LW and OB are employees of STATinMED Research, which is a paid consultant to Janssen Scientific Affairs. PW receives speaker fees from Bayer Healthcare and Daiichi Sankyo, writing committee fees from Itreas, and grant support fees from Pfizer/BMS [ORCID number 000-0002-8657-8326]. FP has received grants from Abbott, Alere, Banyan, Cardiorentis, Janssen, Portola, Pfizer, Roche, and ZS Pharma; is a consultant to Alere, Beckman, Bo Boehringer-Ingelheim, Cardiorentis, Instrument Labs, Janssen, Phillips, Portola, Prevencio, Singulex, The Medicine's Company, and ZS Pharma; and also has ownership interests at the Comprehensive Research Associate LLC, Emergencies in Medicine LLC. CIC has received grant funding and consulting fees from Janssen Scientific Affairs, LLC, Raritan, NJ and Bayer Pharma AG, Berlin, Germany. GF has received research support from Novartis, Siemens, Pfizer, Portola, and PCORI; has advised Janssen Scientific Affairs, LLC; and receives speaker fees from Janssen. JS and CC and are employees of Janssen Scientific Affairs. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Clinical guidelines recommend early discharge of patients with low-risk pulmonary embolism (LRPE). This study measured the overall impact of early discharge of LRPE patients on clinical outcomes and costs in the Veterans Health Administration population. Adult patients with ≥1 inpatient diagnosis for pulmonary embolism (PE) (index date) between 10/2011-06/2015, continuous enrollment for ≥12 months pre- and 3 months post-index date were included. PE risk stratification was performed using the simplified Pulmonary Embolism Stratification Index. Propensity score matching (PSM) was used to compare 90-day adverse PE events (APEs) [recurrent venous thromboembolism, major bleed and death], hospital-acquired complications (HACs), healthcare utilization, and costs among short (≤2 days) versus long length of stay (LOS). Net clinical benefit was defined as 1 minus the combined rate of APE and HAC. Among 6,746 PE patients, 95.4% were men, 22.0% were African American, and 1,918 had LRPE. Among LRPE patients, only 688 had a short LOS. After 1:1 PSM, there were no differences in APE, but short LOS had fewer HAC (1.5% vs 13.3%, 95% CI: 3.77–19.94) and bacterial pneumonias (5.9% vs 11.7%, 95% CI: 1.24–3.23), resulting in better net clinical benefit (86.9% vs 78.3%, 95% CI: 0.84–0.96). Among long LOS patients, HACs (52) exceeded APEs (14 recurrent DVT, 5 bleeds). Short LOS incurred lower inpatient ($2,164 vs $5,100, 95% CI: $646.8-$5225.0) and total costs ($9,056 vs $12,544, 95% CI: $636.6-$6337.7). LRPE patients with short LOS had better net clinical outcomes at lower costs than matched LRPE patients with long LOS.
Pulmonary embolism (PE) is responsible for at least 100,000–200,000 deaths in the United States each year, and is the third major cause of cardiovascular death after myocardial infarction and cerebrovascular accidents [
PE is generally diagnosed in patients by performing a Computed Tomography Angiography (CTA), and the majority of US patients are admitted for risk stratification and initiation of anticoagulation therapy [
PE is associated with a substantial burden of health care utilization and associated costs. The annual cost per patient for an initial episode of PE ranges from $13,000 –$31,300, and with recurrent episodes, the annual cost per patient is $11,014 –$14,722 [
Given the numerous studies supporting the benefit of early discharge among LRPE patients, the purpose of our study was to examine whether short length of stay (LOS) is associated with improved clinical and economic outcomes in a real-world setting.
