Faculty Bibliography

BACKGROUND & AIMS/OBJECTIVE:Renal disease is a risk factor for peripheral artery disease (PAD), yet its impact on outcomes after lower extremity (LE) revascularization is not well established. We aimed to characterize the association between chronic kidney disease (CKD) and/or end stage renal disease (ESRD) and post-procedural outcomes in PAD patients undergoing LE revascularization in the United States. METHODS:Adults age ≥18 years undergoing surgical or endovascular LE revascularization for PAD with and without CKD or ESRD were identified from the 2014 Nationwide Readmissions Database. Major adverse cardiovascular events (MACE), defined as a composite of death, myocardial infarction or ischemic stroke, were identified for patients with and without renal disease. All-cause hospital readmissions within 6 months of discharge were determined for all survivors. RESULTS:Among 39,441 patients with PAD hospitalized for LE revascularization, 10,530 had renal disease (26.7%), of whom 69% had CKD without ESRD and 31% had ESRD. Patients with renal disease were more likely to have MACE after LE revascularization (5.2% vs. 2.5%; adjusted OR [aOR] 1.74, 95% CI 1.40-2.16), require LE amputation (26.1% vs. 12.2%; aOR 1.33, 95% CI 1.19-1.50), and require hospital readmission within 6 months (61.0% vs. 43.6%; adjusted HR [aHR] 1.38, 95% CI 1.28-1.48) compared to those without renal disease. CONCLUSIONS:Renal disease is common among patients undergoing LE revascularization for PAD and was independently associated with in-hospital MACE, LE amputation, and hospital readmission within 6 months. Additional efforts to improve outcomes of patients with renal disease and PAD requiring LE revascularization are necessary.

Background/UNASSIGNED:Critical limb ischemia (CLI) is a severe stage of peripheral arterial disease and has a substantial disease and economic burden not only to patients and families, but also to the society and healthcare systems. We aim to develop a personalized prediction model that utilizes baseline patient characteristics prior to CLI diagnosis to predict subsequent 1-year all-cause hospitalizations and total annual healthcare cost, using a novel Bayesian machine learning platform, Reverse Engineering Forward Simulation™ (REFS™), to support a paradigm shift from reactive healthcare to Predictive Preventive and Personalized Medicine (PPPM)-driven healthcare. Methods/UNASSIGNED:Patients ≥ 50 years with CLI plus clinical activity for a 6-month pre-index and a 12-month post-index period or death during the post-index period were included in this retrospective cohort of the linked Optum-Humedica databases. REFS™ built an ensemble of 256 predictive models to identify predictors of all-cause hospitalizations and total annual all-cause healthcare costs during the 12-month post-index interval. Results/UNASSIGNED:The mean age of 3189 eligible patients was 71.9 years. The most common CLI-related comorbidities were hypertension (79.5%), dyslipidemia (61.4%), coronary atherosclerosis and other heart disease (42.3%), and type 2 diabetes (39.2%). Post-index CLI-related healthcare utilization included inpatient services (14.6%) and ≥ 1 outpatient visits (32.1%). Median annual all-cause and CLI-related costs per patient were $30,514 and $2196, respectively. REFS™ identified diagnosis of skin and subcutaneous tissue infections, cellulitis and abscess, use of nonselective beta-blockers, other aftercare, and osteoarthritis as high confidence predictors of all-cause hospitalizations. The leading predictors for total all-cause costs included region of residence and comorbid health conditions including other diseases of kidney and ureters, blindness of vision defects, chronic ulcer of skin, and chronic ulcer of leg or foot. Conclusions/UNASSIGNED:REFS™ identified baseline predictors of subsequent healthcare resource utilization and costs in CLI patients. Machine learning and model-based, data-driven medicine may complement physicians' evidence-based medical services. These findings also support the PPPM framework that a paradigm shift from post-diagnosis disease care to early management of comorbidities and targeted prevention is warranted to deliver a cost-effective medical services and desirable healthcare economy.

BACKGROUND:Patients with peripheral artery disease (PAD) have a higher risk of major adverse cardiovascular events (MACE) compared with those without PAD. OBJECTIVES/OBJECTIVE:The aim of this post hoc analysis was to evaluate sex-specific differences in MACE and limb events in the EUCLID (Examining Use of Ticagrelor in PAD) trial. METHODS:Cox proportional hazards models were used to compare time-to-event outcomes stratified by sex. Covariates were introduced after adjusted model selection. RESULTS:EUCLID enrolled 13,885 patients with PAD (28% women [n = 3,888]). PAD severity and medical treatment were comparable between sexes, whereas prior lower extremity revascularization was reported less frequently in women (54.8% vs. 57.3%; p = 0.006). Women were older (mean ± SD age: 67.8 ± 8.9 vs. 66.1 ± 8.2 years; p < 0.001) and more likely to have diabetes mellitus (p = 0.004), hypertension, hyperlipidemia, and chronic kidney disease (all p < 0.001). Over a mean follow-up of 30 months, women had a lower risk of MACE (9.5% vs. 11.2%; adjusted hazard ratio: 0.77; 95% confidence interval: 0.68 to 0.88; p < 0.001) and all-cause-mortality (7.6% vs. 9.7%; adjusted hazard ratio: 0.61; 95% confidence interval: 0.53 to 0.71; p < 0.001). In contrast, risk for major adverse limb events (2.6% vs. 3.0%) and hospitalization for acute limb ischemia (1.6% vs. 1.7%) were not different by sex. CONCLUSIONS:Although women with PAD are at lower risk for MACE and all-cause mortality, risk for limb events was similar between sexes over a mean follow-up of 30 months. Understanding sex-specific differences and dissociation between baseline cardiovascular risk and subsequent cardiovascular events requires further investigation. (A Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease [EUCLID]; NCT01732822).

