Comparison of the HAS‐BLED versus ORBIT Scores in Predicting Major Bleeding Among Asians Receiving the Direct‐Acting Oral Anticoagulants

Abstract Aims This study sought to determine the impact of weight and body mass index (BMI) on the safety and efficacy of direct-acting oral anticoagulants (DOACs) compared with warfarin in patients with non-valvular atrial fibrillation. Methods and results A systematic literature search was employed in PubMed, Embase, and Cochrane clinical trials with no language or date restrictions. Randomized trials or their substudies were assessed for relevant outcome data for efficacy that included stroke or systemic embolization (SSE), and safety including major bleeding and all-cause mortality. Binary outcome data and odds ratios from the relevant articles were used to calculate the pooled relative risk. For SSE, the data from the four Phase III trials showed that DOACs are better or similarly effective with low BMI 0.73 (0.56–0.97), normal BMI 0.72 (0.58–0.91), overweight 0.87 (0.76–0.99), and obese 0.87 (0.76–1.00). The risk of major bleeding was also better or similar with DOACs in all BMI subgroups with low BMI 0.62 (0.37–1.05), normal BMI 0.72 (0.58–0.90), overweight 0.83 (0.71–0.96), and obese 0.91 (0.81–1.03). There was no impact on mortality in all the subgroups. In a meta-regression analysis, the effect size advantage of DOACs compared with warfarin in terms of safety and efficacy gradually attenuated with increasing weight. Conclusion Our findings suggest that a weight-based dosage adjustment may be necessary to achieve optimal benefits of DOACs for thromboembolic prevention in these patients with non-valvular atrial fibrillation. Further dedicated trials are needed to confirm these findings. PROSPERO 2019 CRD42019140693. Available from: https://www.crd.york.ac.uk/prospero/display_record.php? ID=CRD42019140693.

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Meta-analysis comparing the efficacy and safety of direct acting oral anticoagulants to warfarin in patients with atrial fibrillation with and without diabetes

European Heart Journal ◽

10.1093/ehjci/ehaa946.3378 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

S Shetty ◽

H Malik

Keyword(s):

Atrial Fibrillation ◽

Major Bleeding ◽

Meta Analysis ◽

Oral Anticoagulants ◽

P Value ◽

Efficacy And Safety ◽

Systemic Embolization ◽

Direct Acting ◽

Direct Acting Oral Anticoagulants

Abstract Background Direct-acting oral anticoagulants (DOACs) are now the preferred choice over warfarin in patients with atrial fibrillation (AF). The comparative efficacy and safety of DOACs over warfarin in patients with and without diabetes mellitus (DM) has not been fully evaluated. Purpose To evaluate the efficacy and safety of DOACs compared to warfarin in patients with non-valvular atrial fibrillation with and without DM. Methods A comprehensive review of the literature was performed to identify RCTs with data on DOACs compared to warfarin in the subgroups of DM and nonN-DM. Our outcome of interest were stroke/systemic embolization (SSE) and major bleeding. A random-effects meta-analysis was performed. We further performed a network meta-analysis to assess the most effective of all the therapies for the above mentioned subgroups. Results Our search identified 4 RCTs with 71,683 randomized patients, of which 22,087 were DM and 49,596 were non-DM. The mean duration of follow up was 2.3 years. Our results showed that the DOACS were associated with lower odds for SSE in diabetics (OR 0.80; 95% CI 0.67–0.95; p-value=0.01) and non-diabetics (OR 0.81; 95% CI 0.71–0.92; p-value<0.01). For major bleeding, DOACs were non-inferior to warfarin in DM (OR 0.94; 95% CI 0.80–1.09; p-value=0.42) and non-DM (OR 0.82; 95% CI 0.62–1.07; p-value=0.15). (Fig 1) Network meta-analysis showed that dabigatran was the most effective for the outcome of SSE irrespective of DM status. However, edoxaban and apixaban were the safest of the DOACs for the outcome of major bleeding (Table 1) Conclusion In this meta-analysis of RCT, we found that DOACs are more effective and similarly safe compared to warfarin irrespective of the diabetic status of the patient. Funding Acknowledgement Type of funding source: None

