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The American Journal of Managed Care June 2012
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Thromboembolism Prophylaxis in Medical Inpatients: Effect on Outcomes and Costs
Onur Baser, MS, PhD; Nishan Sengupta, PhD; Anne Dysinger, MA; and Li Wang, MA, PhD
Automating Care Quality Measurement With Health Information Technology
Brian Hazlehurst, PhD; Mary Ann McBurnie, PhD; Richard A. Mularski, MD, MSHS, MCR; Jon E. Puro, MPA-HA; and Susan L. Chauvie, RN, MPA-HA
Role of Insurance, Income, and Affordability in Human Papillomavirus Vaccination
Nadereh Pourat, PhD; and Jenna M. Jones, MPH
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Sachin H. Jain, MD, MBA; Riya Goyal, BA; Susannah Fox, BA; and William H. Shrank, MD, MS, HS
Quality Care Opportunities: Refining Physician Performance Measurement in Ambulatory Care
Kimberly M. Lovett, MD; and Bryan A. Liang, MD, PhD, JD
Unintended Consequences of a Quality Measure for Acute Bronchitis
Serena Roth, MD; Ralph Gonzales, MD, MSPH; Tammy Harding-Anderer, PhD; Frederick J. Bloom, Jr, MD, MMM; Thomas Graf, MD; Melissa S. Stahl, MPH; Judith H. Maselli, MSPH; and Joshua P. Metlay, MD, PhD
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Qian Cai, MS, MSPH; Hiangkiat Tan, MS, BPharm; and Joseph Singer, MD
Barriers to Transition of Obese Patients From Hospital to Community
Jane Miles, MSN, RN, NEA-BC; Darren P. Anderson, MSN, RN, ACM; Martha Engelke, PhD; Mary K. Kirkpatrick, RN, MSN, EdD; Mary Lisa Pories, MSW; Wanda G. Waters, RN, BSN; Frank R. Watkins, RN, CCRC; Marie E. Pokorny, RN, MSN, PhD; and Mary Ann Rose, MSN, EdD

Thromboembolism Prophylaxis in Medical Inpatients: Effect on Outcomes and Costs

Onur Baser, MS, PhD; Nishan Sengupta, PhD; Anne Dysinger, MA; and Li Wang, MA, PhD
VTE prophylaxis is underutilized in medical patients in US hospitals, but the occurrence of VTE has a major clinical and economic impact.
Objectives: To evaluate the real-world use of venous thromboembolism (VTE) prophylaxis among medical inpatients and the impact of VTE prophylaxis on outcomes and cost.

Study Design: Retrospective analysis of patientlevel administrative claims data for medical inpatients at risk of VTE and linked outpatient data.

Methods: Data were analyzed from patients admitted to the hospital from 2005 to 2007 (calendar years) with a primary diagnosis of chronic heart failure, thromboembolic stroke, severe lung disease, acute infection, or cancer (index hospitalization), according to whether they received VTE prophylaxis or not. The number of VTE events, time to VTE event, length of hospital stay, and number of major or minor bleeding events were analyzed from the index date until the end of follow-up (180 days postdischarge) or death.

Results: Overall, 7127 of 13,293 patients (53.6%) received VTE prophylaxis. Prophylaxis significantly reduced the incidence of VTE compared with no prophylaxis (0.06% vs 3.44%, respectively; P <.00001) and increased the median time to VTE (182 vs 27 days, respectively). Prophylaxis also significantly reduced the incidence of VTE in the 180 days postdischarge. Readmission rates were similar between groups. Major bleeding occurred in 1.57% of patients receiving low molecular weight heparin + warfarin versus <.6% receiving any other form of prophylaxis. The development of VTE or major or minor bleeding events significantly increased total medical costs versus no VTE events (P <.0001) or no bleeding events (P <.0003).

Conclusions: This real-world analysis showed that thromboprophylaxis was underutilized in medical patients, even though the clinical and economic impact of VTE was significant.

(Am J Manag Care. 2012;18(6):294-302)
A retrospective analysis of data from medical inpatients at risk of venous thromboembolism (VTE) (n = 13,293) examined the impact of VTE prophylaxis during admission on clinical outcomes and costs:

  • During the index hospitalization, 53.6% received VTE prophylaxis.

  • VTE prophylaxis significantly reduced the incidence of VTE up to 180 days postdischarge and prolonged median time to VTE development.

  • Significantly higher total medical costs were incurred in patients developing VTE or major or minor bleeding.