In the original article. The third author name is incorrect. The correct name is Nicholas J. Leeper.

INTRODUCTION/BACKGROUND:Collectively, coronary artery disease (CAD) and peripheral artery disease (PAD) are highly prevalent and are associated with increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Improved ability to identify those at highest risk of these events may help optimize secondary prevention efforts in this population. METHODS:Using the Optum Integrated Database, a healthcare claims database linked to electronic medical records (EMR), we identified patients with CAD and/or PAD between January 1, 2009, and September 30, 2016. Index date was the earliest date on which chronic and stable disease was established. Follow-up ran from index date until earliest of patient death, plan disenrollment, or end of study. We developed multivariate Cox proportional hazards models to identify predictors of MACE and/or MALE, limited to measures presumed available to clinicians during patient encounters (e.g., age, presence of selected comorbidities). RESULTS: = 0.98), ranging from 2.3 per 100 PYs among those without predictors (4.9% of patients) to 18.7 per 100 PYs among those with ≥ 6 (6.9%). Patients with ≥ 1 predictor experienced 7.4 MACE and/or MALE per 100 PYs. CONCLUSION/CONCLUSIONS:Readily identifiable predictors can be used to identify subgroups with chronic CAD and/or PAD at elevated risk of MACE and/or MALE. Further research is required to understand the degree to which these subgroups may benefit from early identification and treatment with secondary prevention therapies. FUNDING/BACKGROUND:Janssen Pharmaceuticals.

Introduction - Critical limb ischemia (CLI) implies a heightened risk for cardiovascular morbidity and mortality. Methods - The EUCLID trial (NCT01732822) investigated the effect of antithrombotic monotherapy, ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily, in patients with symptomatic peripheral arterial disease (PAD). Inclusion criteria were previous lower extremity revascularization (LER) or ankle-brachial index (ABI) <=0.80, randomizing 13,885 patients. Ticagrelor was not superior to clopidogrel in the reduction of cardiovascular events, nor did major bleeding differ between groups. The present study focuses on patients with CLI at baseline, defined by rest pain, minor or major tissue loss. Results - At baseline 643 patients (4.6 %) had CLI (Rutherford 4 (58.8%), Rutherford 5-6 (41.2%)). The proportion of patients with CLI in the LER group (351/7873, 4.5%) or low ABI group (292/6009, 4.9%) was similar.Diabetes mellitus was more common in the CLI group (49.3% vs 38.0%, p<0.0001), while a history of coronary artery disease was more common for the non-CLI group (29.2% vs 25.3%, p=0.035). A history of carotid disease was more frequent in non-CLI patients (18.0% vs 12.1%, p=0.0002) and a corresponding relationship was recorded for hypertension (non-CLI 78.4%, CLI 74.2%, p=0.01). Before randomization, more CLI than non-CLI patients were on clopidogrel (40.0% vs 31.8%, p<0.0001) whereas aspirin treatment was more common in the non-CLI group (67.3% vs 55.5%, p<0.0001). Dual antiplatelet therapy (aspirin and clopidogrel) was used by 16.2 % of CLI patients and 16.3 % of the non-CLI group. Statins were used by 73.8% of non-CLI patients, and 64.1% of the CLI group (p<0.0001). A history of major amputation was more common in patients with CLI (10.3%) compared to non-CLI patients (2.1%), p<0.0001. The primary efficacy endpoint, cardiovascular death, MI or ischemic stroke occurred significantly more frequently among CLI patients with a rate of 8.85 versus 4.28 per 100 patient-years (HR 2.07(1.72-2.48), p<0.0001; Fig), and this difference remained significant after adjustment for baseline characteristics (HR 1.43(1.16-1.76), p=0.0009). When including acute limb ischemia requiring hospitalization with MACE, significant differences remained, also after adjustment for baseline characteristics (HR 1.38(1.13-1.69), p=0.0016). LER was more common in CLI compared with non-CLI patients (HR 1.29(1.05-1.59), p=0.018), the difference not remaining significant after adjustment (HR 1.19(0.96-1.49), p=0.12). Bleeding did not differ between patients with and without CLI.The primary efficacy endpoint did not differ between ticagrelor and clopidogrel treated patients in the respective CLI and non-CLI groups, nor did bleeding. [Formula presented] Conclusion - Patients suffering CLI represented nearly 5% of patients enrolled in the EUCLID trial. The low amputation rate at baseline suggests milder forms of CLI dominated. CLI patients had a 2-fold higher rate of cardiovascular mortality and morbidity compared to non-CLI patients. Further efforts are required to reduce the risk for cardiovascular events in PAD, especially in patients with CLI.
Copyright