Systematic review and meta-analysis of the efficacy and safety of apixaban compared to rivaroxaban in acute VTE in the real world

Aryal, Madan Raj; Gosain, Rohit; Donato, Anthony A.; Yu, Han; Katel, Anjan; Bhandari, Yashoda; Dhital, Rashmi; Kouides, Peter A.

doi:10.1182/bloodadvances.2019000572

Cited by 38 publications

(38 citation statements)

References 19 publications

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“…After conducting network meta-analyses, for the first time, we found that apixaban ranked the best in both efficacy and safety for elderly patients with AF, especially in safety. Some realworld setting studies, systematic reviews, head-to-head clinical trials, and meta-analyses had recommended apixaban as the most effective and safe drug for anticoagulation, which was similar to our findings (19,(43)(44)(45)(46). Warfarin is known to increase vascular calcification, suggesting increased cardiovascular disease events.…”

Section: Discussionsupporting

confidence: 91%

Efficacy and Safety of Direct Oral Anticoagulants in Elderly Patients With Atrial Fibrillation: A Network Meta-Analysis

et al. 2020

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Background: Direct oral anticoagulants (DOACs) have been widely used in patients with atrial fibrillation (AF) for antithrombotic prophylaxis, which were shown to have a favorable risk-benefit profile. However, there are no guidelines for the use of DOACs in elderly patients (aged ≥75 years) with AF, which creates uncertainty about the optimal antithrombotic treatment in these patients. Methods: After comprehensively searching Embase, PubMed, and Cochrane databases, five phase III randomized controlled trials involving 28,137 elderly participants were included in this study. The efficacy outcome was stroke or systemic embolism, and the safety outcome was major bleeding. We conducted a network meta-analysis by using a Bayesian random-effect model for the first time to evaluate the efficacy and safety of main DOACs (apixaban, edoxaban, rivaroxaban, and dabigatran) and warfarin in elderly patients with AF. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were used to assess the effect of drugs on efficacy and safety. The rank probabilities were used to reflect the hierarchy of drugs, and a larger rank probability value symbolized a better rank of drugs. Results: In the prophylaxis of stroke or systemic embolism, apixaban was found to be the best among DOACs compared to warfarin (HR, 0.71; 95% CI: 0.33-1.50), though this finding was not statistically significant. Apixaban ranked the best (rank probabilities, 41.2%) in efficacy of drugs, followed by rivaroxaban, edoxaban, dabigatran, and warfarin (rank probabilities, 31.8, 15.9, 10.9, and 0.2%, respectively). In reducing the risk of major bleeding, apixaban was found to be the best among DOACs too, compared to warfarin (HR, 0.64; 95% CI: 0.33-1.30), though this finding was not statistically significant. In safety, apixaban ranked the best (rank probabilities, 71.4%), followed by edoxaban, dabigatran, warfarin, and rivaroxaban (rank probabilities, 21.0, 5.8, 0.9, and 0.8%, respectively). Conclusions: DOACs showed a lower incidence of stroke/systemic embolism and major bleeding compared with warfarin in antithrombotic therapy in elderly patients (aged ≥75 years), with apixaban being the best of those interventions. Therefore, apixaban should be given priority as an anticoagulant in stroke prevention for elderly patients with AF.

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Section: Discussionsupporting

confidence: 91%

Efficacy and Safety of Direct Oral Anticoagulants in Elderly Patients With Atrial Fibrillation: A Network Meta-Analysis

et al. 2020

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“…A systematic review including five large observational cohorts showed a 0.6 to 3.6% 3 months major bleeding rate in patients treated with apixaban for acute VTE. 26 Same proportions of major bleeding associated with DOAC therapy (3.3% during a mean follow-up of 85 days) were observed in a large practice-based multicenter, population study, although most DOAC users in this study used rivaroxaban. 27 The main limitation is the presence of selection bias as we do not know in how many patients (and why) another anticoagulant strategy than apixaban was chosen.…”

Section: Discussionsupporting

confidence: 48%

Effectiveness and Safety of Apixaban for Treatment of Venous Thromboembolism in Daily Practice

