Outpatient Management of Stable Acute Pulmonary Embolism

KEYWORDS: Anticoagulation; Pharmacotherapy; Pulmonary embolism; Risk stratification; Treatment; Venous thromboembolism Deep vein thrombosis DVT and pulmonary embolism PE are manifestatio

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Outpatient Management of Stable Acute Pulmonary

Embolism: Proposed Accelerated Pathway for Risk

Stratification

Amjad AlMahameed, MD, MPH, a and Teresa L Carman, MD b

a

Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA; and b

Section

of Vascular Medicine, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA

ABSTRACT

Pulmonary embolism (PE) is a major health problem and a cause of worldwide morbidity and mortality.

The current standard therapy for acute PE encourages admitting patients to the hospital for administration

of parenteral anticoagulation therapy as a bridge to oral vitamin K antagonists Prognostic models that

identify patients with stable (nonmassive) acute PE (SPE) who are at low risk for adverse outcome have

recently been reported Based on these risk stratification models, hospital-based therapy is warranted for

patients with PE who meet the criteria associated with a high risk for adverse outcome However, a

growing body of evidence suggests the feasibility of partial outpatient management and accelerated

hospital discharge (AHD) in a subset of patients with SPE Prospective validation of these risk stratification

KEYWORDS: Anticoagulation; Pharmacotherapy; Pulmonary embolism; Risk stratification; Treatment; Venous

thromboembolism

Deep vein thrombosis (DVT) and pulmonary embolism

(PE) are manifestations of the same disease process

re-ferred to collectively as venous thromboembolism

(VTE) Despite increased awareness and wider

employ-ment of reliable thromboprophylactic strategies, the

in-cidence of first-time symptomatic VTE remains high at

71 to 117 cases per 110,000 population.1 Up to 33% of all

patients with symptomatic DVT manifest PE at the time

of presentation Nearly 50% of individuals with proximal

(i.e., suprapopliteal or above-the-knee) DVT have

radio-graphic evidence of a coexistent PE,2 and most fatal

emboli are likely to arise from this region.3Although the

risk of embolization may be lower with untreated distal

(i.e., calf vein or infrapopliteal) DVT, proximal

propa-gation is seen in as many as 25% of such thrombi, further increasing the risk for PE Patients with a history of PE are almost 4 times more likely to die of recurrent VTE in the following year than are patients who are treated for DVT alone.4

It is estimated that about 237,000 nonfatal and 294,000 fatal cases of PE occur in the United States each year.5A total of 34% of VTE-related deaths were due to sudden massive PE and 59% followed undiagnosed PE

PE presents with a wide clinical spectrum and largely nonspecific symptoms; therefore, timely diagnosis re-quires a high degree of clinical suspicion Studies suggest that 55% to 94% of PEs in medical patients are not diagnosed until autopsy.6,7 These numbers most likely have been underestimated because autopsies are not rou-tinely conducted in contemporary practice It has been suggested that up to 27% to 68% of fatal PE cases are potentially preventable.8 Thus, rigorously screening for VTE risk factors and implementing effective thrombo-prophylaxis, along with prompt diagnosis and early ther-apy of suspected cases, is warranted

Please see the Conflict of Interest section at the end of this article.

Requests for reprints should be addressed to Amjad AlMahameed, MD,

MPH, Division of Cardiology, Beth Israel Deaconess Medical Center,

Harvard Medical School, 1 Deaconess Road (Baker 4), Boston,

Massachu-setts 02115.

E-mail address: aalmaham@bidmc.harvard.edu.

doi:10.1016/j.amjmed.2007.08.010

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RISK STRATIFICATION

Acute PE generally can be classified as either massive PE or

nonmassive SPE.9 Patients with massive acute PE have a

uniformly poor prognosis and the first few hours is the

critical period when the majority of deaths occur It is

during this narrow window when prompt diagnosis and

rigorous treatment strategies can save lives.10

Hemody-namic instability with systemic hypotension, cardiogenic

shock, severe dyspnea, or respiratory failure at the time of

presentation defines a physiologically massive PE Massive

acute PE is associated with increased risk for early

mortal-ity.9,10According to reports from the International

Cooper-ative Pulmonary Embolism Registry (ICOPER), the

inci-dence of mortality at 3 months in patients with

hemodynamic instability was 58% compared with 15% in

patients who were hemodynamically stable.11

Radiograph-ically large PE has been defined as angiographic obstruction

of ⱖ50% or ⱖ2 lobar arteries.10,12

SPE, on the other hand, is not associated with

hemody-namic instability or respiratory failure and has a much lower

risk for mortality (⬍5%).9

These patients may be asymp-tomatic, or may present with mild or moderate dyspnea,

