Article

Barriers to the use of outpatient enoxaparin therapy in patients with deep venous thrombosis

Barriers to the use of outpatient enoxaparin therapy in patients with deep venous thrombosisB

Nathan I. Shapiro MD, MPHa,*, Jeffrey Spear BSa, Susan Sheehy RN, MSa,

Jeremy Brown MDb, Jonathan A. Edlow MDa

aDepartment of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA

bDepartment of Emergency Medicine, George Washington University, Washington, DC 20052, USA

Received 13 October 2003; accepted 18 January 2004

Abstract

Objective: To establish a Clinical pathway for outpatient enoxaparin therapy in Deep venous thrombosis and then characterize its implementation and barriers to use.

Procedure: Single institution, prospective, observational study of consecutive adult emergency department patients (age z18 years) who had a diagnosis of DVT. A clinical pathway was created to facilitate Outpatient therapy with enoxaparin, and then all patients with DVT were enrolled and studied.

Results: A total of 97/98 (99%) eligible patients were enrolled. Among 97 patients, 29 (30%) were successfully started on the outpatient enoxaparin therapy approach. Of the 68 (70%) patients not started on the outpatient therapy, 19 (20%) patients had contraindications to anticoagulant therapy, 33 (34%) had other indications for hospitalization, 6 (6%) were unable to reliably self-inject, and 10 (10%) patients had a primary care physician or emergency physician who rejected the outpatient approach.

Conclusions: The establishment of an organized DVT pathway for outpatient enoxaparin may facilitate home therapy; however, there will remain reasons that make hospital admission unavoidable in some patients.

D 2005

Introduction

Each year there are an estimated 250 000 patients diagnosed with Deep venous thrombosis . Many of these patients present to the emergency department (ED)

B Abstract presentation at the American College of Emergency Phy- sicians Scientific Assembly Research Forum, October 2003, Boston, Mass.

* Corresponding author. Tel.: +1 617 754 2323; fax: +1 617 754 2350.

E-mail address: [email protected] (N.I. Shapiro).

with this as their isolated problem. There have been numerous studies and meta-analyses that have confirmed the safety and efficacy of the low-molecular-weight heparins (LMWHs) as a therapy for this disease [1-9]. Because LMWH is easily administered subcutaneously once or twice a day, it may be used as a home therapy with little monitoring. This approach has been demonstrated to be cost effective, reducing both Healthcare costs and hospital length of stay [4,10-12]. Finally, patients have been shown to prefer home therapy [6]. In uncomplicated patients, this safe,

0735-6757/$ – see front matter D 2005 doi:10.1016/j.ajem.2004.09.028

effective, easy to implement therapy represents an overall benefit to the healthcare system.

However, despite the literature-based consensus that this is a safe and effective therapy, outpatient LMWHs are not always used to treat this disease. The reasons for not implementing therapy may include difficulty in arranging therapy, lack of education to the provider on how to set up outpatient therapy, lack of confidence in outpatient therapy by physician or patient, and insurance issues in paying for the medicine. Other factors that may not be overcome include admissions for the work-up of other conditions, critical illness, or contraindication to therapy. There is opportunity to provide support and education to enhance the use of outpatient therapy.

To conduct this study, we designed a clinical pathway for using outpatient LMWH therapy. Once the pathway was in place, we sought to accomplish the following Study objectives: (1) to determine the frequency with which a clinical pathway for the outpatient treatment of DVT using enoxaparin is used to discharge eligible patients from the ED;

(2) to characterize the reasons why patients with DVT are hospitalized; and (3) to identify possible solutions to enhance the use of outpatient Treatment protocols.

Methods

Design

This was a prospective, observational study performed between May 31, 2001, and August 15, 2002. The study setting was the ED of Beth Israel Deaconess Medical Center, an urban university referral center with approxi- mately 50000 visits per year. Eligible patients were any adult patient (age z18 years) seen in the ED with a diagnosis of DVT. Diagnosis of DVT was detected by ultrasonography. Patients were enrolled either at the time of the ED visit or after hospital admission using only information recorded at the time of the ED visit. Information from the ED visit and the reasons why clinical pathways were or were not implemented were collected on all patients. The reason for not using the pathway was determined through data sheets filled out at the time of the visit, chart review, and physician interview.

