Extended duration of thromboprophylaxis in acutely ill medical patients: optimizing therapy?

Abstract Introduction In the EXCLAIM study, extended-duration enoxaparin prophylaxis reduced the relative risk of VTE in acutely ill medical patients by 44% compared with placebo, following standard-duration prophylaxis (2.8% vs 4.9%; RR 0.56; 95% CI 0.39–0.80; p=0.0011). We assessed the benefits of extended-duration enoxaparin prophylaxis in subgroups of acutely ill medical patients with the most prominent primary diagnoses enrolled in EXCLAIM. Methods Patients enrolled in EXCLAIM had: recent reduced mobility (≤3 days) due to a medical illness, age ≥40 years, and anticipated level 1 (total bed rest or sedentary without bathroom privileges) or level 2 (level 1 with bathroom privileges) reduced mobility with further risk factors. Eligible patients received enoxaparin 40mg SC once-daily for 10±4 days, and were then double-blind randomized and received enoxaparin 40mg SC once-daily (n=2013) or placebo (n=2027) for a further 28±4 days. Asymptomatic DVT were diagnosed by bilateral compression ultrasound after completion of the randomized treatment. Suspected cases of symptomatic DVT or PE were confirmed by objective tests. Fatal PE were confirmed by autopsy where possible. Univariate logistic regressions were conducted to estimate treatment effects in patient subgroups. The primary safety endpoint was major bleeding. Results Baseline characteristics were similar between treatments within each primary diagnosis subgroup, and the considered primary diagnoses accounted for >80% of the enrolled population. The reduced VTE incidence associated with extended-duration enoxaparin prophylaxis was consistent across subgroups of patients with different primary diagnoses (Table). The incidence of major bleeding was generally higher in patients receiving extended-duration prophylaxis (Table). Table: VTE and major bleeding in patient subgroups receiving extended-duration vs standard-duration prophylaxis/placebo Primary diagnosis Incidence of VTE (%)* Odds Ratio [95% CI]** Incidence of Major Bleeding (%)*** Odds Ratio [95% CI] Extended Enox Standard Enox/Placebo Extended Enox Standard Enox/Placebo *N=3347 evaluable patients; **Alpha adjustment for an interim analysis; ***N=4040 treated patients Heart failure, NYHA class III or IV 3.1 4.7 0.64 [0.29–1.39] 0.0 0.2 N/A Acute respiratory insufficiency 2.2 3.7 0.60 [0.27–1.34] 0.6 0.2 3.15 [0.33–30.4] Post ischemic stroke 2.1 8.3 0.24 [0.06–0.91] 0.6 0.0 N/A Acute infection without septic shock 3.6 5.3 0.66 [0.36–1.22] 0.8 0.2 5.16 [0.60–44.3] Conclusion Extended enoxaparin prophylaxis consistently reduced VTE risk in acutely ill medical patients with the most prominent primary diagnoses compared with placebo following standard-duration prophylaxis. Major bleeding was generally higher in the extended-duration enoxaparin arm, but rates of bleeding were low. These findings are consistent with the primary findings of the EXCLAIM study which demonstrated the clinical benefit of the extended-duration enoxaparin regimen.

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Extended-Duration Venous Thromboembolism Prophylaxis for Medical Patients

Annals of Internal Medicine ◽

10.7326/0003-4819-153-10-201011160-00020 ◽

2010 ◽

Vol 153 (10) ◽

pp. 689

Author(s):

Michael P. Carson ◽

Yen-Hong Kuo

Keyword(s):

Venous Thromboembolism ◽

Medical Patients ◽

Thromboembolism Prophylaxis ◽

Venous Thromboembolism Prophylaxis ◽

Extended Duration

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Extended-Duration Venous Thromboembolism Prophylaxis for Medical Patients

Annals of Internal Medicine ◽

10.7326/0003-4819-153-10-201011160-00019 ◽

2010 ◽

Vol 153 (10) ◽

pp. 688

Author(s):

Jose A. Nieto ◽

Reina Valle ◽

Juan B. Lopez-Saez

Keyword(s):

Venous Thromboembolism ◽

Medical Patients ◽

Thromboembolism Prophylaxis ◽

Venous Thromboembolism Prophylaxis ◽

Extended Duration

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Extended-Duration Use of Direct Oral Anticoagulants to Prevent VTE in Acutely III Medical Patients

The Senior Care Pharmacist ◽

10.4140/tcp.n.2019.99 ◽

2019 ◽

Vol 34 (2) ◽

pp. 99-108

Author(s):

Jessica W. Skelley ◽

Angela R. Thomason ◽

Lauren N. Hammond

Keyword(s):