cough, pleuritic chest pain, or other clinical complaints The

mortality in SPE is significantly higher (26%) if these

pa-tients experience recurrent PE.9SPE remains a serious

con-dition and clinicians should focus on preventing recurrent

emboli, particularly early after the initial PE, and not be

deceived into inaction by the low initial mortality rate

Using clinical factors alone, many patients presenting

with acute PE can be classified as either unstable, thus

requiring intensive inhospital therapy, or stable and at low

risk for adverse events and potentially amenable to

accel-erated hospital discharge (AHD) Table 113–26outlines

im-portant predictors of adverse outcomes in patients with

acute PE The Geneva Risk Score (GRS) is a clinical

scor-ing system (Table 216) that has undergone both internal and

external validation The GRS was developed using

multi-variate analysis of clinical factors present at the time of

admission in 296 consecutive patients with confirmed PE.16

Independent predictors of adverse outcome were history of

cancer, congestive heart failure, previous DVT, systolic

blood pressure⬍100 mm Hg, arterial oxygen pressure ⬍8

kPa, and acute DVT on ultrasonography at the time of

presentation Risk scores were assigned to each variable and

cross-validated (Table 2) During the 3-month follow-up,

2.2% (4 of 180) of low-risk patients (a score ⱕ2)

experi-enced an adverse clinical outcome, including death,

recur-rent thromboembolism, or bleeding, compared with 26% in

high-risk patients (score of ⱖ3).16

A recent retrospective study externally validated the GRS for identifying patients

with acute PE who were at low risk for an adverse clinical

outcome.15

A second retrospective study derived a prediction rule

for PE outcomes by randomly selecting 10,354 of 15,531

individuals discharged from 186 US hospitals with a

diag-nosis of PE.13In all, 11 demographic, comorbid conditions

and physical examination findings were validated as predic-tors of 30-day all-cause mortality and other severe nonfatal complications, such as cardiogenic shock and cardiopulmo-nary arrest during hospitalization (Table 1, see clinical

Table 1 Predictor variables of adverse outcomes in patients with acute pulmonary embolism

● Clinical parameters 13–16

—Age ⬎70 yr at onset

—Heart failure

—Cancer

—Previous DVT

—Chronic lung disease

—Chronic renal disease

—Cerebrovascular disease (TIA or stroke)

—Systemic arterial hypotension (SBP ⬍100 mm Hg)

—Hypoxemia (O2saturation ⬍90% with/without O 2

supplementation)

—Tachycardia (HR ⱖ 110 beats/min)

● Parameters for right ventricular dysfunction 17–23

—Electrocardiogram

X T-wave inversion in leads V1–V4

X New right bundle branch block

X S1Q3T3

—Echocardiographic

X RV hypokinesis

X Persistent pulmonary hypertension

X Patent foramen ovale

X Free-floating right-heart thrombus

—CT scan

X RV/LV ratio ⬎0.9 on the reconstructed CT 4-chamber view identifies patients at increased risk for early death

● Cardiospecific biomarkers 24–26

—Pro-BNP

X ⬍50 pg/mL identifies 95% of patients with a benign clinical course

—Troponin (positive troponin I or T in the absence of primary cardiac ischemia)

X Indicates RV microinfarction

X The higher the value, the worse the prognosis

BNP ⫽ brain natriuretic peptide; CT ⫽ computed tomography; DVT

⫽ deep vein thrombosis; HR ⫽ heart rate; RV ⫽ right ventricular; RV/LV ⫽ right ventricular/left ventricular; SBP ⫽ systolic blood pres-sure; TIA ⫽ transient ischemic attack.

Adapted from Am J Respir Crit Care Med,13Arch Intern Med,14Thromb Haemost,15,16Circulation,17,19,21,22,24,26Ann Intern Med,18Arch Intern Med,20Radiology,23and Eur Heart J.25

Table 2 The Geneva Risk Score

Systolic blood pressure ⬍100 mm Hg ⫹2

DVT ⫽ deep vein thrombosis.

