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Supplements Extended Prophylaxis for Venous Thromboembolism in Acute Medically Ill Patients
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Venous Thromboembolism in Acute Medically Ill Patients: Identifying Unmet Needs and Weighing the Value of Prophylaxis
Paul P. Dobesh, PharmD; Tania Ahuja, PharmD; George A. Davis, PharmD; Hugh Fatodu, MBA, RPh; William H. Francis, MBA, RPh; Frank P. Hull, MD; Gary L. Johnson, MD, MS, MBA; Joshua D. Lenchus, DO, BSPharm; Jacqueline Glee Lenoir, PharmD; Claudette McPherson, RN, BSN; Jeffrey Nemeth, PharmD, MPA; and Ralph J. Riello III, PharmD
Best Practices for Implementing Venous Thromboembolism Prophylaxis Across the Continuum of Care
Paul P. Dobesh, PharmD; Tania Ahuja, PharmD; George A. Davis, PharmD; Hugh Fatodu, MBA, RPh; William H. Francis, MBA, RPh; Frank P. Hull, MD; Gary L. Johnson, MD, MS, MBA; Joshua D. Lenchus, DO, BSPharm; Jacqueline Glee Lenoir, PharmD; Claudette McPherson, RN, BSN; Jeffrey Nemeth, PharmD, MPA; and Ralph J. Riello III, PharmD
Participating Faculty

Venous Thromboembolism in Acute Medically Ill Patients: Identifying Unmet Needs and Weighing the Value of Prophylaxis

Paul P. Dobesh, PharmD; Tania Ahuja, PharmD; George A. Davis, PharmD; Hugh Fatodu, MBA, RPh; William H. Francis, MBA, RPh; Frank P. Hull, MD; Gary L. Johnson, MD, MS, MBA; Joshua D. Lenchus, DO, BSPharm; Jacqueline Glee Lenoir, PharmD; Claudette McPherson, RN, BSN; Jeffrey Nemeth, PharmD, MPA; and Ralph J. Riello III, PharmD
  • Over 8 million acute medically ill patients each year in the United States are at risk for experiencing venous thromboembolism (VTE) events, with up to 900,000 patients developing blood clots for the first time.
  • Patients who are hospitalized for acute medical illnesses (eg, pneumonia, stroke particularly ischemic stroke, and heart failure) have more than a 10-fold increased risk of developing VTE events compared to those who are not hospitalized.
  • In acute medically ill patients, the risk of experiencing VTE events remains high after hospitalization, especially within the first 30 days post discharge.
  • Up to 200,000 VTE-related events occur despite prophylaxis, with an estimated 40,000 deaths directly or indirectly related to VTE.
  • In total, VTE events cost the US healthcare system $7 billion to
  • $10 billion each year for newly diagnosed, medically-treated incident cases.
  • Inpatient VTE prophylaxis rates are low, ranging from 30% to 60%; postdischarge (extended) prophylaxis rates are even lower, below 10%, typically because no approved extended regimens were available until recently.
  • To date, several clinical trials have evaluated the use of extended-duration VTE prophylaxis with enoxaparin, apixaban, rivaroxaban, and betrixaban compared with standard-duration VTE prophylaxis with enoxaparin. At the current time, betrixaban is the only anticoagulant that has demonstrated clinical benefit and has been FDA-approved for postdischarge extended VTE prophylaxis in acute medically ill patients.
  • An unmet medical need exists for improving the quality of VTE prophylaxis during hospitalization and after discharge in acute medically ill patients, decreasing thromboembolic disease burden and improving long-term patient outcomes.
Am J Manag Care. 2018;24:-S0
Venous thromboembolism (VTE) events, which manifest as deep vein thrombosis (DVT) and/or pulmonary embolism (PE), cause considerable mortality and morbidity.1 As many as 900,000 Americans each year experience VTE events, and as many as 150,000 to 200,000 deaths may be directly or indirectly related to VTE events.2-4 DVTs, which manifest as clots in the deep veins of the body, are the most common form of VTE event; approximately two-thirds of VTE events are characterized as DVTs.5 The most serious complication that can result from DVTs are PEs, and they occur in approximately one-third of patients with DVTs.2,5 PEs, which develop when a portion of the DVT breaks off and enters the pulmonary arteries, account for 5% to 10% of US inpatient deaths annually.6  