Creation of an outpatient protocol

A clinical pathway was created to enable the clinician to easily implement outpatient enoxaparin therapy from the ED. This protocol consisted of a flow sheet reviewing exclusion criteria for enoxaparin, a checklist that guides the clinician through the protocol for implementation of outpatient enoxaparin, and a home therapy kit. The clinical pathway for implementation of therapy included a checklist for baseline laboratory testing, dosing guidelines for both enoxaparin and warfarin, and a list of pharmacies routinely carrying enoxaparin and their hours, as well as guidelines for follow-up testing. The home therapy kit included additional

teaching materials, a needle box, and an Instructional videotape. Once a patient was identified as appropriate for therapy, the physician used the pathway, particularly the checklist, to implement home therapy. The checklist also described other available resources. The resources included a learning center that provided teaching to patients during business hours (9 am to 5 pm, Monday through Friday), an ED case manager who could help coordinate care, and a research assistant who was available to answer questions and guide clinicians through the protocol as needed.

Data collection

Data collected included demographic data, means of diagnosis, risk factors, who administered therapy, who taught the patient how to perform the injection, contra- indications, reasons the eligible patients did not go on therapy, location of treatment, and ability to self-inject. This information was collected through physician and patient interview and chart review. For the admitted patients, data regarding their hospital course and their usage of enoxaparin and the learning center were also obtained.

The electronic ED patient log was used to ensure consecutive enrollment of patients, thus, preventing selection bias. A review of the ED log as well as an electronic search occurred concurrently during the study period to assure that all eligible patients were enrolled. Of the 98 patients eligible for enrollment, 97 (99%) patients were enrolled.

Statistical methods

In this descriptive study, the admission decision, usage of the protocol, barriers to enoxaparin therapy, and any other descriptions of usage are reported using percentages without statistical comparison. Fisher exact test and v2 analysis were used for any pairwise comparisons as appropriate.

Results

There were a total of 97 patients with DVT enrolled in the study. The mean age was 60.7 years (SD F 17) of which

Table 1 Population demographics

DVT (%) (n = 97)

Age (mean F SD)

60.7

(16.8)

Female sex

57

(59)

Risk factors

Chronic immobility

17

(18)

Current oral contraceptive use

8

(8)

Recent surgery

15

(16)

Malignancy

33

(34)

Diabetes

15

(16)

extremity trauma

7

(7)

Smoker

21

(22)

Prior thromboembolism

20

(21)

Travel

5

(5)

Immobile

17

(18)

Fig. 1 Patient eligibility and management.

59% were women. The demographics and risk factors for patients with DVT are shown (Table 1). Fig. 1 shows the breakdown by diagnosis, patient disposition, and reasons the outpatient protocol was not used.

Among the 97 patients with DVT, there were 39 (40%) who were eligible for outpatient therapy and could inject as an outpatient. Of the 58 who were ineligible, 19 (33%)

had contraindications to anticoagulant therapy (Table 2),

33 (57%) had other medical indications for admission, and 6 (10%) were unable to inject as outpatients (Table 3; Fig. 1). Of the 39 eligible patients, 29 (74%) were successfully started on the outpatient protocol, whereas 10 (26%) were admitted to the hospital (Table 4). For the 10 who were admitted, the reasons for admission were ED physician preference without justification for 6 patients, Primary care physician preference without justifi- cation for 2 patients, and a hypercoagulable work-up for 2 patients. Of these, 5/10 (50%) were discharged home on enoxaparin the following day. Among the 68 patients admitted for any reason, 29 (43%) were ultimately dis- charged home on enoxaparin. Thus, a total of 58/97 (60%) of

Table 2 Nineteen patients with DVT that have contraindication to outpatient enoxaparin

n (%) Contraindication

14 (74) Concern for bleeding risk (coagulopathy, active ulcer disease, liver disease)

2 (11) Already anticoagulated for prior venous thromboembolism

1 (5) Recent gastrointestinal bleed

1 (5) Renal insufficiency

1 (5) History of Heparin-induced thrombocytopenia

Table 3 Seven patients unable to inject as outpatient

n

(%)

Reason

2

(29)

Fear of injection

2

(29)

language barrier to teaching

2

(29)

Patient unwilling

Table 4 Ten eligible patients admitted to the hospital

n

(%)

Reason

6

(60)

ED physician preference without justification

2

(20)

PCP preference without justification

2

(20)

Hypercoagulable work-up

patients with DVT were treated with enoxaparin as part of their therapy.

