Evolving use of new oral anticoagulants for treatment of venous thromboembolism

Yeh, Calvin H.; Gross, Peter L.; Weitz, Jeffrey I.

doi:10.1182/blood-2014-03-563056

Cited by 120 publications

(104 citation statements)

References 45 publications

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“…The non-vitamin K antagonist oral anticoagulants (NOAC) have the potential to allow patients to be treated by monotherapy from acute to chronic phase, which is a long-awaited treatment option; and to replace conventional therapy for VTE. 5 Apixaban is an orally administered reversible inhibitor that binds to blood coagulation activated factor X (FXa). 5 AMPLIFY, a multi-regional, randomized, double-blind, active-controlled study in which Japanese subjects were not included, showed that a fixed-dose regimen of oral apixaban alone was as effective as conventional treatment consisting of enoxaparin followed by warfarin, and was associated with a clinically relevant reduction of 69% in major bleeding, indicating that apixaban can provide a simple, effective, and safe regimen for the initial and long-term treatment of VTE.…”

Section: Discussionmentioning

confidence: 99%

“…5 Apixaban is an orally administered reversible inhibitor that binds to blood coagulation activated factor X (FXa). 5 AMPLIFY, a multi-regional, randomized, double-blind, active-controlled study in which Japanese subjects were not included, showed that a fixed-dose regimen of oral apixaban alone was as effective as conventional treatment consisting of enoxaparin followed by warfarin, and was associated with a clinically relevant reduction of 69% in major bleeding, indicating that apixaban can provide a simple, effective, and safe regimen for the initial and long-term treatment of VTE. 6 Moreover, it would be of great interest to determine the health economics of NOAC for VTE, and several reports including from The National Institute for Health and Care Excellence indicated that apixaban could be considered a clinically and cost-effective option for VTE.…”

Section: Discussionmentioning

confidence: 99%

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Apixaban for the Treatment of Japanese Subjects With Acute Venous Thromboembolism (AMPLIFY-J Study)

Nakamura

Nishikawa

Komuro

et al. 2015

Circ J

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Background: Anticoagulation is recommended as standard of care for venous thromboembolism (VTE) (pulmonary embolism [PE]/deep vein thrombosis [DVT]), for which unfractionated heparin (UFH) and warfarin are used in Japan. In the multi-regional AMPLIFY study, a fixed-dose regimen of apixaban alone was non-inferior to conventional therapy for treatment of PE/DVT and was associated with significantly fewer bleeding events. Methods and Results:Japan phase 3 study (AMPLIFY-J), randomized, active-controlled, open-label study in Japanese subjects with acute PE/DVT, was designed based on AMPLIFY. Key objectives were to investigate safety and efficacy of apixaban in symptomatic PE/DVT subjects during 24-week treatment. UFH/warfarin was used as control treatment. Apixaban was initiated at 10 mg twice daily for 7 days, followed by 5 mg twice daily for 23 weeks. All endpoints and imaging for thrombotic burden were assessed by an event adjudication committee. Eighty subjects were randomized, 33 subjects (41.3%) were aged <65 years. Proportion of major/clinically relevant non-major bleeding was lower in apixaban (7.5%) compared with well-controlled UFH/warfarin (28.2%; median TTR, 70.1%). Recurrent VTE occurred in no subjects in apixaban and in 1 subject in UFH/warfarin. Thrombotic burden results were similar in both groups. Proportions of subjects with adverse events was generally similar in both groups. Conclusions:Apixaban was well-tolerated and had a favorable safety profile. No clinically important efficacy difference compared with UFH/warfarin was observed. (Circ J 2015; 79: 1230 -1236

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Apixaban for the Treatment of Japanese Subjects With Acute Venous Thromboembolism (AMPLIFY-J Study)

Nakamura

Nishikawa

Komuro

et al. 2015

Circ J

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“…In summary, the RE-LY trial showed that compared with Warfarin the oral direct thrombin inhibitor, Dabigatran etexilate given at a dose of 150 mg twice daily reduces stroke with less intracranial bleeding, and Dabigatran 110 mg twice daily has similar efficacy with less bleeding [19]. The rate of major bleeding was 3.36% per year in the Warfarin group, as compared with 2.71% per year in the group that received 110 mg of Dabigatran (relative risk with Dabigatran, 0.80; 95% CI, 0.69 to 0.93; P = 0.003) and 3.11% per year in the group that received 150 mg of Dabigatran [19].Despite this better performance of dabigatran than warfarin in the bleeding scenario, there are still various emergent situations where the presence of Dabigatran in the blood system may worsen the hemorrhagic event [22][23][24]. Serious bleeding can occur.…”

mentioning

confidence: 96%

“…Despite this better performance of dabigatran than warfarin in the bleeding scenario, there are still various emergent situations where the presence of Dabigatran in the blood system may worsen the hemorrhagic event [22][23][24]. Serious bleeding can occur.…”

mentioning

confidence: 99%

Idarucizumab, a humanized monoclonal antibody fragment, for reversal of Dabigatran therapy for atrial fibrillation