Adapted from Thromb Haemost.16

S19 AlMahameed and Carman Risk Stratification in Outpatient Management of Stable Acute PE

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parameters) More than 20% of patients enrolled in the

study did not present with any of these variables, and thus

were deemed to be at low risk The incidences of 30-day

mortality and serious adverse outcomes in the low-risk

group were low (0% to 1.6% and ⬍1.1%, respectively)

compared with the high-risk group (4.0% to 11.4% and

1.9% to 2.1%, respectively)

Despite the valuable information provided by the initial

clinical assessment, there is a subgroup of patients with PE

who may appear well but decompensate shortly thereafter

owing to right ventricular compromise In this setting

as-sessment of right ventricular function and the use of

biomar-kers may be helpful to further risk stratify these patients

Right ventricular dysfunction (RVD) can be evaluated on

the basis of physical examination, electrocardiography, and

chest computed tomography (CT).19 Moderate or severe

RVD in normotensive patients is an indicator of

physiolog-ically large emboli and is associated with worse

progno-sis,27,28including up to 10% mortality.29Although

echocar-diography may be useful for risk stratification, it should not

be used alone to establish the diagnosis of PE.12,28,30

Tests for cardiospecific biomarkers, in particular cardiac

troponins (cTnT and cTnI) and brain natriuretic peptides

(BNPs) may be used for objective risk stratification of

patients with acute PE (Table 1).19,24 –26,29These tests are

readily available, inexpensive, reproducible, and accurate

Patients with elevated BNP and troponin levels are more

likely to have RVD26,29,31–36and benefit from closer

obser-vation Low BNPs and troponin levels have a high negative

predictive value for inhospital death and other adverse

out-comes,26,29,31,34including the need for pressor support,

me-chanical ventilation, intensive care transfer, and prolonged length of stay These patients may be candidates for AHD.26

Biomarkers should be evaluated both at presentation and after 12 hours because a delayed release (particularly tro-ponin) may be observed after 6 to 12 hours.29,37

In addition to formal clinical assessment, our practice frequently incorporates the use of biomarkers and measures

of RV function (such as echocardiography and CT scan) to further risk stratify patients Recent reports have called for incorporating cardiac biomarkers into PE management de-cision algorithms (Figure 1),19,24,25,29,38 although such a strategy has not been adopted by formal consensus guide-lines.29

GUIDELINES AND CURRENT STANDARDS FOR TREATMENT OF PULMONARY EMBOLISM

The American College of Chest Physicians (ACCP) has developed guidelines for initial treatment of acute PE ( Ta-ble 3).4,39 Although the ACCP recommends considering systemic thrombolysis (grade 2B; see Table 3 for explana-tion of grades) or surgical embolectomy (grade 2C) for patients presenting with massive PE,4,29,40 the use of these therapies in patients with SPE is controversial.40 Surgical embolectomy carries operative mortality ranging from 20%

to 50%, and the incidence of major bleeding complications with thrombolytic therapy is twice that seen in patients treated with heparin alone.40

For nearly half a century, intravenous infusion of unfrac-tionated heparin (UFH) followed by oral administration of warfarin has been the cornerstone of treatment for acute

Figure 1 An integrated approach to the risk stratification of patients with acute pulmonary embolism (PE) BNP ⫽ brain natriuretic peptide; CT ⫽ computed tomography; RV ⫽ right ventricular; 1 ⫽ increase; 2 ⫽ decrease (Reprinted with permission from

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VTE.41The full anticoagulant effects of warfarin are seen

only after 4 to 5 days of administration Thus, in patients

with acute VTE, warfarin must always be administered in

conjunction with a rapidly acting parenteral anticoagulant

UFH has pharmacologically limiting properties, including a

poor dose-response curve and a relatively narrow

therapeu-tic window, requiring close monitoring and frequent dose

adjustments These issues make its use in the outpatient

setting somewhat difficult.42 In addition, in some patients,

UFH may cause immune-mediated thrombocytopenia and

thrombosis.3

The use of newer anticoagulants with better

bioavailabil-ity and more consistent therapeutic response along with

recent advances in risk stratification have led to improved

treatment outcomes in patients with VTE.19 Three

low-molecular-weight heparins (LMWHs), dalteparin,

tinzapa-rin, and enoxapatinzapa-rin, are approved by the US Food and Drug

Administration (FDA) for treatment of acute symptomatic

DVT with or without PE in hospitalized patients Several

reports have been published using LMWHs (including

tin-zaparin, dalteparin, enoxaparin, and nadroparin) to treat acute PE outside the hospital (Table 4).43– 48