This was a longitudinal, retrospective cohort study assessing the Veterans Health Administration (VHA) population from October 1, 2010 through September 30, 2015. The VHA is the largest integrated health care system in the United States, providing care at 1,245 health care facilities, including 170 VA medical centers and 1,065 outpatient clinics, serving more than 9 million enrolled veterans across the country [
Electronic health data collected within the VHA national Medical SAS® Dataset and Decision Support System were evaluated, using the medical, pharmacy, laboratory, and VHA health plan enrollment information [
Patients were included in the study if they were ≥18 years of age, had ≥1 inpatient diagnosis for PE (ICD-9-CM codes: 415.1, 415.11, 415.19), had a prescription claim for an anticoagulant (unfractionated heparin, low-molecular-weight heparin [LMWH], warfarin, or novel oral anticoagulants [NOACs]) during the hospital stay and were continuously enrolled in a health plan with medical and pharmacy benefits for at least 12 months prior to the index hospitalization discharge, including the hospital stay (baseline period) until 3 months post-index date or death (follow-up period), whichever came first. The first PE diagnosis date was designated as the initial diagnosis date, and the discharge date was designated as the index date. Patients who were administered subcutaneous heparin during the hospital stay were not included, since many patients are given subcutaneous heparin as a prophylaxis for deep vein thrombosis and PE. Also, patients with a PE claim or any anticoagulant claim prior to the initial diagnosis date were excluded.
Eligible PE patients were stratified using the sPESI criteria into low-risk PE (LRPE) and high-risk PE (HRPE). The sPESI is a simplified version of the PESI in which selected variables of the original score are included (age, history of cancer, history of chronic cardiopulmonary disease, pulse, systemic blood pressure, and oxygen saturation levels). Patients scoring 0 points were considered at low risk. LRPE patients were further stratified, based on their LOS, into short LOS (≤2 days) and long LOS (>2 days) cohorts.
Patient demographics, including age, gender, race, and body mass index (BMI), during the baseline period were assessed. In addition, clinical characteristics, including Charlson comorbidity index (CCI) score, individual comorbidities (hospitalized DVT [ICD-9-CM codes 451.1, 453], left ventricular [LV] dysfunction [ICD-9-CM code 429.9], cardiac dysrhythmia [ICD-9-CM codes 427.0–427.9]) and administration of various diagnostic tests were recorded. Also, patients with various clinical markers including troponin I/T and natriuretic peptide testing results during the index hospitalization were assessed.
The percentage of patients with HACs and surgical procedures (thrombolysis, placement of inferior vena cava filter) during index hospitalization were evaluated. HACs were identified using the ICD-9-CM codes (
Descriptive statistics were provided for all study variables, including baseline demographics, clinical characteristics, and outcome variables among short LOS and long LOS LRPE cohorts, and statistical tests of significance (chi-square for categorical variables, t-test for continuous variables) were conducted to assess differences between the cohorts. Logistic regression was used to identify the predictors of hospital LOS (short vs long LOS) among LRPE patients. Patient characteristics such as gender, race, BMI, CCI score, baseline comorbidities, clinical markers, and diagnostic tests were included as independent variables in the model. Hospital LOS was the dependent variable. Odds ratio (OR) and 95% confidence intervals (CIs) were presented. Propensity score matching (PSM) was used to compare the clinical and economic outcomes among short vs long LOS LRPE cohorts. Each short LOS patient was matched to a long LOS patient within 0.01 units of the propensity score. The propensity score was calculated via a logistic regression model. The adequacy of the matching procedure was assessed by standardized difference; a difference of <10% is considered well balanced. Costs were compared between the PSM-matched cohorts with a generalized linear model with a gamma distribution and log link to account for the expected non-normality of cost data. All analyses were conducted using SAS statistical software (SAS 9.3, Copyright 2012, SAS Institute Inc., Cary, NC, USA.)
After applying the inclusion and exclusion criteria, 6,746 PE patients were included in the study. Among these patients, 1,918 (28.4%) met the definition of being LRPE patients. Among the LRPE patients, 688 (35.9%) had a short LOS and 1,230 (64.1%) had a long LOS (
HRPE: high risk pulmonary embolism; LOS: length of stay; LRPE: low-risk pulmonary embolism.
