictive tools are essential to guide patient selection, optimization, category of surgical admission (inpatient, outpatient surgery), and discharge disposition, and predict the risk of readmissions and complications after orthopaedic procedures. Therefore, identification and optimization of patients' perioperative risk for surgery is essential, and understanding these basic concepts is crucial to maximizing patient care quality. It is important to define risk, stratify the existing preoperative attributes, and review key concepts of patient-specific risk calculation and documentation.

Cost Savings Associated With Implementing 4 Total Joint Replacement Electronic Clinical Quality Measures Nationally: 2020-2040.

BACKGROUND: Digital transformation using widely available electronic data is a key component to improving health outcomes and customer choice and decreasing cost and measurement burden. Despite these benefits, existing information on the potential cost savings from electronic clinical quality measures (eCQMs) is limited. METHODS: We assessed the costs of implementing 4 eCQMs related to total hip and/or total knee arthroplasty into electronic health record systems across healthcare systems in the United States. We used published literature and technical expert panel consultation to calculate low-, mid-, and high-range hip and knee arthroplasty surgery projections, and used empirical testing, literature, and technical expert panel consultation to develop an economic model to assess projected cost savings of eCQMs when implemented nationally. RESULTS: Low-, mid-, and high-range projected cost savings for year's 2020, 2030, and 2040 were calculated for 4 orthopedic eCQMs. Mid-range projected cost savings for 2020 ranged from $7.9 to $31.9 million per measure per year. A breakeven of between 0.5% and 5.1% of adverse events (measure dependent) must be averted for cost savings to outweigh implementation costs. CONCLUSIONS: All measures demonstrated potential cost savings. These findings suggest that eCQMs have the potential to lower healthcare costs and improve patient outcomes without adding to physician documentation burden. The Centers for Medicare and Medicaid Services' investment in eCQMs is an opportunity to reduce adverse outcomes and excess costs in orthopedics.

Femoral Head Osteonecrosis: Computed Tomography Not Needed to Identify Collapse When Using the Association Research Circulation Osseous Staging System.

Background: The 2019 Revised Association Research Circulation Osseous (ARCO) Staging Criteria for Osteonecrosis of the Femoral Head (ONFH) only requires plain radiographs and magnetic resonance imaging (MRI) to diagnose and stage ONFH; however, the effectiveness of the 2019 ARCO criteria in the absence of computed tomography (CT) scans has not been investigated. Therefore, the purpose of this study was to evaluate whether CT scanning is a necessary modality for diagnosing/staging ONFH using the ARCO staging system. More specifically, do CT scans help differentiate pre- and post-collapse lesions more than MRI scans? Methods: A study was conducted on 228 ONFH patients diagnosed between January 1, 2008, and December 31, 2018, at a single academic medical center. CT and MRI scans were reviewed by the senior author and other contributors. The ONFH classification was compared between the 2 scans to determine if CT scans were able to further differentiate staging of collapsed lesions vs MRI scans. Results: A diagnosis of ONFH was made by MRI first in 57% (129/228) while 21% (48/228) used MRI and CT simultaneously. Only 22% (51/228) of cases were diagnosed by CT scans first. There were no cases where collapse was found by a CT scan that were not diagnosed by standard x-rays and/or MRIs. Conclusions: CT scans are not a useful adjunct for diagnosing or treating ONFH and are not necessary if MRI is ordered when using the Revised ARCO Staging System for ONFH diagnosis.

Is Tomorrow's Health Care Today: A Look at Current Payment Models for the Future?

The promise of controlling spending and improving the quality of care incentivizes health care providers to prioritize value through alternative payment models. Findings regarding improved value and cost savings of the Comprehensive Care for Joint Replacement (CJR) redesign are consistent throughout selected metropolitan hospitals. Before refinement can take place, reporting on baseline financial status is a necessity to ensure the starting point of hospitals before CJR takes effect. Evidence-based protocols, outcomes-based measures to evaluate results, and cooperation across specialties to deliver high quality care will be necessary to insure improved care throughout the episode. This commentary reviews the CJR program and provides recommendations for the near future in order to best serve the needs of patients as we move forward in the bundled payments direction.

Ethical Considerations in Total Joint Arthroplasty.

Hip and knee arthroplasty surgeries have excellent outcomes and notably improve quality of life. However, ethical issues permeate the practice of adult reconstruction, and as economics and technology evolve, these issues have become increasingly important. This article will review the currently published literature on ethical issues including industry influences, implants and instrumentations, surgical innovation, new technology adoptions, and healthcare policy-relevant issues, including patient cost sharing and bundled care programs. In addition, the direct marketing of implants from the manufacturer to the general public may falsely raise patient expectations concerning the long-term clinical outcome and performance of newer devices in the absence of long-term studies. This article will also focus on relevant contemporary ethical issues that do not necessarily have preexisting published literature or guidelines but, nonetheless, are crucial for adult reconstruction surgeons to address. These issues include access to care and challenges with orthopaedic resident and fellow education. Surgeons must understand the ethical issues that can arise in their clinical practice and how those issues affect patients. Clinicians are tasked with making the best-reasoned judgment possible to optimize their patients' outcomes. Still, the ability to standardize treatment while optimizing individual outcomes for unique patients remains a challenge.