Fondaparinux is another anticoagulant that has been ap-proved by the FDA specifically for outpatient treatment of

PE in conjunction with warfarin when initial therapy is administered in the hospital.49It is a synthetic pentasaccha-ride compound that selectively inhibits factor Xa through an antithrombin-mediated mechanism Its relatively long half-life (17 to 21 hours in individuals with normal renal func-tion) allows for once-daily subcutaneous injection using a simplified weight-based dosing The risk of heparin-induced thrombocytopenia with fondaparinux is negligible.50

The efficacy and safety of once-daily subcutaneous fondaparinux for the initial treatment of PE were recently prospectively evaluated in comparison with continuous in-travenous UFH in 2,213 subjects enrolled in the phase 3, randomized Mondial Assessment of Thromboembolism Treatment Initiated by Synthetic Pentasaccharide with Symptomatic Endpoints (MATISSE-PE) trial.51The aim of MATISSE-PE was to compare the rates of VTE recurrence

Table 3 American College of Chest Physicians (ACCP) recommendations for the initial treatment of patients with acute pulmonary embolism (PE)

Grade/Level

of Evidence* Intravenous UFH or

LMWH

Objectively confirmed nonmassive PE Short-term treatment with SC LMWH or IV

UFH

1A High clinical suspicion of PE Treatment with anticoagulants while awaiting

the outcome of diagnostic tests

1C ⫹

Acute nonmassive PE Initial treatment with LMWH or UFH for ⱖ5

days

1C Systemically and locally

administered

thrombolytic drugs

Most patients with PE Recommend against systemic thrombolytic

therapy

1A

Most patients with PE Recommend against use of mechanical

approaches

1C Catheter extraction or

fragmentation

Patients with acute massive PE who are unable to receive thrombolytic therapy

Consider use of mechanical approaches 2C

Pulmonary embolectomy Most patients with PE Recommend against pulmonary embolectomy 1C

Patients with acute massive PE who are unable to receive thrombolytic therapy

Consider pulmonary embolectomy 2C Vena caval interruption In patients with PE with a contraindication

for, or a complication of anticoagulant treatment, as well as in those with recurrent thromboembolism despite adequate anticoagulation

Placement of an inferior vena caval filter 2C

IV ⫽ intravenous; LMWH ⫽ low-molecular-weight heparin; RCT ⫽ randomized clinical trial; SC ⫽ subcutaneous; UFH ⫽ unfractionated heparin.

*Explanation of grades of recommendation and levels of evidence:

● Grade 1: Strong recommendation; certain that benefits do, or do not, outweigh risks, burden, and costs.

● Grade 2: Weaker recommendation; less certain of the magnitude of benefits and the impact of risks, burden, and costs.

● Level of evidence A: RCTs with consistent results.

● Level of evidence B: RCTs with inconsistent results or with major methodologic weaknesses.

● Level of evidence C: Observational studies or from a generalization from 1 group of patients included in RCTs to a different, but somewhat similar, group of patients who did not participate in those trials If generalizations are secure or observational study data are compelling, grade C ⫹ can be designated.

Adapted from Chest.4,39

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Table 4 Prospective studies evaluating outpatient anticoagulation therapy following acute pulmonary embolism (PE)

Wells et al.,

1998 (Canada) 43 ● n ⫽ 194

● Low risk* with DVT and/or

PE treated as outpatients

● 34 patients had confirmed PE

● Dalteparin (100 U/kg bid or 200 U/kg qd) administered at home for ⱖ5 days

● Warfarin coadministration

● 3-mo follow-up

Recurrent VTE Major hemorrhage Minor hemorrhage Death

3.6% (7/194) 2.0% (4/194) 5.1% (10/194) 7.2% † (14/194)

Small no of patients with PE

Kovacs et al.,

1998 (Canada) 44 ● n ⫽ 108

● Patients with PE treated as outpatients ‡

● Dalteparin (200 U/kg qd) administered

at home for ⱖ5 days

● 3-mo follow-up

Recurrent VTE Major hemorrhage Death

5.6% (6/108) 1.9% (2/108) 3.7% § (4/108)

