Impact of age, comorbidity, and polypharmacy on the efficacy and safety of edoxaban for the treatment of venous thromboembolism: An analysis of the randomized, double-blind Hokusai-VTE trial

Vanassche, Thomas; Verhamme, Peter; Wells, Philip S.; Segers, Annelise; Ageno, Walter; Brekelmans, Marjolein P. A.; Chen, Cathy Z.; Cohen, Alexander T.; Grosso, Michael; Medina, Andria P.; Mercuri, Michele; Winters, Shannon M; Zhang, George; Weitz, Jeffrey I.; Raskob, Gary E.; Büller, Harry R.

doi:10.1016/j.thromres.2017.12.005

Cited by 29 publications

(19 citation statements)

References 20 publications

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“…The AMPLIFY trial noted improved efficacy and safety of apixaban (10 mg twice daily for 7 days followed by 5 mg twice daily for 6 months) compared to standard therapy (enoxaparin followed by warfarin) in patients ≥75 years [64], whereas the RE-COVER II trial, which compared dabigatran to warfarin, found that efficacy and risk of bleeding increased exponentially with age with dabigatran and decreased with warfarin [65]. The Hokusai-VTE study, comparing edoxaban to warfarin, observed an increased bleeding risk linked to age regardless of treatment, but noted a reduction in recurrent VTE for patients > 80 years of age on the DOAC regimen [66]. In the EINSTEIN-DVT and PE trials, there was a 1.4% reduction in recurrent VTE events and a 3.3% reduction in major bleeding in patients ≥75 years of age receiving rivaroxaban compared to standard enoxaparin/VKA treatment [67].…”

Section: Methodsmentioning

confidence: 99%

Evaluation of unmet clinical needs in prophylaxis and treatment of venous thromboembolism in at-risk patient groups: pregnancy, elderly and obese patients

et al. 2019

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BackgroundVenous thromboembolism (VTE) accounts for an estimated 900,000 cases per year in the US alone and constitutes a considerable burden on healthcare systems across the globe.ObjectiveTo understand why the burden is so high, qualitative and quantitative research was carried out to gain insights from experts, guidelines and published studies on the unmet clinical needs and therapeutic strategies in VTE prevention and treatment in three populations identified as being at increased risk of VTE and in whom VTE prevention and treatment were regarded as suboptimal: pregnant women, the elderly and obese patients.MethodologyA gap analysis methodology was created to highlight unmet needs in VTE management and to discover the patient populations considered most at risk. A questionnaire was devised to guide qualitative interviews with 44 thrombosis and haemostasis experts, and a review of the literature on VTE in the specific patient groups from 2015 to 2017 was completed. This was followed by a Think Tank meeting where the results from the research were discussed.ResultsThis review highlights the insights gained and examines in detail the unmet needs with regard to VTE risk-assessment tools, biomarkers, patient stratification methods, and anticoagulant and dosing regimens in pregnant women, the elderly and obese patients.ConclusionsSpecifically, in pregnant women at high risk of VTE, low-molecular-weight heparin (LMWH) is the therapy of choice, but it remains unclear how to use anticoagulants when VTE risk is intermediate. In elderly patients, evaluation of the benefit of VTE prophylaxis against the bleeding risk is particularly important, and a head-to-head comparison of efficacy and safety of LMWH versus direct oral anticoagulants is needed. Finally, in obese patients, lack of guidance on anticoagulant dose adjustment to body weight has emerged as a major obstacle in effective prophylaxis and treatment of VTE.

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Section: Methodsmentioning

confidence: 99%

Evaluation of unmet clinical needs in prophylaxis and treatment of venous thromboembolism in at-risk patient groups: pregnancy, elderly and obese patients

et al. 2019

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“…As far as safety profiles concerned, it has been shown a significant reduction in risk of major bleeding for older patients taking apixaban or rivaroxaban compared to warfarin 73,76 . In contrast, there was a non-significant difference in major bleeding for dabrigatran and edoxaban compared with warfarin in the older and in the total patient population 74,75 . In addition to these studies, very few real world studies have been conducted to compare the safety and effectiveness between DOACs focusing on very old patients.…”

Section: Thromboprophylaxis and Risk Of Bleeding In Older Populationmentioning

confidence: 78%

“…The RE-COVER II trial found that dabigatran 150 mg twice daily was non inferior to warfarin, in reducing the risk of recurrent VTE in the older population 74 . The Hokusai-VTE study, comparing edoxaban to warfarin, observed a significant reduction in risk of VTE compared with warfarin in the older patient population 75 . In the EINSTEIN-DVT and PE trials rivaroxaban (15 mg twice daily for three weeks, then 20 mg once daily) was non inferior to warfarin bridged with enoxaparin in the reduction of VTE in both elderly populations and in the total patient population 76 .…”

Section: Thromboprophylaxis and Risk Of Bleeding In Older Populationmentioning

confidence: 99%

Thromboembolic disease: a geriatric syndrome

Incalzi

2020

JGG

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“…23 The EINSTEIN DVT and EINSTEIN PE studies for rivaroxaban and Hokusai-VTE for edoxaban considered multimorbid patients in subgroup analyses. 65,66 In the pooled analysis of the EINSTEIN DVT and EINSTEIN PE, "fragile" patients were a group defined by the presence of !1 of the following criteria: age >75 years, CrCl <50 mL/min or low body weight 50 kg. As expected, rates of recurrent VTE and bleeding were higher in the "fragile" (n ¼ 1,573) versus "nonfragile" (n ¼ 6,709) populations.…”

Section: Recently Published Guidance Also Suggests Edoxaban and Rivarmentioning

confidence: 99%

Treatment of Venous Thromboembolism in Special Populations with Direct Oral Anticoagulants

2020

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As a result of the successful completion of their respective phase III studies compared with vitamin K antagonists (VKAs), four direct oral anticoagulants (DOACs) have been approved for the treatment and secondary prevention of venous thromboembolism (VTE). These DOACs—apixaban, dabigatran, edoxaban, and rivaroxaban—have subsequently seen a steady uptake among clinicians since their approval. Despite the suitability of DOACs for a broad range of patients, they are not appropriate in certain situations, whereas in others they require additional considerations such as dose reductions. Subanalyses of phase III trials and studies on specific VTE patient populations have been conducted to evaluate the safety and efficacy of the DOACs in a broad range of settings, such as patients with renal impairment, patients with cancer, patients of childbearing potential, patients with multiple comorbidities and pediatric patients. Furthermore, many recent guidance documents from important hematological societies and other specialists have incorporated several of these developments. These documents also identify the patients for whom DOACs are not suitable and where traditional anticoagulation options such as heparins or VKAs should be considered instead. This review provides an overview of key VTE patient subgroups, the clinical evidence supporting the use of anticoagulation in these patients, and a discussion of the most appropriate approaches to their management, including considerations such as dosing, acute and extended treatment durations, and DOAC selection.

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Impact of age, comorbidity, and polypharmacy on the efficacy and safety of edoxaban for the treatment of venous thromboembolism: An analysis of the randomized, double-blind Hokusai-VTE trial

Cited by 29 publications

References 20 publications

Evaluation of unmet clinical needs in prophylaxis and treatment of venous thromboembolism in at-risk patient groups: pregnancy, elderly and obese patients

Evaluation of unmet clinical needs in prophylaxis and treatment of venous thromboembolism in at-risk patient groups: pregnancy, elderly and obese patients

Thromboembolic disease: a geriatric syndrome

Treatment of Venous Thromboembolism in Special Populations with Direct Oral Anticoagulants

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