Before matching, LRPE patients with a long LOS were older (60.7 vs 58.4 years, 95% CI: 1.28–3.37) and a higher percentage were men (94.6 vs 91.3, 95% CI: 1.01–1.06) as compared to LRPE patients with a short LOS. Long LOS patients had higher CCI scores (1.1 vs 0.8, 95% CI: 0.16–0.42) and a higher proportion of patients with individual baseline comorbidities, including moderate or severe renal disease (20.3% vs 14.2%, 95% CI: 1.04–1.96), diabetes (29.3% vs 22.5%, 95% CI: 1.10–1.53), and cardiac dysrhythmia (16.4% vs 10.0%, 95% CI: 1.27–2.12) as compared to short LOS patients. Also, the long LOS cohort had a higher proportion of patients with troponin I testing (38.1% vs. 30.1%, 95% CI: 1.11–1.45) and elevated troponin I >0.04 ng/ml (46.5% vs 23.7%, 95% CI: 1.11–1.45) or troponin T >0.03 ng/ml (73.7% vs 28.6%, 95% CI: 1.08–6.16) during index hospitalization as compared to the short LOS cohort (
Long LOS | Short LOS |
95% Wald Confidence Limits | ||||
---|---|---|---|---|---|---|
(>48 hrs) Cohort | ||||||
N = (1,230) | N = (688) | |||||
N/ | %/SD | N/ | %/SD | |||
Mean | Mean | |||||
Mean, SD | 60.7 | 11.1 | 58.4 | 11.2 | 1.28 | 3.37 |
Median | 63 | 61 | ||||
18–45 | 117 | 9.5% | 100 | 14.5% | 0.51 | 0.84 |
46–64 | 608 | 49.4% | 346 | 50.3% | 0.90 | 1.08 |
65+ | 505 | 41.1% | 242 | 35.2% | 1.03 | 1.32 |
Male | 1164 | 94.6% | 628 | 91.3% | 1.01 | 1.06 |
Female | 66 | 5.4% | 60 | 8.7% | 0.44 | 0.86 |
White | 786 | 63.9% | 437 | 63.5% | 0.94 | 1.08 |
Black | 319 | 25.9% | 187 | 27.2% | 0.82 | 1.11 |
Unknown | 94 | 7.6% | 40 | 5.8% | 0.92 | 1.88 |
Other | 31 | 2.5% | 24 | 3.5% | 0.43 | 1.22 |
Body Mass Index (kg/m2) | 31.6 | 10.3 | 31.23 | 6.6 | -0.49 | 1.21 |
Charlson Comorbidity Index Score | 1.1 | 1.5 | 0.8 | 1.3 | 0.16 | 0.42 |
Myocardial Infarction | 67 | 5.5% | 33 | 4.8% | 0.76 | 1.70 |
Congestive heart failure | 0 | 0.0% | 0 | 0.0% | ||
Peripheral vascular disease | 74 | 6.0% | 40 | 5.8% | 0.71 | 1.50 |
Dementia | 15 | 1.2% | 1 | 0.2% | 1.11 | 63.38 |
Cerebrovascular disease | 128 | 10.4% | 45 | 6.5% | 1.15 | 2.21 |
Chronic pulmonary disease | 81 | 6.6% | 49 | 7.1% | 0.66 | 1.30 |
Rheumatologic disease or connective tissue |
21 | 1.7% | 7 | 1.0% | 0.72 | 3.93 |
Peptic Ulcer disease | 29 | 2.4% | 4 | 0.6% | 1.43 | 11.49 |
Mild liver disease | 16 | 1.3% | 8 | 1.2% | 0.48 | 2.60 |
Hemiplegia or paraplegia | 0 | 0.0% | 0 | 0.0% | ||
Moderate or severe renal disease | 250 | 20.3% | 98 | 14.2% | 1.04 | 1.96 |
Diabetes | 360 | 29.3% | 155 | 22.5% | 1.10 | 1.53 |
Any tumor (Other Malignancy) | 18 | 1.5% | 4 | 0.6% | 0.55 | 11.62 |
Moderate or severe liver disease | 24 | 2.0% | 6 | 0.9% | 0.48 | 10.51 |
Metastatic solid tumor | 0 | 0.0% | 0 | 0.0% | ||
Diabetes + complications | 178 | 14.5% | 64 | 9.3% | 1.05 | 2.30 |
AIDS | 90 | 7.3% | 42 | 6.1% | 0.49 | 2.93 |
Cardiac Dysrhythmia | 202 | 16.4% | 69 | 10.0% | 1.27 | 2.12 |
LV dysfunction | 33 | 2.7% | 6 | 0.9% | 1.30 | 7.31 |
Hospitalized DVT | 416 | 33.8% | 208 | 30.2% | 0.97 | 1.28 |
CTA | 453 | 36.8% | 496 | 72.1% | 0.47 | 0.56 |
ECHO | 24 | 2.0% | 13 | 1.9% | 0.53 | 2.01 |
VQ Scan | 23 | 1.9% | 18 | 2.6% | 0.39 | 1.32 |
Venous Doppler Ultrasound | 210 | 17.1% | 172 | 25.0% | 0.57 | 0.82 |
# Patients with Troponin I, N | 469 | 38.1% | 207 | 30.1% | 1.11 | 1.45 |
# Patients with Troponin T, N | 19 | 1.5% | 14 | 2.0% | 0.38 | 1.50 |
# Patients with Natriuretic Peptide testing, N | 453 | 36.8% | 223 | 32.4% | 1.00 | 1.29 |
CTA: Computed Tomography Angiography; DVT: deep vein thrombosis; ECHO: echocardiogram; LOS: length of stay; LRPE: low-risk pulmonary embolism; LV: left ventricular SD: standard deviation; VQ: lung ventilation/perfusion
After 1:1 PSM, a total of 784 (40.8%) patients were included in the long LOS (n = 392) and short LOS (n = 392) LRPE cohorts. The cohorts were well-balanced based on baseline demographic and clinical characteristics with standardized differences of < 10%.