81 patients were managed exclusively as

outpatients Labas et al.,

2001 (Slovakia) 45 ● n ⫽ 106

● Patients diagnosed with DVT and/or PE

● 28 patients had confirmed PE

● Enoxaparin (1 mg/kg bid) administered for ⱖ7 days

● Elastic compression stockings and recommended mobilization

Death at 8 –12 wk Recurrent VTE at 1-yr follow-up

0 (0/90)

0 (0/46)

● Small no of patients with PE

● Limited details given regarding diagnostic criteria for PE or for outpatient treatment Beer et al.,

2002 (Switzerland) 46 ● n ⫽ 43

● Patients with symptomatic

PE at low predicted risk储

● Nadroparin 171 U/kg administered for 5–10 days

● Warfarin coadministration for 6-12 mo

Recurrent PE Bleeding at 3 mo Death at 3 mo

2.3% (1/43)

0 (0/43)

Small no of patients with PE

Rhodes et al.,

2005 (United

Kingdom) 47

● n ⫽ 107

● Patients with confirmed PE treated as outpatients ¶

● Tinzaparin (175 U/kg qd) for ⱖ6 days

● Warfarin coadministration Significant adverse events

# during the treatment phase

0 (0/93) Outcome data only

available for treatment phase

Olsson et al.,

2006 (Sweden) 48 ● n ⫽ 102

● Patients with symptomatic small or medium-sized PE quantified by V/Q scan**

● Patients had daily visits to outpatient office

● Tinzaparin (175 U/kg qd) for 5–6 days

● Warfarin coadministration for 6 mo

● Clinical symptoms and repeat V/Q scan assessed at day 5 to evaluate recurrent PE

Recurrent PE (new mismatched defects) at late follow-up (4 – 46 mo) Death after 1– 4 mo Required hospitalization

8.5% (5/59)

4% †† (4/100) 5% (5/100)

V/Q scans at late follow-up were only performed in 58% of patients

DVT ⫽ deep vein thrombosis; VTE ⫽ venous thromboembolism; V/Q ⫽ ventilation/perfusion.

*Patients were eligible for outpatient treatment if they had been objectively diagnosed with DVT, unless they had massive pulmonary embolism, high risk for major bleeding or an active bleed, phlegmasia,

or were hospitalized for reasons that prevented discharge 43

† Causes of death included cancer (n ⫽ 11), sepsis (n ⫽ 1), myocardial infarction (n ⫽ 1), and sudden death not attributed to PE (n ⫽ 1).

‡ Patients were eligible for outpatient treatment if they had been objectively diagnosed with PE, and did not meet any of the following criteria: admitted to the hospital for another reason; experienced active bleeding or were at high risk for major bleeding, hemodynamic instability, or pain requiring narcotics; required oxygen therapy; were aged ⬍18 years, or were at risk for poor adherence 44

§ Deaths not attributed to bleeding complications or PE.

储 Based on risk score assessment described by Wicki et al., 2000 16

¶ Patients were eligible for outpatient treatment if they had been objectively diagnosed with PE, and were not at the highest risk for major bleeding (intracerebral bleed within the last 6 months, gastrointestinal bleed in the last month, or verified bleeding disorder) Patients with renal or liver failure, pregnancy, or gross hypertension were evaluated on an individual basis 47

# Significant adverse events included bleeding, thromboembolic complications, and death.

**Patients were excluded if PE was extensive, defined as ⬎7 segments with reduced perfusion (representing ⬎ 40% of the total lung perfusion); had severe, concomitant lung disease such as COPD, pneumonia, and heart failure; had other reason for hospitalization (e.g., recent surgery, bleeding, or severe pain) 48

†† Causes of death included cancer (n ⫽ 11), renal insufficiency (n ⫽ 1), cerebral bleeding (n ⫽ 1), and massive pleural effusion/thoracocentesis (n ⫽ 1).