Risk factors for VTE events can be genetic, acquired, or transiently acquired (Table).5,7-9 Using risk assessment models, several prediction scores have been proposed and implemented in clinical practice to stratify VTE risks in hospitalized patients.6 The risk factors adopt weighted variables, such as hospitalization for medical illness; advanced age; past history of VTE or cancer; and reduced mobility commonly are considered key predictors for VTE. Additionally, subacute illnesses, inherited or acquired coagulation disorders, surgery, trauma, infection, obesity, estrogen therapy, or erythropoiesis-stimulating agents may also put patients at risk of VTE.6-8

VTE Events in Acute Medically Ill Patients

Hospitalization is considered the single most important risk factor for developing VTE events.2 As broadly illustrated in Figure 1, patients who are hospitalized for acute medical illnesses such as pneumonia, acute respiratory failure, stroke, or heart failure have more than a tenfold increased risk of developing VTE events.10-13

In fact, 60% to 70% of all VTE events are reported in acute medically ill hospitalized patients, whereas the remainder are found in surgical patients.1 Over 8 million acute medically ill patients each year in the United States are at risk for experiencing VTE events.11 The risk of developing VTE continues beyond hospitalization, especially for the first 30 days after discharge.14 Real-world data suggest that 4.8 million to 5.2 million patients may have an extended VTE risk. 1,6,10,12,13

Stakeholders concurred that the occurrence of VTE events is a significant public health concern. According to Ralph J. Riello III, PharmD, “It is a problem often that hospitals do not know that they have or that exists.” Moreover, George A. Davis, PharmD, observed, “we need to change the way we think about this problem by first thinking about it as a problem.”

Clinical and Economic Burden of VTE Events

The risk of developing primary and/or recurrent VTE events remains high after hospitalization.14 Serious complications, including death, can occur after VTE events. Joshua D. Lenchus, DO, BSPharm, observed that patients are at increased risk of recurrent thromboembolism and chronic morbidity (eg, venous insufficiency and pulmonary hypertension) following VTE events. Further, he noted that recurrence can also be high “following a standard course of anticoagulant therapy; approximately 33% of patients experience a recurrence within 10 years of the initial event, with the highest risk occurring during the first year.” Regarding recurrent events, stakeholders discussed that the Centers for Medicaid and Medicare Services (CMS) sometimes penalize facilities when patients present with recurrent VTE events within the first 30 days of hospital discharge.

In the experience of Riello, typical recurrence is usually within 3 months of the first episode. He noted, “Many hospitals are not aware of their recurrent VTE rates.” He suggested that 2 forms of education are needed: clinicians need to be educated about the risks, and patients need to be taught that the risk for VTE events does not stop once they leave the hospital. One study noted a 34% decrease in patient refusal (44% to 29%) when patients are educated adequately about the rationale for VTE prophylaxis.15 Gary L. Johnson, MD, MS, MBA, encouraged providers/prescribers to openly discuss the need for thromboprophylaxis with patients and allow them to have “shared decision making” regarding treatment options.

An estimated 10% to 30% of patients suffer mortality within 30 days of experiencing a VTE event, with most deaths being related to PE events.5 Some patients who initially survive a VTE event die within 90 days of hospital discharge.16 Stakeholders noted that VTE events are the leading cause of preventable hospital deaths in the United States and agreed that prevention is paramount. In fact, up to 70% of hospital acquired VTE events are preventable (60% of healthcare associated VTE could have been prevented by universal VTE prophylaxis).17

VTE events are not only a major cause of morbidity and mortality in the US, but they also negatively affect quality of life (QOL).5,18 “The QOL impact on these patients is significant,” noted Lenchus. “We discharge them from the hospital, and then we give them drug X. There is a tremendous impact in terms of QOL,” he said. According to the stakeholders, QOL can be impaired in physical, social, and psychological domains.