Discussion

This study examined the feasibility of creating a protocol for the use of enoxaparin for outpatient therapy for DVT and characterized the reasons this pathway was not used for eligible patients. Prerequisite to initiating this study was the creation of a clinical care pathway that coordinated available resources and enabled an outpatient approach. It provided an organized approach to guide the physician and nursing staff through the process of instituting outpatient therapy. The outpatient pathway made it easier for the physician to start patients on therapy by providing exclusion criteria, a checklist of laboratory tests that needed to be performed, phone numbers for pharmacies carrying enoxaparin regu- larly and after hours, and guidelines for the follow-up Blood draws and initiation of Warfarin therapy. It provided the clinician with the assurance that they were correctly initiating therapy. In addition, a research assistant was available by telephone who could answer additional ques- tions about the procedure of instituting therapy. We found that in several instances a brief overview of the process and instructing physicians to refer to the prepared pathway reinforced the ease with which this could be done. The pathway gave added confidence to the physician to institute outpatient enoxaparin therapy so that they felt confident with starting therapy. During the hours of 9 am to 5 pm, Monday through Friday, a learning center was available that could provide additional teaching. Patients could either go directly to the learning center, or, during Off hours, receive their first dose of medication in the ED and follow-up the next morning for their next dose and additional teaching. Creating a step-by-step pathway and promoting access to the available resources more easily instituted outpatient therapy.

A high proportion (74%) of eligible patients with DVT were started on therapy. Although 74% of eligible patients were successfully started on outpatient therapy, there were an additional 10 (26%) eligible patients who were admitted despite their eligibility for outpatient therapy. The reasons were primarily related to the ED physician choosing not to institute therapy. Specific reasons included lack of time for teaching in a busy ED, lack of knowledge about the protocol and how to institute outpatient therapy, and inability to arrange reliable follow-up with a PCP. Primary care physician choice was also a reason for not instituting therapy. Specific

reasons were lack of confidence in the pathway and concerns about the ability of the patient to receive proper teaching. We did find that 50% of patients who were admitted for no clear reason were ultimately discharged within 48 hours without any other significant interventions besides enoxaparin therapy; thus, they probably could have been discharged from the ED. We believe that continuing the educational process, as well as assuring that resources are available to help institute therapy, will continue to increase the usage of the protocol.

There were a total of 16 patients admitted to the hospital in which outpatient enoxaparin therapy would have been medically appropriate. Ten patients simply did not have outpatient therapy arranged without a specific reason, whereas 6 patients were unable to inject themselves or to have reliable arrangements made. These 16 patients had a total of 37 hospital days for an average length of stay of 2.3 days, and the average cost of hospitalization was $2188 per patient. Using these figures, the total savings realized in this study by treating the 29 patients with the home protocol may be estimated to be $63452. An additional $35008 would have been saved if the barriers could have been overcome and the additional 16 patients would have used outpatient therapy.

Another potential problem that we identified was the structure of reimbursement by Medicare. Medicare does not provide reimbursement for enoxaparin, but will cover Inpatient hospitalization expenses. Therefore, the patient has to cover the costs of the medication if they are sent home, but Medicare will cover the higher costs of a hospital admission. We would advocate for this policy being reexamined as it would be more cost-effective and prevent unnecessary hospitalizations.

There are a number of studies and meta-analyses that confirm the efficacy and safety of enoxaparin for DVT [1-9]. Treatment of DVT as an outpatient therapy with LMWH has been shown to be safe and effective in several large, well- established, prospective, multicenter trials [4,6]. Both Levine et al and Koopman et al used 3 outcome measures: efficacy (recurrent venous thromboembolism b 90 days), safety (severe bleeding, based on predefined parameters), and all cause 90-day mortality rate to demonstrate the equivalence between therapies. A meta-analysis of 13 studies by Siragusa et al [9] shows a significant relative risk reduction of these outcomes with level 1 studies (prospective, randomized, methodologically strong) and trends toward benefit when all studies are pooled. A separate meta-analysis of 17 studies by Leizorovicz et al [7] demonstrated trends toward the benefit of LMWH over unfractionated heparin. Although the proof for benefit is not concrete, there is little evidence to dispute at least equivalence between LMWH and unfractionated heparin.

The following year in the same journal, two other groups of European investigators, using the same outcome measures, extended these findings to selected patients with pulmonary embolism (PE) [13,14]. Others in North America have also

confirmed these studies [15]. Nevertheless, because most US physicians are not yet comfortable with using outpatient LMWH therapy for patients with PE, we elected to focus on those with isolated DVT, where the science, the FDA- approved indications, and the sentiment are concordant. We did collect data on these patients during our enrollment period and found that 44/48 (92%) of patients with PE were admitted, whereas 3 were treated in a nursing home and 1 discharged. The primary reason given by clinicians was simply that they were not comfortable in treating patients with PE as outpatients. Thus, until physicians are more comfortable with the safety demonstrated in the literature, outpatient treatment is less likely to be used for PE.

