Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Narcotic Use and Prescribing Trends Among Workers Compensation Patients Undergoing Foot and Ankle Surgery

Category: Midfoot/Forefoot; Hindfoot Introduction/Purpose: Previous studies have shown that workers compensation patients (WC) have worse outcomes, and higher complications rates after orthopaedic surgery. Despite orthopaedic surgeons being the third highest prescribers of narcotic pain medication in the United States there have been no studies to specifically evaluate narcotic use among the WC population. The purpose of this study was to investigate narcotic use among WC patients who underwent foot or ankle operative procedures compared with a procedure matched control group. Methods: A retrospective review was conducted for WC and non-WC patients ages 18 to 70 years old who underwent foot (CPT 28001-28899) or ankle (CPT 27600-27899) procedures in an orthopaedic surgery practice from October 2017 through January 2020. Data collection included demographics, social, surgical, perioperative follow-up and complications. Outcomes measures were timing and number of narcotic prescriptions, total morphine milligram equivalents (MME), and procedure type. Data analysis was performed with SPSS version 28. Comparisons were conducted with Mann-Whitney U test, chi square test, or Fisher’s exact test. Power analysis determined sample size with a 0.05 alpha level, 0.80 power, and 0.5 effect size. Results: 142 total patients met inclusion criteria, with 71 WC patients and 71 non-WC patients. There were no differences regarding the type of foot or ankle procedure performed (p=0.598). WC patients had double the number of overall narcotic prescriptions (median 2 vs 1; p < 0.001). WC patients were prescribed in total 1,125 oxycodone MME and 871.8 hydrocodone MME (P < 0.001), versus 750 oxycodone MME and 450 hydrocodone MME among the non-WC group (p < .008). There was no difference in the number of tramadol prescriptions (p = 0.571). WC patients experienced more days between the date of last narcotic prescription and both index surgery date (median 27 vs 1, p = 0.001) and initial clinic visit date (median 105 vs 49, p = 0.002). Conclusion: This data demonstrates that WC patients portend worse outcomes and utilize narcotics at twice the rate and for longer periods of time post-operatively than non-WC patients. Increased narcotic use may potentiate narcotic dependence and likely leads to worse outcomes. Treating physicians must be aware of these trends in order to best manage these patients. Physicians may need to have longer discussions with WC patients regarding narcotic use post operatively as well as about outcomes and goals of surgery. Physicians should set early expectations with WC patients and clear limits on the amount of narcotics they are willing to prescribe postoperatively

The Workers Compensation Burden: Does Compensation Status Lead to Increased Utilization of Healthcare Resources Following Foot and Ankle Surgery?

Category: Other Introduction/Purpose: The association between workers’ compensation (WC) patients and the increased risk of complications and poor outcomes following orthopaedic procedures has been well documented. Recent studies have shown that WC patients have a higher rate of subsequent pain or injury than non-WC patients following common foot and ankle procedures. Due to the increased risks of complications, poor outcomes, and chronic pain amongst WC patients following orthopaedic procedures, it is possible that these patients consume more healthcare resources than non-WC patients during the post-surgical period. This study aimed to investigate the amount of healthcare resources utilized by WC patients following a foot or ankle procedure compared with a procedure-matched control group. Methods: A retrospective review was conducted of all WC and non-WC patients who had undergone foot (CPT 28001-28899) or ankle (CPT 27600-27899) procedures by a single surgeon from October 2017 through January 2020. Patients were excluded based on age ( 70), bilateral procedures, presence of neuropathy, disability, and insufficient follow-up. Data collection included demographic, social, surgical, perioperative follow-up, and complications. Measures of healthcare burden included patient communications, physical encounters, processed documents, overall total prescriptions, the total number of office visits, days to return to work, and days to discharge from the clinic. Data analysis was performed with SPSS version 28. Comparisons were conducted with Mann-Whitney U test, chi-square test, or Fisher’s exact test. Power analysis determined the sample size with a 0.05 alpha level, 0.80 power, and 0.5 effect size. Results: 142 patients met the inclusion criteria including 71 WC patients and 71 non-WC patients. Measures of healthcare burden were greater in WC patients. WC patients had more communication encounters (median 6 vs 3; P<.001), processed documents (median 6 vs 1; P<.001), total prescriptions (median 5 vs 3; P<.001), the total number of office visits (median 8 vs 6; P<.001), days to return to work (median 119 vs 74; P<.001), and days to discharge (median 267 vs 194; P<.001). WC patients were also more likely to have postoperative complications (OR 2.1; P=.045), secondary surgeries (OR 8.2; P<.001), and new complaints during follow-up (OR 1.9; P=.070). WC was less likely to cancel appointments (OR 0.4; P=.028). Conclusion: WC patients demonstrate increased healthcare resource utilization compared to the non-WC population. WC was associated with a higher burden on office staff requiring more time commitment to a single patient. Double the effort was evident on some measured parameters. WC patients also receive more medication prescriptions overall and are more likely to have complications, subsequent surgery, and new complaints remote to the inciting injury

Economic burden of the Surgical Treatment of Adult Acquired Flatfoot in the US Population

Category: Ankle, Midfoot/Forefoot, Population Health Introduction/Purpose: Numerous studies have been published on the treatment of adult acquired flatfoot deformity (AAFF). However, there has been little focus on it’s incidence, and economic burden in the general US population. This study updates and examines surgical incidence rates, demographic factors, and economic burden compared to our previous study that used data from South Carolina. Our previous study reported on data from 2004-2014 while this study reports on data from 2004-2014 using a nationwide database. Additionally, we evaluated the number and type(s) of surgeries performed for patients with a diagnosis of flatfoot who underwent surgery. Our hypothesis was that the surgical incidence of AAFF and its economic burden would increase given the aging population and improvements in surgical treatment options. Methods: The Nationwide Inpatient Sample (NIS) compiles patient data representing a 20% stratified sample of all hospital discharges nationwide. Along with demographics, diagnosis and procedural codes the NIS includes: admission type, length of stay, age, gender, race, Diagnostic Related Group, discharge status, primary expected payer, total charges, and physician specialty code. Bivariate descriptive statistics were utilized to analyze the data. Surgical incidence was calculated by assessing the number of surgical procedures compared to the number of lives covered by the Centers for Medicare and Medicaid Services (CMS). Demographics and medical comorbidities of patients who progressed to surgical treatment for AAFF were analyzed. The cost associated with the surgical care episode was calculated to determine the economic burden of the disease. Given the retrospective nature of the study, we utilized a regression analysis with multiple dependent variables to look for trends that could be analyzed in a larger cohort or prospective fashion. Results: In total, 160,795 patients underwent AAFF corrective surgery between 2004 and 2014. Patients who underwent surgery for AAFF were more likely to be white, female and in their 5th decade of life. Average surgical incidence during this time period was 5.12%. Patients were most likely to undergo a combination of soft tissue and fusion procedures, followed by soft tissue procedures alone and then fusion procedures in isolation. The total nationwide healthcare costs associated with patients who underwent surgery for AAFF exceeded 4 billion dollars. Conclusion: Our data demonstrates that there has been an increasing burden of disease for AAFF on society over the past 10 years. Patients undergoing surgery for AAFF contributed more than 4 billion dollars to national healthcare costs between 1994- 2014. Our study confirmed prior small scale studies of the population most at risk and demonstrated an increasing surgical incidence. The increase in incidence and burden parallel rising rates of diabetes and obesity seen nationwide, known risk factors for AAFF. We hope that this data will lead to increased patient education, clinical awareness and resource allocation for future study of AAFF disease prevention