Enoxaparin monotherapy without oral anticoagulation to treat acute symptomatic pulmonary embolism

SummaryConventional anticoagulation for symptomatic pulmonary embolism consists of continuous intravenous unfractionated heparin as a “bridge” to oral anticoagulation. This strategy requires 5 days or more of intravenous heparin while oral vitamin K antagonists gradually achieve a therapeutic effect. Oral vitamin K antagonists require frequent blood testing to optimize dosing, and their interactions with other medications and foods make regulation difficult. Therefore we tested a different approach to therapy: long-term enoxaparin monotherapy.We randomized 60 symptomatic pulmonary embolism patients in a 2:1 ratio to 90 days of enoxaparin as monotherapy without warfarin (N=40) or to intravenous unfractionated heparin as a “bridge” to warfarin, target INR 2.0-3.0 (N=20). Enoxaparin patients received 1 mg/kg twice daily for 14 days during the acute phase followed by randomized assignment during the chronic phase to 1.0 mg/kg vs. 1.5 mg/kg once daily.In an intention-to-treat analysis, 3 of the 40 enoxaparin patients developed recurrent venous thromboembolism compared with 0 of 20 standard therapy patients (p = 0.54). One of the 40 enoxaparin patients had a major hemorrhagic complication compared with 2 of the 20 standard therapy patients (p = 0.26). Median hospital length of stay was shorter with enoxaparin compared to standard therapy (4 vs. 6 days) (p = 0.001). Following our study we can conclude that extended 3-month treatment with enoxaparin as monotherapy for symptomatic, acute pulmonary embolism is feasible and warrants further study in a large clinical trial.

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Performance Of The Simplified Pesi Score In Patients With Pulmonary Embolism Treated With Rivaroxaban Or Standard Therapy

Blood ◽

10.1182/blood.v122.21.1139.1139 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1139-1139

Author(s):

Petra MG Erkens ◽

Gregory J Fermann ◽

Martin H Prins ◽

Philip S Wells ◽

Akos F Pap ◽

...

Keyword(s):

Pulmonary Embolism ◽

Board Of Directors ◽

Vitamin K ◽

Standard Therapy ◽

Research Funding ◽

Vitamin K Antagonists ◽

Adverse Outcomes ◽

Phase Iii ◽

Advisory Committees ◽

Symptomatic Pulmonary Embolism

Abstract Background The Pulmonary Embolism Severity Index (PESI) has been validated in the setting of standard treatment of pulmonary embolism with initial low molecular weight heparin followed by vitamin K antagonists. We evaluated the proposed simplified PESI in a large, phase III randomized trial involving patients with symptomatic pulmonary embolism with or without deep vein thrombosis, who were treated with rivaroxaban or standard therapy. Methods The EINSTEIN PE study was an open-label, randomized, phase III study that compared oral rivaroxaban alone (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with subcutaneous enoxaparin overlapping with and followed by a vitamin K antagonist (warfarin or acenocoumarol, target international normalized ratio 2.0–3.0) for 3, 6, or 12 months in patients with acute, symptomatic pulmonary embolism. At baseline, the simplified PESI score was assessed, with 1 point each assigned for age >80 years, history of cancer, chronic cardiopulmonary disease, heart beat ≥110 beats per minute, systolic blood pressure <100 mm Hg, and arterial oxyhemoglobin saturation <90%. Recurrent venous thromboembolism, fatal pulmonary embolism, all-cause mortality, and major bleeding at 7 days, 14 days, 30 days, 90 days, and at the end of the full intended treatment period were related to the simplified PESI score. Results It was possible to calculate the simplified PESI score in 4831 of the 4832 included patients, of whom 2589 (53.6%) had a PESI score of 0; 1775 (36.7%) had a score of 1; and 467 (9.7%) had a score of 2 or 3. No patient had a simplified PESI score greater than 3. Incidences of outcomes in relation to time period, simplified PESI score and treatment are presented in the following table. Conclusions Among patients with a simplified PESI score of 0 or 1, major clinical outcome events were rare during the first 30 days of treatment and were similar in patients treated with rivaroxaban or standard therapy. Patients with a simplified PESI score of 2 or more in both treatment groups had more frequent adverse outcomes both initially and in the long term. Disclosures: Fermann: Novartis: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Radiometer: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Cubist: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Cardiorentis: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Prins:Bayer HealthCare: Consultancy; Sanofi-aventis: Consultancy; Boehringer Ingelheim: Consultancy; GlaxoSmithKline: Consultancy; Daiichi Sankyo: Consultancy; Leo Pharma: Consultancy; Thrombogenics: Consultancy; Pfizer: Consultancy. Wells:BMS/Pfizer: Research Funding; Pfizer: Honoraria; Bayer Schering Pharma: Honoraria; Boehringer Ingelheim: Honoraria; Bayer HealthCare Pharmaceuticals: Honoraria; Biomerieux: Honoraria. Pap:Bayer Pharma AG: Employment. Lensing:Bayer Pharma AG: Employment.