Patient-Specific Safe Zones for Acetabular Component Positioning in Total Hip Arthroplasty: Mathematically Accounting for Spinopelvic Biomechanics.

BACKGROUND: Despite a growing understanding of spinopelvic biomechanics in total hip arthroplasty (THA), there is no validated approach for executing patient-specific acetabular component positioning. The purpose of this study was to (1) validate quantitative, patient-specific acetabular "safe zone" component positioning from spinopelvic parameters and (2) characterize differences between quantitative patient-specific acetabular targets and qualitative hip-spine classification targets. METHODS: From 2,457 consecutive primary THA patients, 22 (0.88%) underwent revision for instability. Spinopelvic parameters were measured prior to index THA. Acetabular position was measured following index and revision arthroplasty. Using a mathematical proof, we developed an open-source tool translating a surgeon-selected, preoperative standing acetabular target to a patient-specific safe zone intraoperative acetabular target. Difference between the patient-specific safe zone and the actual component position was compared before and after revision. Hip-spine classification targets were compared to patient-specific safe zone targets. RESULTS: Of the 22 who underwent revision, none dislocated at follow-up (4.6 [range, 1 to 6.9]). Patient-specific safe zone targets differed from prerevision acetabular component position by 9.1 ± 4.2° inclination/13.3 ± 6.7° version; after revision, the mean difference was 3.2 ± 3.0° inclination/5.3 ± 2.7° version. Differences between patient-specific safe zones and the median and extremes of recommended hip-spine classification targets were 2.2 ± 1.9° inclination/5.6 ± 3.7° version and 3.0 ± 2.3° inclination/7.9 ± 3.5° version, respectively. CONCLUSION: A mathematically derived, patient-specific approach accommodating spinopelvic biomechanics for acetabular component positioning was validated by approximating revised, now-stable hips within 5° version and 3° inclination. These patient-specific safe zones augment the hip-spine classification with prescriptive quantitative targets for nuanced preoperative planning.

A Total Knee Arthroplasty Preoperative Optimization Program Managed by an Advanced Practice Provider (Physician Assistant) Decreases Complications and Cost: A Pilot Study.

BACKGROUND: Studies have shown that optimizing modifiable risk factors leads to improved outcomes, with decreased lengths of stay (LOS), readmissions, complications, and hospital costs. Our goal was to demonstrate that use of an advanced practice provider, physician assistant (PA), within an orthopaedic practice would support these outcomes. METHODS: A preoperative optimization program managed by a PA was instituted at an academic medical center. From November 2019 to December 2022, a pilot group of fifteen (15) consecutive primary total knee arthroplasty (TKA) patients who were successfully optimized with the PA-managed program prior to TKA were matched 2:1 to a cohort of thirty (30) TKA patients who did not undergo optimization. Demographics and the modified readmission risk assessment tool score were used to match patients. Variables evaluated included LOS, emergency department visits, and hospital readmissions within 30 and 90 days after surgery, complications, and hospital costs of care. RESULTS: Optimized patients had less complications (P = .004) and significantly shorter (P < .001) mean LOS (1.27 days vs 2.97 days) compared to nonoptimized patients. The difference of hospital cost between cohorts for the primary admission was significant (P = .049). When readmission costs were included, the average hospital cost for the nonoptimized group was significantly higher than the optimized group (P = .018). CONCLUSIONS: Preoperative optimization led by a PA demonstrated significant reductions in LOS and the costs of care between optimized and non-optimized patients, along with decreased complications.

Treating Hepatitis C Prior to Total Hip Arthroplasty is Cost-effective: A Markov Analysis.