There were no differences in the follow-up adverse PE events, including recurrent VTE, major bleeding, and death between the short LOS and long LOS LRPE cohorts. However, LRPE patients with a short LOS had fewer HACs (1.5% vs 13.3%, 95% CI: 3.77–19.94), including hospital-acquired pneumonia (0.0% vs 8.4%) during index hospitalization. Additionally, the short LOS cohort had a lower proportion of patients with bacterial pneumonia (5.9% vs 11.7%, 95% CI: 1.24–3.23) than the long LOS cohort. Net clinical benefit was higher for short LOS patients. (86.9% vs 78.3%, 95% CI: 0.84–0.96). Among long LOS, the number of HACs (52) exceeded adverse PE events (14 recurrent DVT, 5 bleeds, 10 deaths) (
Long LOS | Short LOS (≤2 days) Cohort | 95% Wald Confidence Limits |
||||
---|---|---|---|---|---|---|
(≥2 days) Cohort | ||||||
N = (392) | N = (392) | |||||
N/Mean | %/SD | N/Mean | %/SD | |||
Hospital-acquired complications, any | 52 | 13.3% | 6 | 1.5% | 3.77 | 19.94 |
Catheter-associated urinary tract Infection | 2 | 0.5% | 0 | 0.0% | ||
Methicillin-resistant staphylococcus aureus | 5 | 1.3% | 1 | 0.3% | 0.59 | 42.60 |
3 | 0.8% | 0 | 0.0% | |||
Hospital-acquired (bacterial) pneumonia | 33 | 8.4% | 0 | 0.0% | ||
Foreign object retained after surgery | 1 | 0.3% | 0 | 0.0% | ||
Pressure ulcer stages III & IV | 1 | 0.3% | 0 | 0.0% | ||
Trauma/injury | 13 | 3.3% | 5 | 1.3% | 0.94 | 7.22 |
Vascular catheter-associated infection | 1 | 0.3% | 0 | 0.0% | ||
Surgical site infection | 1 | 0.3% | 0 | 0.0% | ||
Bacterial pneumonia | 46 | 11.7% | 23 | 5.9% | 1.24 | 3.23 |
Recurrent VTE | 14 | 3.6% | 13 | 3.3% | 0.51 | 2.26 |
Time to first VTE, days | 34.6 | 26.7 | 34 | 18.3 | -17.70 | 18.84 |
Major Bleeding | 5 | 1.3% | 4 | 1.0% | 0.34 | 4.62 |
Time to first Major Bleeding, days | 22.4 | 21.3 | 37 | 29.4 | -54.42 | 25.22 |
Death | 10 | 2.6% | 10 | 2.6% | 0.42 | 2.38 |
Time to Death, days | 30.9 | 23.6 | 40.5 | 24 | -31.99 | 12.79 |
307 | 78.3% | 341 | 86.9% | 0.84 | 0.96 |
* CI cannot be calculated if any one of the cohorts had 0.00% HAC's
PE: pulmonary embolism; PSM: propensity score matching; SD: Standard Deviation; VTE: venous thromboembolism
The long LOS cohort, as compared to the short LOS cohort, had a higher number of pharmacy visits per patient (12.2 vs 9.4, 95% CI: 1.34–4.18) and incurred higher inpatient ($5,100 vs $2,164, 95% CI: $646.80-$5225.00), total medical ($11,135 vs $7,843, 95% CI: $796.40-$5787.70) and total costs ($12,544 vs $9,056, 95% CI: $636.60-$6337.70;
LOS: length of stay.