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Review of Medical Therapies for the Management of Pulmonary Embolism

Medicina ◽

10.3390/medicina57020110 ◽

2021 ◽

Vol 57 (2) ◽

pp. 110

Author(s):

Ladan Panahi ◽

George Udeani ◽

Michael Horseman ◽

Jaye Weston ◽

Nephy Samuel ◽

...

Keyword(s):

Pulmonary Embolism ◽

Vitamin K ◽

Vitamin K Antagonists ◽

Toxicity Profile ◽

Oral Vitamin ◽

Pharmacological Management ◽

Reversal Agents ◽

Outpatient Settings ◽

Oral Therapeutic ◽

Selection Of

Traditionally, the management of patients with pulmonary embolism has been accomplished with anticoagulant treatment with parenteral heparins and oral vitamin K antagonists. Although the administration of heparins and oral vitamin K antagonists still plays a role in pulmonary embolism management, the use of these therapies are limited due to other options now available. This is due to their toxicity profile, clearance limitations, and many interactions with other medications and nutrients. The emergence of direct oral anticoagulation therapies has led to more options now being available to manage pulmonary embolism in inpatient and outpatient settings conveniently. These oral therapeutic options have opened up opportunities for safe and effective pulmonary embolism management, as more evidence and research is now available about reversal agents and monitoring parameters. The evolution of the pharmacological management of pulmonary embolism has provided us with better understanding regarding the selection of anticoagulants. There is also a better understanding and employment of anticoagulants in pulmonary embolism in special populations, such as patients with liver failure, renal failure, malignancy, and COVID-19.

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Anticoagulants in the Management of Pulmonary Embolism

10.5772/intechopen.100471 ◽

2021 ◽

Author(s):

Ladan Panahi ◽

George Udeani ◽

Michael Horseman ◽

Jaye Weston ◽

Nephy Samuel ◽

...

Keyword(s):

Pulmonary Embolism ◽

Vitamin K ◽

Vitamin K Antagonists ◽

Toxicity Profile ◽

Oral Vitamin ◽

Pharmacological Management ◽

Reversal Agents ◽

Outpatient Settings ◽

Selection Of

Pulmonary embolism management has typically been accomplished with anticoagulant treatment that includes parenteral heparins and oral vitamin K antagonists. Even though heparins and oral vitamin K antagonists continue to play a role in pulmonary embolism management, other newer available options have somewhat reduced the role of heparins and vitamin K antagonists in pulmonary embolism management. This reduction in utilization involves their toxicity profile, clearance limitations, and many drug and nutrient interactions. New direct oral anticoagulation therapies have led to more available options in the management of pulmonary embolism in the inpatient and outpatient settings. More evidence and research are now available about reversal agents and monitoring parameters regarding these newer agents, leading to more interest in administering them for safe and effective pulmonary embolism management. Current research and literature have also helped direct the selection of appropriate use of pharmacological management of pulmonary embolism based on the specific population such as patients with liver failure, renal failure, malignancy, and COVID-19.