BACKGROUND: Patients infected with the hepatitis C virus (HCV) have high complication rates following total hip arthroplasty (THA). Advances in HCV therapy now enable clinicians to eradicate the disease; however, its cost-effectiveness from an orthopaedic perspective remains to be demonstrated. We sought to conduct a cost-effectiveness analysis comparing no therapy to direct-acting antiviral (DAA) therapy prior to THA among HCV-positive patients. METHODS: A Markov model was utilized to evaluate the cost-effectiveness of treating HCV with DAA prior to THA. The model was powered with event probabilities, mortality, cost, and quality-adjusted life year (QALY) values for patients with and without HCV that were obtained from the published literature. This included treatment costs, successes of HCV eradication, incidences of superficial or periprosthetic joint infection (PJI), probabilities of utilizing various PJI treatment modalities, PJI treatment success/failures, and mortality rates. The incremental cost-effectiveness ratio was compared to a willingness-to-pay threshold of $50,000/QALY. RESULTS: Our Markov model indicates that in comparison to no therapy, DAA prior to THA is cost-effective for HCV-positive patients. THA in the setting of no therapy and DAA added 8.06 and 14.39 QALYs at a mean cost of $28,800 and $115,800. The incremental cost-effectiveness ratio associated with HCV DAA in comparison to no therapy was $13,800/QALY, below the willingness-to-pay threshold of $50,000/QALY. CONCLUSION: Hepatitis C treatment with DAA prior to THA is cost-effective at all current drug list prices. Given these findings, strong consideration should be given to treating patients for HCV prior to elective THA. LEVEL OF EVIDENCE: Cost-effectiveness Analysis; Level III.

Artificial Intelligence for Automated Implant Identification in Total Hip Arthroplasty: A Multicenter External Validation Study Exceeding Two Million Plain Radiographs.

BACKGROUND: The surgical management of complications after total hip arthroplasty (THA) necessitates accurate identification of the femoral implant manufacturer and model. Automated image processing using deep learning has been previously developed and internally validated; however, external validation is necessary prior to responsible application of artificial intelligence (AI)-based technologies. METHODS: We trained, validated, and externally tested a deep learning system to classify femoral-sided THA implants as one of the 8 models from 2 manufacturers derived from 2,954 original, deidentified, retrospectively collected anteroposterior plain radiographs across 3 academic referral centers and 13 surgeons. From these radiographs, 2,117 were used for training, 249 for validation, and 588 for external testing. Augmentation was applied to the training set (n = 2,117,000) to increase model robustness. Performance was evaluated by area under the receiver operating characteristic curve, sensitivity, specificity, and accuracy. Implant identification processing speed was calculated. RESULTS: The training and testing sets were drawn from statistically different populations of implants (P < .001). After 1,000 training epochs by the deep learning system, the system discriminated 8 implant models with a mean area under the receiver operating characteristic curve of 0.991, accuracy of 97.9%, sensitivity of 88.6%, and specificity of 98.9% in the external testing dataset of 588 anteroposterior radiographs. The software classified implants at a mean speed of 0.02 seconds per image. CONCLUSION: An AI-based software demonstrated excellent internal and external validation. Although continued surveillance is necessary with implant library expansion, this software represents responsible and meaningful clinical application of AI with immediate potential to globally scale and assist in preoperative planning prior to revision THA.

A Digital Platform for the Self-Management of Knee Arthritis: MyArthritisRx.com.

MyArthritisRx.com (MARx) is an online digital platform with resources to effectively manage osteoarthritis and directs patients to the appropriate information and tools to manage their disease. The key to self-management is a self-evaluation and staging program powered by an algorithm based on 150,000 arthritis patients. Outcome data (PROMs), comorbidities, demographics, and personalized characteristics are used to provide a personalized self-evaluation and staging assessment which characterizes disease severity and risk of progression. The initial 6-week program was completed by 100 pilot patients with 92% reporting some improvement. MARx offers evidence of efficacy with promise of cost savings and improved arthritis care.

The Role of Stability and Alignment in Improving Patient Outcomes After Total Knee Arthroplasty.

¼: Total knee arthroplasty (TKA) is an effective treatment option for many patients, but a small group of patients are dissatisfied following TKA. ¼: Alignment, in combination with balance, stability, and knee kinematics, is an important modifiable surgical factor that can affect patient outcomes. ¼: Driven by the subset of dissatisfied patients after TKA, new techniques have evolved in the search for a more anatomic reconstruction of individual knee morphology and a more accurate approximation of the individual lower-extremity alignment. ¼: There is a need to optimize 3 aspects of TKA to improve patient outcomes-mechanical tooling processes, implants that resurface the epiphysis, and techniques that respect the variable anatomy of patients.

The COVID-19 Pandemic and Centers of Medicaid and Medicare Services Regulatory Reform Impact on Total Hip Arthroplasty Metrics.