Patients with CTA (OR: 4.8, 95% CI: 3.8–6.0), VQ scan (OR: 3.8, 95% CI: 1.9–7.7), and venous Doppler ultrasound (OR: 1.4, 95% CI: 1.1–1.9) in the baseline period had increased probability of a short LOS among LRPE patients, and patients with assays for clinical markers troponin I (OR: 0.7, 95% CI: 0.5–0.9) and natriuretic peptide testing (OR: 0.7, 95% CI: 0.6–0.9) during index hospitalization had decreased probability of a short LOS. The odds of a short LOS decreased among LRPE patients with LV dysfunction (OR: 0.2, 95% CI: 0.1–0.6), hospitalized DVT (OR: 0.7, 95% CI: 0.6–0.9), and peptic ulcer disease (OR: 0.3, 95% CI: 0.1–1.0).
The findings from our study should be viewed in the context of some study limitations. First, the study relied on retrospective claims data. While claims data are extremely valuable for the efficient and effective examination of health care outcomes, treatment patterns, and costs, they are collected for payment and not research. The presence of a diagnosis code on medical claims is not a positive presence of disease and may be incorrectly coded or included as rule-out criteria rather than the actual disease. To ensure exclusion of any rule-out PE diagnosis, PE patients were required to have an anticoagulant claim during their hospital stay. The presence of a claim for a filled prescription does not indicate the medication was consumed or taken as prescribed. Also, prescriptions filled over-the-counter or provided as samples by the physician are not observed in claims data. Thus, the true number of medications prescribed may not be accurately recorded. Third, certain clinical and disease-specific parameters are not readily available in claims data that could have effect on study outcomes.
Patients in the long LOS cohort may have had non-coded reasons explaining their longer stay. For example, those with unstable social situations may have been kept longer while attempting to arrange more stable outpatient management strategies. Further, longer LOS patients may have been perceived to suffer greater fragility by their physicians, which may explain their older age. Finally, it should be noted that troponin results are not included in the majority of PE risk stratification scores. Thus, higher troponin levels found in the longer LOS cohort may have prompted additional evaluation that required a longer inpatient time or may have prompted a longer admission as some studies suggest higher risk with elevated biomarkers. Interestingly, our study does not confirm worse outcomes in patients with elevated biomarkers.
Finally, it should also be noted that PSM adjustment cannot resolve problems due to imbalances in unmeasured factors. It is possible that there were unobserved variables that the PSM does not correct for in risk-adjusted tables. The current study also represented only US data from a specific subpopulation (VHA veterans), who were mostly elderly men. Therefore, the general applicability of our findings to young male patients or females requires further study.
PE is one of the leading causes of cardiovascular morbidity and mortality [
In a study conducted by Dentali et al., 26.1% of PE patients were classified as low-risk, while 30.7% were classified as low-risk by Jimenez et al., per the sPESI criteria [
In our analysis, patients with a longer LOS also had higher mean troponin levels. Some PE risk stratification tools include troponin, levels but the data is inconclusive on the risk associated with elevations therefore we included patients with elevations in the LRPE cohort. This is in contradistinction to a study conducted by Kang et al., in high-risk patients who had elevated levels of cardiac biomarkers including troponin T/I [
Our study showed that long LOS patients had more inpatient and pharmacy visits and higher health care costs. Previous studies showed that increased hospital LOS is an important driver of costs among PE patients and suggested that implementation of outpatient treatment strategies or early discharge would substantially reduce health care costs [
Recently-published practice guidelines that recommend outpatient care for carefully selected patients with non-massive PE fail to specify how these low-risk patients can be identified accurately [
In summary, the results of this study showed that LRPE patients with a short LOS had better clinical outcomes at lower costs than those with a long LOS. Therefore, risk stratification of PE patients is of utmost importance, and reducing the LOS among LRPE patients may substantially reduce the disease’s clinical and economic burden.
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Editorial support for this study was provided by Michael Moriarty of STATinMED Research.