Clinical Trials ◽

Human Subjects ◽

Data Extraction ◽

Oral Anticoagulants ◽

Adult Population ◽

Direct Oral Anticoagulants ◽

Bleeding Risk ◽

Medical Patients ◽

Bleeding Events ◽

Extended Duration

OBJECTIVE: To evaluate current clinical evidence for the use of direct oral anticoagulants (DOACs) for extended-duration thromboprophylaxis in the acutely ill medical population for venous thromboembolism (VTE) and bleeding events.<br/> DATA SOURCES: Were obtained through a MEDLINE/PubMed search for clinical trials conducted from March 2008 to 2018 using relevant key words. Limitations of English and human subjects were applied to search results.<br/> STUDY SELECTION AND DATA EXTRACTION: Forty-one articles were identified, and abstracts reviewed by the authors for inclusion of the study population (acutely ill medical patients) and VTE outcomes. Clinical studies evaluating the use of DOACs for extended duration of VTE prevention in acutely ill medical patients were included in the review, resulting in three clinical trials and two subgroup analyses. The participants enrolled had an overall mean age of 71.4 years.<br/> DATA SYNTHESIS: The DOAC trials collectively demonstrated a positive outcome in composite endpoints of VTE prevention with extended-duration thromboprophylaxis in acutely ill medical patients compared with enoxaparin. As for safety, rivaroxaban and apixaban trials reported more major bleeding events compared with enoxaparin. The betrixaban trial demonstrated no difference in bleeding compared with enoxaparin.<br/> CONCLUSION: DOACs reduced the number of VTE events in acutely ill medical patients on extended-duration thromboprophylaxis, but with an overall increased bleeding risk. An individualized patient approach based on risk factors should be utilized for treatment with extended-duration DOAC in the older adult population with recent hospitalization.

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Extended-Duration Enoxaparin for Venous Thromboembolism Prophylaxis in Acutely Ill Medical Patients: An Evaluation of the EXCLAIM Study Based on a Recently Recommended Composite Efficacy Endpoint.

Blood ◽

10.1182/blood.v110.11.1870.1870 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1870-1870 ◽

Cited By ~ 1

Author(s):

Sebastian M. Schellong ◽

Russell D. Hull ◽

Victor F. Tapson ◽

Manuel Monreal ◽

Meyer-Michel Samama ◽

...

Keyword(s):

Venous Thromboembolism ◽

Composite Endpoint ◽

Medical Patients ◽

Double Blind ◽

Once Daily ◽

All Cause Mortality ◽

Standard Duration ◽

Extended Duration ◽

Level 1 ◽

Reduced Mobility

Abstract Introduction The EXCLAIM study has shown that in acutely ill medical patients who have received a standard 10-day period of prophylaxis with enoxaparin, extended-duration prophylaxis with enoxaparin for 4 weeks reduces the relative risk of the primary composite endpoint of asymptomatic proximal deep-vein thrombosis (DVT), symptomatic DVT or pulmonary embolism (PE), and fatal PE by 44% compared with placebo (2.8% vs 4.9%; RR 0.56; 95% CI 0.39–0.80; p=0.0011). We assessed the consistency of these results using the composite efficacy endpoint recently proposed for venous thromboembolism (VTE) prophylaxis studies by the European Committee for Medicinal Products for Human Use (CHMP) which, in addition, takes all-cause mortality into account. Methods Patients enrolled in the EXCLAIM study had a recent reduced mobility (≤3 days) due to a medical illness, were aged 40 years or older, and had anticipated level 1 (total bed rest or sedentary without bathroom privileges) or level 2 (level 1 with bathroom privileges) reduced mobility with further risk factors. Eligible patients received enoxaparin 40mg SC once-daily for 10±4 days. Patients were then double-blind randomized and received either enoxaparin 40mg SC once-daily or placebo for a further 28±4 days. Asymptomatic DVT were diagnosed by bilateral compression ultrasound after completion of the randomized treatment period. Suspected cases of symptomatic DVT or PE were confirmed by objective tests. Fatal PE were confirmed by autopsy where possible. Data were analyzed using the CHMP-recommended composite efficacy endpoint of proximal DVT, adjudicated PE and all-cause mortality. Results Eligible patients enrolled at 370 sites in 20 countries received standard-duration prophylaxis with enoxaparin. Of these, 4114 patients were double-blind randomized and 4040 received extended-duration prophylaxis with enoxaparin (n=2013) and placebo (n=2027), respectively. Extended-duration enoxaparin reduced the relative risk of the CHMP composite endpoint by 26% compared with placebo (5.8% vs 7.9%; RR 0.74; 95% CI 0.58–0.95; p=0.018). Conclusion The significant reduction in the incidence of the primary efficacy endpoint associated with the use of extended-duration enoxaparin compared with placebo, following standard duration enoxaparin, was consistent when applying both the pre-defined EXCLAIM and the CHMP-recommended composite endpoints, the latter of which included all-cause mortality in addition to proximal DVT and adjudicated PE.

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The Role of Low Molecular Weight Heparins for Venous Thromboembolism Prevention in Medical Patients—What Is New in 2019?

Hämostaseologie ◽

10.1055/s-0038-1677522 ◽

2019 ◽

Vol 39 (01) ◽

pp. 062-066 ◽

Cited By ~ 4

Author(s):

Sylvia Haas

Keyword(s):

Molecular Weight ◽

Venous Thromboembolism ◽

Randomized Clinical Trials ◽

Scientific Evidence ◽

Oral Anticoagulants ◽

Low Molecular Weight ◽

Medical Patients ◽

Low Molecular Weight Heparins ◽

Venous Thromboembolism Prevention ◽

Extended Duration

AbstractLow molecular weight heparins and fondaparinux have been the cornerstones for prevention of venous thromboembolism (VTE) in acutely ill medical patients for almost two decades. Guidelines recommend the use of these parenteral anticoagulants for 6 to 14 days but advise against extended-duration thromboprophylaxis after hospital discharge because no compelling scientific evidence has been provided for pharmacological prophylaxis beyond hospital stay. Five large randomized clinical trials, one with low molecular weight heparin and four with nonvitamin K antagonist oral anticoagulants, have failed to show significant clinically relevant benefit in this indication. Obviously, the development of VTE is more complex in medical patients than in patients undergoing major surgical procedures. Thus, it can be expected that guideline recommendations for VTE prevention with low molecular weight heparins or fondaparinux in medical patients will remain unchanged in 2019.

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