Hendriks

Klok

Stenger

et al. 2020

TH Open

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Introduction Phase 3 trials have shown comparable efficacy of direct oral anticoagulants (DOACs) and vitamin K antagonists in patients with acute venous thromboembolism (VTE), with less major bleeding events in patients randomized to DOAC treatment. With DOACs being increasingly used in clinical practice, evaluation of the DOACs in daily practice-based conditions is needed to confirm their safety and effectiveness. The aim of this study is to evaluate the effectiveness and safety of apixaban in VTE patients in daily practice. Methods In this retrospective cohort study, consecutive patients diagnosed with VTE in two Dutch hospitals (Leiden University Medical Center, Leiden and Haga Teaching Hospital, The Hague) were identified based on administrative codes. We assessed recurrent VTE, major bleeding and mortality during a 3-month follow-up period in those treated with apixaban. Results Of 671 consecutive VTE patients treated with apixaban, 371 presented with acute pulmonary embolism (PE) and 300 patients with deep-vein thrombosis. During 3 months treatment, 2 patients had a recurrent VTE (0.3%; 95% confidence interval [CI]: 0.08–1.1), 12 patients had major bleeding (1.8%; 95% CI: 1.0–3.2), and 11 patients died (1.6%; 95% CI: 0.9–2.9), of which one patient with recurrent PE and one because of a intracerebral bleeding. Conclusion In this daily practice-based cohort, apixaban yielded a low incidence of recurrent VTE, comparable to the phase 3 AMPLIFY study patients. The incidence of major bleeding was higher than in the AMPLIFY-study patients, reflecting the importance of daily practice evaluation and the fact that results from phase III clinical studies cannot be directly extrapolated toward daily practice.

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“…25) MARINER is another trial that was conducted in medically ill patients which showed that rivaroxaban 10 mg daily, given to medical patients for 45 days after hospital discharge, was not associated with a significantly lower risk of symptomatic VTE and related death compared to placebo. 29) Though there are now several options for extended duration VTE prophylaxis in acutely ill medical patients, the utilization of this practice within our current medical system remains limited. Additionally, this practice has not yet been adopted into current standard VTE prophylaxis Skeik N and Westergard E recommendations.…”

Section: Extended Prophylaxis After Dischargementioning

confidence: 99%

Recommendations for VTE Prophylaxis in Medically Ill Patients

Skeik

Westergard

2020

Annals of Vascular Diseases

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Venous thromboembolism (VTE) remains highly prevalent in medically ill patients, and often leads to increased mortality and cost burden during hospitalization and post-discharge. Nearly half of all VTEs occur during or after hospitalization, with pulmonary embolism accounting for 10% of inpatient mortality. Appropriate prophylaxis in high-risk medically ill patients has been shown to reduce risk of VTE and related mortality. Despite current evidence-based guidelines, VTE prophylaxis has been under-used. This owes greatly to ambiguity and concerns related to appropriate patient and prophylactic agent selection, and duration of prophylaxis. Because many acutely ill medical patients have multiple comorbidities, the risk of major bleeding must be considered when choosing to implement pharmacological VTE prophylaxis. Multiple risk assessment models have been developed and validated to help estimate VTE and bleeding risks in this population. While studies have shown that the risk for VTE often extends far beyond hospital discharge, there is no evidence to support extending prophylaxis after hospital discharge. The appropriate selection of VTE prophylaxis requires consideration for cost, availability, patient preference, compliance, and underlying comorbidities. Our paper reviews the current evidence and reasoning for appropriate selection of VTE prophylaxis in acutely medical ill patients, and highlights our own approach and recommendations.

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Systematic review and meta-analysis of the efficacy and safety of apixaban compared to rivaroxaban in acute VTE in the real world

Cited by 38 publications

References 19 publications

Efficacy and Safety of Direct Oral Anticoagulants in Elderly Patients With Atrial Fibrillation: A Network Meta-Analysis

Efficacy and Safety of Direct Oral Anticoagulants in Elderly Patients With Atrial Fibrillation: A Network Meta-Analysis

Effectiveness and Safety of Apixaban for Treatment of Venous Thromboembolism in Daily Practice

Recommendations for VTE Prophylaxis in Medically Ill Patients

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