  • Greater emphasis should be placed on ensuring that at-risk medical patients receive VTE prophylaxis to reduce VTE events and associated costs.
Venous thromboembolism (VTE) is a significant medical problem, with an estimated 200,000 to 600,000 Americans developing VTE each year.1 It is estimated that more than three-fourths of hospitalized patients in the United States have at least 1 risk factor for VTE and 48% have 2 or more risk factors.2 VTE risk is lower in medical patients than in surgical patients, but still substantial (10%-20%).3 In addition, there is increasing evidence that medical patients are less likely than surgical patients to receive thromboprophylaxis, even when it is indicated or recommended.4 In the US cohort from the multinational Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting (ENDORSE) study, 48% of medical patients at risk of VTE received the recommended prophylaxis, compared with 71% of at-risk surgical patients.4 Postoperative VTE has been clearly shown to increase length of hospital stay, medical costs, and mortality,5 but far less is known about the impact VTE has on medical inpatients.

The aim of this study was to analyze the effect of pharmacologic VTE prophylaxis among medical inpatients on the incidence and timing of VTE, readmission due to VTE, bleeding events, and cost of care in the 30, 90, and 180 days in the postdischarge period after the initial (index) admission.


Subjects and Databases

This was a retrospective analysis of patient-level data from the MarketScan Hospital Drug Database (HDD) and linked outpatient files from the MarketScan Commercial and Medicare Supplemental Database from Thomson Reuters for calendar years 2005 to 2007. This is a proprietary database containing the largest collection of US employer-based patient data. Inpatient, outpatient, pharmacy, and enrollment data from MarketScan, together with linked HDD data, were used in this study. Data from 172 hospitals were identifiable for linkage in both hospital and claims databases and covered a geographically diverse area and both public and private health plans. These databases capture clinical and prescription data for the full continuum of care, including physician office visits; hospital stays; retail, mail order, and specialty pharmacies; and carve-out care.

Hospital data comprised submitted claims linked to detailed service-level hospital bills for each admission. Outpatient claims data were matched to each admission using the following patient level identifiers: date of admission, date of discharge, age, gender, and principal diagnosis. Admissions not uniquely identified by this key set of variables were excluded.

The study population consisted of all patients admitted to hospital with a primary diagnosis of chronic heart failure (CHF), thromboembolic stroke, severe lung disease, acute infection, or cancer, based on the International Classification of Diseases, Ninth Revision (ICD-9) codes (see eAppendix A, available at during calendar years 2005 to 2007. This was defined as the index hospitalization. The population was grouped into 2 cohorts: those who developed VTE during index hospitalization and those who did not. VTE during hospitalization was identified by the presence of ICD-9 codes for deep vein thrombosis (DVT; 451.1x-451.81, 451.83-

451.9x, 452.xx, 453.2-453.9x) or pulmonary embolism ([PE] 415.1x) on hospital records. In order to ensure that patients were not erroneously designated as having VTE, true VTE was defined as any VTE event for which anticoagulant therapy was prescribed within 15 days of diagnosis.6 In accordance with current privacy rule guidelines, no patient’s identity or medical records were disclosed, except in compliance with applicable law.


Patient age, gender, and comorbidity data were collected at the index hospitalization. Comorbidity information included the Charlson Comorbidity Index,7 the Elixhauser Comorbidity Index,8 and a primary or secondary diagnosis (based on ICD-9 or ICD-9-CM codes) of congestive heart failure, peripheral arterial disease, acute coronary syndromes, hyperthyroidism, obesity, diabetes, hypertension, ischemic or hemorrhagic stroke, noncentral nervous system systemic embolism, transient ischemic attack, catheter ablation, dyspepsia, or preperiod VTE (see eAppendix B). The preperiod began 180 days before the index event (date of hospital admission).

Outcomes were analyzed according to whether or not patients received any anticoagulant prophylaxis prior to VTE or true VTE diagnosis. In addition, the following prophylactic treatment groups were identified: low molecular weight heparin (LMWH) only; warfarin only; unfractionated heparin (UFH) only; fondaparinux; LMWH + warfarin; UFH + warfarin. The drug use observation period was defined as time from admission for the index hospitalization until 30 days after index hospital discharge.

