Outpatient Treatment of Deep Vein Thrombosis in the United States: The Reasons for Geographic and Racial Differences in Stroke Study

Venous thromboembolism (VTE) is a common medical condition comprising deep vein thrombosis (DVT) and pulmonary embolism (PE). Estimates of the incidence of DVT in the United States vary between 0.5 and 1.5 cases per 1000 person-years.¹ Left untreated, roughly 50% of DVT patients progress to a PE, of whom 10% to 25% die within 3 months.²

Since the 1990s, multiple randomized controlled studies^3-5 demonstrated the safety and efficacy of outpatient treatment for selected DVT patients with low molecular weight heparin and warfarin. The United States Food and Drug Administration approved enoxaparin, a low molecular weight heparin for outpatient use in 1998,⁶ and by the end of the decade, multiple treatment guidelines for VTE acknowledged the safety of outpatient treatment of DVT with low molecular weight heparin in selected patients.^7-9 Recently, the approval of direct oral anticoagulants (DOACs) by the Food and Drug Administration allows an all-oral treatment regimen for VTE, which could further facilitate outpatient treatment of DVT.

Costs associated with treatment of VTE are enormous. For outpatient treatment, researchers differ on individual estimates of cost savings associated with outpatient DVT management, but most report a cost savings of several thousand dollars per patient treated as an outpatient compared with as an inpatient.^6,10 Given the incidence of DVT, reducing costs while maintaining a high quality of care in even a small percentage of DVT patients would result in significant healthcare cost savings as well as increased convenience for patients.

Despite high-quality evidence supporting the efficacy and safety of outpatient DVT treatment, little is known about the adoption of outpatient DVT treatment in the United States. Several studies that have been published were limited to single hospitals and were small in size^11,12 or limited to a cohort of patients already diagnosed with DVT.¹³

The purpose of this study was to report the frequency of outpatient treatment of DVT in the United States and describe patient characteristics associated with outpatient treatment. Information was gathered from The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a contemporary cohort study of more than 30,000 patients residing in the contiguous United States with racial and geographic diversity. We hypothesized that an individual’s age, sex, race, region of residence, urban or rural residence, education level, and personal income would be associated with outpatient treatment. Results would allow the implementation of interventions to promote the appropriate use of outpatient treatment in order to reduce healthcare costs and increase patient convenience without compromising safety or efficacy of care.

Cohort Characteristics

VTE events were ascertained in the REGARDS cohort, a prospective, longitudinal cohort study investigating the causes of racial and geographic disparities in stroke and cognitive decline.¹⁴ Between 2003 and 2007, there were 30,239 participants in the contiguous United States ≥45 years old enrolled in REGARDS. By design, 55% were female, 41% were black, the mean age was 65 years, and 56% lived in the southeastern United States. Participants were recruited from a commercial list by mail and telephone contact followed by verbal consent. A telephone interview was followed by an in-home examination, including obtaining written informed consent. On study entry, many participants had comorbid conditions, including 8% with reported atrial fibrillation, 56% receiving treatment for hypertension, 22% receiving treatment for diabetes, 3.7% taking warfarin, and 14% who were actively smoking.^15,16 Participants were only excluded if they had active cancer, stated a self-reported race other than white or black, were unable to converse in English, had cognitive impairment as judged by the telephone interviewer, or were residing in or on the waiting list for a nursing home. Study methods were reviewed and approved by the institutional review boards at each study institution and have been published elsewhere.¹⁴

Event Ascertainment and Definitions

DVT event ascertainment is complete through 2011, with identification by telephone interview, review of reported hospitalizations, and review of deaths.¹⁷ Questionnaires in similar epidemiological studies have 98% specificity and >70% sensitivity for ascertaining VTE events.¹⁸ A research nurse reviewed the text and recorded each reported hospitalization through 2011. Any report of a blood clot in the legs, arms, or lungs was a potential case for physician review. Medical records were retrieved for up to 1 year before and 1 year after potential events. Retrieved records were used to help guide further record retrieval if they did not contain the primary VTE event. Primary inpatient and outpatient records including history and physical examinations, discharge summaries, imaging reports (to include limb ultrasounds, computed tomography scans, and magnetic resonance imaging), autopsies, and outpatient notes were retrieved using up to 3 attempts.¹⁹ Using all available information, characteristics of the VTE event and treatment were systematically recorded. For each potential VTE case, two of three physician reviewers abstracted medical records to validate and classify the event. If the physician reviewers disagreed, the third physician would review the case, and if VTE status remained uncertain, cases were discussed and resolved. Race was determined by participant self-report as black or white. Location of residence was defined by geocoding the addresses, and urban or rural status was defined by United States census tract data using rural-urban commuting area codes (RUCA; with rural areas being RUCA codes 4–10).²⁰ Other risk factors were obtained through surveys, telephone interviews, or in-home visits.¹⁴