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Spectrophotometric Assays of Prothrombin in Plasma of Patients Using Oral Anticoagulants

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657025 ◽

1979 ◽

Vol 42 (04) ◽

pp. 1296-1305 ◽

Cited By ~ 29

Author(s):

R M Bertina ◽

W van der Marel-van Nieuwkoop ◽

E A Loeliger

Keyword(s):

Prothrombin Time ◽

Vitamin K ◽

Oral Anticoagulation ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Factor Xa ◽

Factor V ◽

Anticoagulant Treatment ◽

Factor Ii ◽

K Deficiency

SummaryTwo spectrophotometric assays for prothrombin have been developed and compared with a one stage coagulant and an immunological assay. One of these assays (called the XAPC assay) uses a combination of factor Xa, phospholipid, Ca2+ and factor V as activator of prothrombin, and measures only normal prothrombin. The second (the ECAR assay) uses Echis carinatus venom as activator. This assay measures both normal prothrombin and PIVKA II (protein induced by vitamin K antagonists/absence). Combination of the results obtained by the XAPC and ECAR assays provides rapid and reliable information on the degree of “subcarboxylation” of prothrombin (oral anticoagulation, vitamin K deficiency).For patients on long term anticoagulant treatment the prothrombin time (Thrombotest) shows better correlation with the ratio prothrombin/prothrombin plus PIVKA II (XAPC/ ECAR) than with the factor II concentration. For patients starting the anticoagulant treatment there is no correlation between the Thrombotest time and the XAPC/ECAR ratio.It seems doubtful that (a) spectrophotometric factor II assay(s) will be as useful as the prothrombin time in the control of oral anticoagulation.

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Inferior Vena Cava Agenesis and Deep Vein Thrombosis: A Pharmacological Alternative to Vitamin K Antagonists

European Journal of Case Reports in Internal Medicine ◽

10.12890/2019_001310 ◽

2019 ◽

Author(s):

Inês Esteves Cruz ◽

Pedro Ferreira ◽

Raquel Silva ◽

Francisco Silva ◽

Isabel Madruga

Keyword(s):

Deep Vein Thrombosis ◽

Inferior Vena Cava ◽

Vitamin K ◽

Oral Anticoagulation ◽

Inferior Vena ◽

Vitamin K Antagonists ◽

Anticoagulation Therapy ◽

Vena Cava ◽

Vein Thrombosis ◽

Deep Vein

Inferior vena cava (IVC) agenesis is a rare congenital abnormality affecting the infrarenal segment, the suprarenal or the whole of the IVC. It has an estimated prevalence of up to 1% in the general population that can rise to 8.7% when abnormalities of the left renal vein are considered. Most IVC malformations are asymptomatic but may be associated with nonspecific symptoms or present as deep vein thrombosis (DVT). Up to 5% of young individuals under 30 years of age with unprovoked DVT are found to have this condition. Regarding the treatment of IVC agenesis-associated DVT, there are no standard guidelines. Treatment is directed towards preventing thrombosis or its recurrence. Low molecular weight heparin and oral anticoagulation medication, in particular vitamin K antagonists (VKAs) are the mainstay of therapy. Given the high risk of DVT recurrence in these patients, oral anticoagulation therapy is suggested to be pursued indefinitely. As far as we know, this is the first case reporting the use of a direct factor Xa inhibitor in IVC agenesis-associated DVT. Given VKA monitoring limitations, the use of a direct Xa inhibitor could be an alternative in young individuals with anatomical defects without thrombophilia, but further studies will be needed to confirm its efficacy and safety.