BACKGROUND: Shifts in demand, capacity, and site of service have impacted total hip arthroplasty (THA) volumes and revenues over the 2019-2021 time period. Moving THA off the inpatient-only (IPO) list and the COVID-19 pandemic has caused a shift in delivery away from inpatient services and a decrease in demand. METHODS: Medicare claims data were surveyed for the latest period available (April 1, 2020 to September 2020) and compared with a similar period in 2019 prior to THA removal from the IPO list and before the COVID-19 pandemic. Length of stay (LOS), admission status, site of service, discharge status, cost to CMS (Centers of Medicaid and Medicare Services), and racial disparities were analyzed. RESULTS: From 2019 to 2020, changes in primary THA metrics occurred (overall change in total joint arthroplasty [THA plus total knee arthroplasty metrics]): CMS THA volume decreased from 78,691 to 65,360, -16% (-22%); THA performed as an outpatient increased from 0% to 51% (141%); THA performed as same-day discharge increased from 3% to 12%, 325% (221%); overall LOS decreased from 1.91 to 1.46, -23% (-11%); inpatient LOS increased from 1.92 to 2.05, 7% (16%); outpatient LOS increased from 0.92 to 0.93, 1% (-12%); discharge home increased from 82% to 91%, 12.8% (11%); and CMS spending decreased from $1,033 million to $751 million, -27% (-27%). CONCLUSION: Medicare payments, LOS, discharge to facilities, and volume declined from 2019 to 2020 and were accelerated by IPO list changes and COVID-19 issues. Same-day discharge and hospital outpatient department cases also increased. THA metrics were not affected by race.

Worsening Arthroplasty Utilization With Widening Racial Variance During the COVID-19 Pandemic.

BACKGROUND: Elective arthroplasty surgery in the United States came to a near-complete halt in the spring of 2019 as a response to the COVID-19 pandemic. Racial disparity has been a long-term concern in healthcare with increased focus during the pandemic. The purpose of this study is to evaluate the effects of COVID-19 and race on arthroplasty utilization trends during the pandemic. METHODS: We used 2019 and 2020 Center for Medicare and Medicaid Service fee-for-service claims data to compare arthroplasty volumes prior to and during the COVID-19 pandemic. We compared overall arthroplasty utilization rates between 2019 and 2020 and then sought to determine the effect of race and COVID-19, both independently and combined. RESULTS: There was a decrease in primary total knee arthroplasty (-28%), primary total hip arthroplasty (-14%), primary total hip arthroplasty for fracture (-2%), and revision arthroplasty (-14%) utilization between 2019 and 2020. The highest decrease in overall arthroplasty utilization was in the Hispanic population (34% decrease vs 19% decrease in the White population). We found that a non-White patient was 39.9% (P < .001) less likely to receive a total joint arthroplasty prior to COVID-19. The COVID-19 pandemic further exacerbated the pre-existing racial differences in arthroplasty utilization by decreasing the probability of receiving a total joint arthroplasty for non-White patient by another 12.9% (P < .001). CONCLUSION: We found an overall decreased utilization rate of arthroplasty during the COVID-19 pandemic with further decrease noted in all non-White populations. This raises significant concern for worsening racial disparity in arthroplasty caused by the ongoing pandemic.

Randomised comparative effectiveness trial of Pulmonary Embolism Prevention after hiP and kneE Replacement (PEPPER): the PEPPER trial protocol.

INTRODUCTION: More than 1 million elective total hip and knee replacements are performed annually in the USA with 2% risk of clinical pulmonary embolism (PE), 0.1%-0.5% fatal PE, and over 1000 deaths. Antithrombotic prophylaxis is standard of care but evidence is limited and conflicting. We will compare effectiveness of three commonly used chemoprophylaxis agents to prevent all-cause mortality (ACM) and clinical venous thromboembolism (VTE) while avoiding bleeding complications. METHODS AND ANALYSIS: Pulmonary Embolism Prevention after HiP and KneE Replacement is a large randomised pragmatic comparative effectiveness trial with non-inferiority design and target enrolment of 20 000 patients comparing aspirin (81 mg two times a day), low-intensity warfarin (INR (International Normalized Ratio) target 1.7-2.2) and rivaroxaban (10 mg/day). The primary effectiveness outcome is aggregate of VTE and ACM, primary safety outcome is clinical bleeding complications, and patient-reported outcomes are determined at 1, 3 and 6 months. Primary data analysis is per protocol, as preferred for non-inferiority trials, with secondary analyses adherent to intention-to-treat principles. All non-fatal outcomes are captured from patient and clinical reports with independent blinded adjudication. Study design and oversight are by a multidisciplinary stakeholder team including a 10-patient advisory board. ETHICS AND DISSEMINATION: The Institutional Review Board of the Medical University of South Carolina provides central regulatory oversight. Patients aged 21 or older undergoing primary or revision hip or knee replacement are block randomised by site and procedure; those on chronic anticoagulation are excluded. Recruitment commenced at 30 North American centres in December 2016. Enrolment currently exceeds 13 500 patients, representing 33% of those eligible at participating sites, and is projected to conclude in July 2024; COVID-19 may force an extension. Results will inform antithrombotic choice by patients and other stakeholders for various risk cohorts, and will be disseminated through academic publications, meeting presentations and communications to advocacy groups and patient participants. TRIAL REGISTRATION: NCT02810704.