Compared with population norms in a general US population adjusted for age and sex, Van Korlaar et al found that patients experiencing VTE events scored significantly lower (P <.05) on all subscales of the Short-Form-36 (SF-36), a disease-specific venous thrombosis-quality of life (VT-QOL) questionnaire about the problems faced by patients with venous thrombosis.18 Lenchus observed that QOL decreases, following DVT events. Likewise, the occurrence of postthrombotic syndrome, which may affect 50% of those who have experienced a venous thrombosis, further negatively affects QOL and is associated with decreased activities of daily living and increased pain.5,18,19 Lenchus explained that “33% to 55% of lower-extremity DVT patients develop postthrombotic syndrome and chronic venous insufficiency, which is characterized by pain, swelling, skin necrosis, and ulcerations.”

VTE events are also associated with a substantial societal economic burden, similar to that of myocardial infarction (MI) or stroke.20 In total, VTE events cost the US healthcare system at least $7 billion to $10 billion each year for newly diagnosed, medically treated incident cases; estimated annual healthcare costs for incident and recurrent cases of DVT or PE range from $7594 to $16,644 per patient.21 These figures do not include penalties that may be imposed by CMS for facilities with recurrent VTE events within 30 days of hospital discharge.

Thromboprophylaxis

Although anticoagulant therapy has been used since the approval of warfarin in 1954, the VTE prophylaxis landscape has expanded significantly over the past 25 years with the approval of several new agents, including low molecular weight heparins and, more recently, direct oral anticoagulants.22 With the surge of new medications entering the market, clinicians are challenged with not only interpreting the new drug data, but also applying new or updated guidelines and treatment strategies. These complexities have contributed to suboptimal provider adherence to thromboembolic treatment and prevention strategies.22

In-Hospital Prophylaxis. The benefits of anticoagulant-based thromboprophylaxis (using standard-duration VTE prophylaxis with enoxaparin for 6-14 days) in hospitalized patients at risk for developing VTE events is well established.1 A meta-analysis from 9 clinical trials representing almost 20,000 patients found that thromboprophylaxis significantly decreased the rates of PEs, fatal PEs, and symptomatic DVTs.23 Additionally, significant increases in major bleeding were not observed with thromboprophylaxis compared with no treatment. Despite the benefits, thromboprophylaxis is underutilized. Registry data show that only 40% to 60% of eligible hospitalized patients receive VTE prophylaxis.1 According to the stakeholders, several reasons exist for underutilization of in-hospital VTE prophylaxis, such as decreasing hospitalization length of stay, underestimating the risk of VTE, and concerns regarding bleeding risks.24 Rates of symptomatic VTE events in real-world studies range from 1% to 4% among at-risk acute medically ill patients, and the majority of VTE events occurred after hospital discharge (Figure 2).14,25-29  Additionally, as hospital stay durations are shortening, many patients do not receive the full 6 to 14 days indicated by the guidelines.

Extended-Duration Thromboprophylaxis

In the major trials supporting VTE prophylaxis in acute medically ill patients, the duration of thromboprophylaxis was 6 to 14 days.1 Data suggests that this duration of treatment may not be sufficient for acutely ill medical patients, because the risk of experiencing VTE events remains high for the first 30 days after hospital discharge.14,29-31

One possible reason may be that acute medically ill patients require longer duration thromboprophylaxis because they do not resume their previous level of mobility immediately following discharge from inpatient hospital settings.1

Another study assessed the incidence and time course of symptomatic VTE following hospitalization for medical illness. In this real-world analysis, the cumulative VTE risk over 180 days was calculated. Mean hospital length of stay was 5.3 days, and the majority of VTE events (57%) occurred after hospital discharge and standard prophylaxis completion.14 Less than 10% of patients in this analysis received pharmacological VTE prophylaxis post discharge.14

Several clinical trials have evaluated the efficacy and safety of extended-duration thromboprophylaxis in acute medically ill patients (Figure 3).32-37

 
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