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Management of pulmonary embolism in patients with cancer

ESC CardioMed ◽

10.1093/med/9780198784906.003.0666 ◽

2018 ◽

pp. 2790-2794

Author(s):

Cihan Ay ◽

Florian Posch

Keyword(s):

Pulmonary Embolism ◽

Vitamin K ◽

Meta Analysis ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Standard Of Care ◽

Current Standard ◽

Patients With Cancer ◽

High Index Of Suspicion ◽

Excessive Anticoagulation

Pulmonary embolism (PE) is a frequent complication in patients with cancer. Clinicians have to maintain a high index of suspicion to reduce the large proportion of PEs that remain undiagnosed in the cancer population. Thrombolysis is not a standard treatment for haemodynamically unstable patients with cancer-associated PE because the risk of haemorrhage can be excessive. Anticoagulation with a low-molecular-weight heparin (LMWH) for at least 6 months is the current standard of care for the treatment of cancer-associated PE, while vitamin K antagonists are a reasonable second choice for patients with contraindications against LMWH or a strong preference towards an oral agent. Although an indirect network meta-analysis suggests that non-vitamin K-dependent oral anticoagulants may be comparably efficacious and safe as LMWH for treating PE in cancer patients, these agents cannot be recommended as a standard first-line treatment at this time because a head-to-head comparison to the standard of care has not yet been reported. Anticoagulation beyond 6 months is an emerging concept; however, the patient population that may benefit from this intervention still needs to be defined. Guidance statements facilitate the management of challenging patients with brain metastases, unsuspected PE, thrombocytopenia, and recurrent PE.

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4037Nurse counseling of patients with atrial fibrillation to improve compliance to oral anticoagulation

European Heart Journal ◽

10.1093/eurheartj/ehz745.0092 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

R Chilian-Hof ◽

S Schnupp ◽

C Mahnkopf ◽

J Brachmann ◽

C Kleinecke

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Oral Anticoagulation ◽

Vitamin K Antagonists ◽

Randomised Trial ◽

Female Gender ◽

Bleeding Risk ◽

Telephone Counseling ◽

Bleeding Events

Abstract Background Atrial fibrillation (AF) is the most frequent arrhythmia with a prevalence of 1%–2% in the general population. Oral anticoagulation (OAC) is state-of-the art for preventions of thromboembolic events, in particular ischemic stroke, in patients with atrial fibrillation. Despite its proven benefit, numerous studies have documented under use of OAC for a variety of reasons. Purpose To establish a program of nurse counseling in patient with atrial fibrillation and treatment with oral anticoagulation. The program is designed to improve patients satisfaction, compliance to OAC, prevention of medication errors, ischemic and bleeding events. Methods Patients with atrial fibrillation and treatment with oral anticoagulation were prospectively identified at the department of cardiology of our clinic. They received a 30 minutes nurse counseling about oral anticoagulation during the hospital stay and another 30 minutes telephone counseling 3 months after inclusion. Furthermore, they received a brochure to inform about atrial fibrillation, oral anticoagulation and methods to improve medication compliance. Demographic characteristics with stroke and bleeding risk (CHA2DS2-VASc and HAS-BLED scores), as well as procedural data were systematically assessed in a predefined standardized way and captured in a dedicated database. Results Between June 2017 and January 2018, a total of 617 patients (female gender: 43.1%) with atrial fibrillation and oral anticoagulation received nurse counseling. Demographic and follow-up data of 204 patients (female gender: 85/204 (41.7%); mean age 69.7±17.3, CHA2DS2-VASc score 4.2±1.7, HAS-BLED score 2.8±0.37) were assessed in a dedicated database. Indication for OAC was paroxysmal and persistent/permanent AF in 110/204 (53.9%), 93/204 (45.6%) and others 17 (8.3%), respectively. 33/2014 (16.2%) were treated with vitamin K antagonists, and 172/204 (84.3%) with non-vitamin K antagonists. After a follow-up of 0.46±2.9 years and 187 patients-years the rates of cardiovascular death, major bleeding events and all-cause stroke and TIA were 1.07%, 2.14% and 1.61% per 100 patient-years. Conclusion Nurse counseling in patients with atrial fibrillation and treatment with oral anticoagulation has been established at the REGIOMED clinics, Germany. Its effectiveness in terms of quality of live, medication complications and cardiovascular events has to be proven in a randomised trial. Acknowledgement/Funding Daichi-Sankyo

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