All outcomes were measured from the index admission date up to 180 days postdischarge or death, whichever occurred first. These outcomes were: the number of VTE and true VTE events; time to the VTE event; length of hospital stay (calculated at patient level); the number of major or minor bleeding events using ICD-9-CM codes (see eAppendix C); the number of patients readmitted for true VTE within 30, 90, and 180 days after index hospital discharge, based on subsequent hospital admission diagnosis of true VTE, or primary or secondary diagnosis of true VTE within 1 to 2 days of subsequent hospital admission; the number of patients readmitted with major bleeding within 30, 90, and 180 days after index hospital discharge, based on subsequent hospital admission diagnosis (primary or secondary) of major bleeding, or primary or secondary diagnosis of major bleeding 1 week before or 1 week after subsequent hospital admission; discharge status (ie, home, short-term hospital stay,

transfer to other facility, miscellaneous); and all-cause healthcare costs paid by the patient and health plan. These costs were computed for medical services (inpatient stay, emergency department visits, and ambulatory care, including physician visits and other outpatient services), pharmacy dispensing, and total combined costs. Prices were adjusted using the annual medical care component of the consumer price index to reflect inflation between the year of the claim and 2007.

Statistical Methods

All study variables, including baseline and outcome measures, were analyzed descriptively as numbers and percentages for dichotomous and polychotomous variables, and as means, medians, standard deviations (SDs), and percentiles for continuous variables. Bivariate comparisons of baseline variables and outcomes were made using the appropriate test (t test, Mann-Whitney U test, or χ2 test), depending on the distribution of the variable. Standardized differences were calculated. The time to VTE event was calculated using Kaplan-Meier curves and analyzed using Cox regressions. A multivariable risk adjustment model was undertaken to estimate outcome measures, incorporating age, gender, region, baseline Elixhauser Comorbidity Index, CHF, thromboembolic stroke, severe lung disease, acute infection, and cancer as confounding factors. Total costs were estimated using log transformation and general linear models, depending on the distribution and presence of heteroskedasticity.


Study Population

The study cohort comprised 13,293 medically ill hospitalized patients (Table 1). The most common reasons for hospitalization were severe lung disease (n = 4473; 33.65%) and cancer (n = 3050; 22.94%). The mean (SD) age of the cohort was 66.5 (17.0) years; 48% of patients were male. Patients with CHF or stroke were older than those in other subgroups (Table 1). The cancer subgroup had the highest proportion of patients with an Elixhauser Comorbidity Index >2 (16%). Overall, 399 patients (3.0%) had experienced a VTE in the 6 months preceding the index hospitalization.

Thromboprophylaxis Used

During the index hospitalization, 7127 patients (53.6%) received thromboembolic prophylaxis and 6166 (46.4%) did not. The most commonly prescribed agents were UFH (n = 3531) or LMWH (n = 3390), followed by warfarin (n = 1629); few patients (n = 42) received fondaparinux. The duration of treatment was longest for warfarin, with a mean of 21.49 days compared with 12.98 days for fondaparinux, 6.30 days for LMWH, and 5.24 days for UFH.

Events During Hospitalization

Of the 7127 patients who received any anticoagulant prophylaxis, 4 (0.06%) developed a true VTE, compared with 212 (3.44%) of the 6166 patients who did not receive any anticoagulant prophylaxis (P <.00001; Table 2). Patients who did not fall into any of the 6 anticoagulant categories described in columns 3 through 8 were included in column 2, “Any Anticoagulant.” The patient number for this category will therefore be greater than the total for the 6 treatment categories specified.

Overall, major bleeding developed in 37 (0.52%) patients receiving VTE prophylaxis and 42 (0.68%) receiving no prophylaxis (P = .226); the corresponding rates of minor bleeding were 373 (5.23%) and 364 (5.90%), respectively (P =.0924). With the exception of patients receiving LMWH + warfarin, who had a major bleeding rate of 1.57%, major bleeding occurred in <.6% of patients receiving any of the other anticoagulant therapies. The rate of major bleeding was significantly higher in patients receiving LMWH + warfarin versus LMWH alone (1.57% vs 0.21%; P = .0002; Table 2). Minor bleeding occurred in 4.4% to 7.4% of patients across all groups (including those receiving no VTE thromboprophylaxis), and there were no significant differences between groups (Table 2). Results were similar in the risk-adjusted analysis, except

that the minor bleeding rate was significantly higher with UFH + warfarin versus LMWH alone (P = .0013; Table 2).

Events After Discharge

Postdischarge event rates are shown in Table 3. Receipt of any anticoagulant prophylaxis significantly reduced the rate of VTE occurring up to 30, 90, or 180 days after index discharge compared with no thromboprophylaxis (P <.00001). LMWH + warfarin was associated with a significantly increased rate of VTE at 30, 90, and 180 days postdischarge versus LMWH alone (P <.005). It should be noted that for each category of events, the duration of continuous enrollment post hospital discharge differed (30, 90, and 180 days); consequently, the number of patients enrolled diminished as the duration of continuous enrollment increased.

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