Adapted from Arch Intern Med,43Thromb Haemost,44Bratisl Lek Listy,45J Thromb Haemost,46Blood,47and Med Sci Monit.48

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during the 3-month follow-up period and major bleeding

and death during the initial treatment period Fondaparinux

was administered as a once-daily subcutaneous dose of 7.5

mg (adjusted to 5 mg and 10 mg for patients weighing⬍50

kg and ⬎100 kg, respectively) Only 42 (3.8%) of 1,103

patients who received fondaparinux had recurrent VTE

events compared with 56 (5.0%) of 1,110 patients assigned

to receive UFH, for an absolute difference of⫺1.2

percent-age points in favor of fondaparinux (P⫽ NS) Major and

nonmajor bleeding, thrombocytopenia, and mortality were

similar in both groups during the entire period of the study

The current ACCP recommendations for SPE involves

admitting all patients to the hospital for administration of

parenteral anticoagulation therapy, either UFH or LMWH,

as a bridge to warfarin with a minimum of 5 days of overlap

until a therapeutic international normalized ratio (INR)

⬎2.0 is achieved.4

Warfarin should be continued for a minimum of 6 to 12 months Fondaparinux was not yet

approved for treatment of DVT and PE when the Seventh

ACCP Conference on Antithrombotic and Thrombolytic

Therapy developed treatment guidelines; therefore, this

op-tion was not included when the guidelines were released in

2004

BENEFITS OF OUTPATIENT TREATMENT

There is growing evidence that AHD and partial

outpa-tient therapy is feasible for paoutpa-tients with nonmassive

SPE.44 – 48,51–57Partial outpatient treatment of PE via an

AHD program may be offered to patients deemed to be at

low risk for mortality, recurrent PE, or major bleeding

complications; who have a home environment with

ade-quate support; and who are able to self-administer the

medications (see Tables 1 and 2 for risk stratification

criteria).53,54 In 1 study, up to 83% of VTE patients

qualified for outpatient treatment.43Benefits of outpatient

management include improved quality-of-life

mea-sures,58 increased physical activity and social

function-ing,58 reduced length of stay,58,59 and substantial cost

savings.52,60,61Pharmacoeconomic analyses of outpatient

treatment for DVT reported cost reductions of 34% to

64%.52 Agnelli and colleagues52 reported ⬎ $2,400 in

cost savings per patient when acute PE was treated on an

outpatient basis However, despite these incentives,

cli-nicians are rightfully disinclined to send home patients

who might be at risk for an unfavorable outcome.16

Several studies have demonstrated successful outpatient

therapy with LMWH as a bridge to warfarin for the

treat-ment of acute SPE (Table 4).43– 48In addition, 158 patients

in the fondaparinux group of the MATISSE-PE trial were

permitted early discharge and received fondaparinux partly

on an outpatient basis51,59; 5 of these patients had recurrent

VTE, and none had major bleeding or died during initial

treatment.59 In light of the current data and the

consider-ation for AHD with partial outpatient therapy of acute PE,

there is a need to accurately predict patient suitability for

this type of therapy It is likely that identification of low-risk

patients with acute PE will facilitate less complex treatment and allow for earlier discharge without sacrificing efficacy

or safety

SUMMARY

Acute PE has a wide clinical spectrum, ranging from asymptomatic patients to those presenting with sudden death The clinical course in patients who survive an initial thromboembolic episode can be complicated by recurrent nonfatal VTE, fatal PE, postthrombotic syndrome, and chronic thromboembolic pulmonary hypertension Early identification of high-risk patients with acute PE who are at increased risk for adverse outcomes remains a challenge in clinical practice A substantial subset of patients with stable

PE may be amenable to outpatient treatment; however, appropriate risk stratification is necessary to identify these candidates Outpatient treatment in these patients can re-duce hospital stay, improve patient quality of life, and decrease healthcare costs Further studies are needed to establish clear clinical pathways that prospectively use con-temporary risk stratification criteria for AHD of patients presenting with acute SPE

Treatment of acute PE with LMWH or fondaparinux administered in an outpatient setting for appropriately se-lected patients is at least as effective and safe as conven-tional inpatient treatment with UFH in preventing recurrent VTE, without increasing the risk for major bleeding when patients are closely monitored Phase 3 clinical trials have shown fondaparinux to be an effective alternative to LMWHs and UFH for the outpatient treatment of DVT62; addition-ally, these trials have shown it to be efficacious in inpatient and partial outpatient treatment of PE.51Fondaparinux cur-rently is the only FDA-approved medication for partial outpatient treatment of SPE

CONFLICT OF INTEREST

These authors report the following conflicts of interest with the sponsor of this supplement article or products discussed

in this article Teresa L Carman, MD, has served as a member of the Speakers’ Bureau for Bristol-Myers Squibb Company Amjad AlMahameed, MD, has served as a mem-ber of the Speakers’ Bureau for sanofi-aventis and Glaxo-SmithKline

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