In this study we were able to successfully initiate a protocol for the use of outpatient treatment using enoxaparin therapy for patients with DVT from the ED. We character- ized the reasons why the protocol was not used for patients who were eligible for home therapy. By providing a structured pathway and making available the resources to institute therapy, the protocol was used in a high proportion of eligible patients. Using this information, we may continue to provide education and support to encourage the use of this home treatment that has been proven to be safe and effective.

Acknowledgment

This study was funded by an investigator-initiated research grant from Aventis Pharmaceuticals, Bridgewater, NJ. The authors thank Brian McGrath for help with data collection and storage.

References

  1. Bratt G, Aberg W, Johansson M, et al. Two daily subcutaneous injections of fragmin as compared with intravenous standard heparin in the treatment of deep venous thrombosis (DVT). Thromb Haemost 1990;64:506 – 10.
  2. Simonneau G, Charbonnier B, Decousus H, et al. Subcutaneous low- molecular-weight heparin compared with continuous Intravenous unfractionated heparin in the treatment of proximal deep vein thrombosis. Arch Intern Med 1993;153:1541 – 6.
  3. Hull RD, Raskob GE, Pineo GF, et al. Subcutaneous low-molecular- weight heparin compared with continuous Intravenous heparin in the treatment of proximal-vein thrombosis. N Engl J Med 1992;326: 975 – 82.
  4. Levine M, Gent M, Hirsh J, et al. A comparison of low-molecular- weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis. N Engl J Med 1996;334:677 – 81.
  5. Prandoni P, Lensing AW, Buller HR, et al. Comparison of subcuta- neous low-molecular-weight heparin with intravenous standard hepa- rin in proximal deep-vein thrombosis. Lancet 1992;339:441 – 5.
  6. Koopman MM, Prandoni P, Piovella F, et al. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. The Tasman Study Group. N Engl J Med 1996;334:682 – 7.
  7. Leizorovicz A, Simonneau G, Decousus H, et al. Comparison of efficacy and safety of low-molecular-weight heparins and unfractio- nated heparin in initial treatment of deep venous thrombosis: a meta- analysis. BMJ 1994;309:299 – 304.
  8. Lensing AW, Prins MH, Davidson BL, et al. Treatment of deep venous thrombosis with low-molecular-weight heparins. A meta-analysis. Arch Intern Med 1995;155:601 – 7.
  9. Siragusa S, Cosmi B, Piovella F, et al. Low-molecular-weight heparins and unfractionated heparin in the treatment of patients with acute venous thromboembolism: results of a meta-analysis. Am J Med 1996; 100:269 – 77.
  10. Hull RD, Raskob GE, Rosenbloom D, et al. Treatment of proximal vein thrombosis with subcutaneous low-molecular-weight heparin vs. intravenous heparin. An economic perspective. Arch Intern Med 1997; 157:289 – 94.
  11. White RH, Zhou H, Romano PS. Length of hospital stay for treatment of deep venous thrombosis and the incidence of recurrent thrombo- embolism. Arch Intern Med 1998;158:1005 – 10.
  12. Lindmarker P, Holmstrom M. Use of low-molecular-weight heparin (dalteparin), once daily, for the treatment of deep vein thrombosis. A feasibility and health economic study in an Outpatient setting. Swedish Venous Thrombosis Dalteparin Trial Group. J Intern Med 1996;240: 395 – 401.
  13. The Columbus Investigators. Low-molecular-weight heparin in the treatment of patients with venous thromboembolism. N Engl J Med 1997;337:657 – 62.
  14. Simonneau G, Sors H, Charbonnier B, et al. A comparison of low- molecular-weight heparin with unfractionated heparin for acute pulmonary embolism. The THESEE Study Group. Tinzaparine ou Heparine Standard: evaluations dans l’Embolie Pulmonaire. N Engl J Med 1997;337:663 – 9.
  15. Hull RD, Raskob GE, Brant RF, et al. Low-molecular-weight heparin vs heparin in the treatment of patients with pulmonary embolism. American-Canadian Thrombosis Study Group. Arch Intern Med 2000;160:229 – 36.

Leave a Reply

Your email address will not be published. Required fields are marked *