Centurión¹,

Aquino²,

García³

et al. 2017

Blood Heart Circ

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The prevalence of atrial fibrillation (AF) increases with age, and the elderly are the fastest growing subset of the population. It has been estimated that there will be 12 million patients with AF in the United States within the next several decades [1][2][3][4][5]. Actually, AF is the most common sustained arrhythmia encountered in the field of internal medicine. AF has a prevalence of approximately 1% and a lifetime risk of approximately 25% after the age of 40 [1,2]. The annual risk of stroke ranges from 2%-18% depending on other risk factors [3]. Atrial fibrillation shares strong epidemiological associations with other cardiovascular diseases such as heart failure and coronary artery disease [6][7][8][9][10]. Many fundamental aspects of AF have been poorly understood until quite recently, and there are several features on the mechanisms of AF that makes it difficult to manage it properly [10][11][12]. AF may present in a wide variety of clinical conditions. The optimal management strategy for an individual patient with AF depends on the patient's underlying condition.AF increases the overall risk of stroke five-fold, and is associated with particularly severe strokes. About 76% of AF patients have a moderate to high risk of embolic complications, and they have also a significant risk factor for stroke recurrence [13][14][15]. Therefore, AF carries a high risk for thromboembolic events and any patient with at least two moderate risk factors, and probably even one, should be on oral anticoagulation. Balancing the risk of bleeding and thromboembolism is crucial in the management of patients with AF. Antithrombotic therapy reduces the risk of stroke in patients with AF, and Warfarin has been shown to have a relative risk reduction of approximately 60% compared with control and to be significantly more effective than Aspirin [16,17]. Therefore, for over five decades, oral anticoagulation with Warfarin has become the standard of care for stroke prevention in patients with AF [18]. Warfarin, however, has limitations, including multiple interactions with other drugs and foods, genetic variability in metabolism, delayed onset and offset, and the need for frequent monitoring and dose adjustments. Given the limitations of Warfarin, clinicians and clinical investigators have been interested in the development of newer oral anticoagulants [19][20][21]. Therefore, there have been studies investigating the efficacy and safety of these agents. The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) was a large, multicenter, randomized trial designed to compare two fixed doses of Dabigatran (110 mg and 150 mg), each administered in a blinded manner, with open-label use of Warfarin in AF patients who were at increased risk for stroke [19]. The primary study outcome was stroke or systemic embolism. The primary safety outcome was major hemorrhage. Secondary outcomes were stroke, systemic embolism, and death. Other outcomes were myocardial infarction, pulmonary embolism, transient ischemic attack, and hospitaliza...

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“…With half-lives of about 12 hours, the ODIs also have a rapid offset of action [17]. All-oral regimens of revaroxaban and apixaban are available out-of-hospital treatment [17].…”

Section: New Oral Anticoagulants: the Direct Oral Inhibitorsmentioning

confidence: 99%

Oral Direct Anticoagulants in Thrombosis Management in Anti-Phospholipid Syndrome: Unanswered Questions

G¹

2015

J Hematol Thrombo Dis

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Anti-phospholipid syndrome comprises a broad spectrum of manifestations with thrombotic events as a serious issue. The current mainstay of treatment for thrombotic anti-phospholipid syndrome is heparin followed by long-term anticoagulation with vitamin K antagonists. Vitamin K antagonists' management in this group of patients is frequently cumbersome, requires close monitoring and may affect patient's quality of life. There is also a high recurrence rate in high risk patients. The introduction of the oral direct inhibitors of coagulation for the management for thromboembolism is currently established for several indications.These agents are fixed dose with predictable anticoagulant effect and do not interact with dietary constituents and have few drug interactions. They have a rapid onset of action and don't routinely require monitoring. The shortcomings of vitamin K antagonists and the advantages of the oral direct inhibitors encouraged their trial in antiphospholipid syndrome. Case series of their use paved the road for designing clinical trials aiming to study their potential role in this important group of patients.In this article, we reviewed the literature regarding the current state of oral direct anticoagulants in thrombosis management in general, cited the case series results and presented the ongoing clinical trials that are currently underway. We also raise some practical points relevant to their application in specific situations. It is premature to pass comments on their applicability, but the seriousness of the issue

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Evolving use of new oral anticoagulants for treatment of venous thromboembolism

Cited by 120 publications

References 45 publications

Apixaban for the Treatment of Japanese Subjects With Acute Venous Thromboembolism (AMPLIFY-J Study)

Apixaban for the Treatment of Japanese Subjects With Acute Venous Thromboembolism (AMPLIFY-J Study)

Idarucizumab, a humanized monoclonal antibody fragment, for reversal of Dabigatran therapy for atrial fibrillation

Oral Direct Anticoagulants in Thrombosis Management in Anti-Phospholipid Syndrome: Unanswered Questions

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