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Direct-Acting Oral Anticoagulants Versus Warfarin in Medicare Patients With Chronic Kidney Disease and Atrial Fibrillation

Stroke ◽

10.1161/strokeaha.120.028934 ◽

2020 ◽

Vol 51 (8) ◽

pp. 2364-2373 ◽

Cited By ~ 7

Author(s):

James B. Wetmore ◽

Nicholas S. Roetker ◽

Heng Yan ◽

Jorge L. Reyes ◽

Charles A. Herzog

Keyword(s):

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Major Bleeding ◽

Oral Anticoagulants ◽

Systemic Embolism ◽

Intention To Treat ◽

Hazard Ratios ◽

Direct Acting ◽

Direct Acting Oral Anticoagulants

Background and Purpose: The comparative effectiveness of direct-acting oral anticoagulants, compared with warfarin, for risks of stroke/systemic embolism, major bleeding, or death have not been studied in Medicare beneficiaries with atrial fibrillation and nondialysis-dependent chronic kidney disease. Methods: Medicare data from 2011 to 2017 were used to identify patients with stages 3, 4, or 5 chronic kidney disease and new atrial fibrillation who received a new prescription for warfarin, apixaban, rivaroxaban, or dabigatran. We estimated marginal hazard ratios with 95% CIs for the association of each direct-acting oral anticoagulant, compared with warfarin, for the outcomes of interest using inverse-probability-of-treatment weighted Cox proportional hazards models in as-treated and intention-to-treat analyses. Results: A total of 22 739 individuals met criteria (46.3% warfarin, 29.6% apixaban, 17.2% rivaroxaban, 6.9% dabigatran). Across the groups of anticoagulant users, mean age was 78.4 to 79.0 years; 50.3% to 51.4% were women, and 80.3% to 82.8% had stage 3 chronic kidney disease. In the as-treated analysis, for stroke/systemic embolism, hazard ratios, all compared with warfarin, were 0.70 (0.51–0.96) for apixaban, 0.80 (0.54–1.17) for rivaroxaban, and 1.15 (0.69–1.94) for dabigatran. For major bleeding, analogous hazard ratios were 0.47 (0.37–0.59) for apixaban, 1.05 (0.85–1.30) for rivaroxaban, and 0.95 (0.70–1.31) for dabigatran. There was no difference in the risk of all-cause mortality between the direct-acting oral anticoagulants and warfarin. Results of the intention-to-treat analysis were similar. Conclusions: Apixaban, compared with warfarin, was associated with decreased risk of stroke/systemic embolism and major bleeding; risks for both outcomes with rivaroxaban and dabigatran did not differ from risks with warfarin.

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Anticoagulation for the Treatment of Cancer-Associated Thrombosis: A Systematic Review and Network Meta-Analysis of Randomized Trials

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029618800792 ◽

2018 ◽

Vol 24 (9_suppl) ◽

pp. 182S-187S ◽

Cited By ~ 15

Author(s):

Diana M. Sobieraj ◽

William L. Baker ◽

Eni Smith ◽

Katarzyna Sasiela ◽

Stephanie E. Trexler ◽

...

Keyword(s):

Major Bleeding ◽

Meta Analysis ◽

Oral Anticoagulants ◽

Low Molecular Weight ◽

Low Molecular Weight Heparins ◽

All Cause Mortality ◽

Recurrent Vte ◽

Direct Acting ◽

Cancer Associated Thrombosis ◽

Direct Acting Oral Anticoagulants

To perform a systematic review and network meta-analysis evaluating the efficacy and safety of low-molecular-weight heparins (LMWHs), vitamin K antagonists (VKAs), and direct-acting oral anticoagulants (DOACs) for the treatment of cancer-associated thrombosis (CAT). We searched MEDLINE, Cochrane Central Register of Controlled Trials, and conference abstracts through March 2018. Randomized controlled trials (RCTs) enrolling adults with CAT comparing 2 or more full-dose anticoagulants (LMWH, VKA, and DOAC) and evaluating recurrent venous thromboembolism (VTE), major bleeding, and/or all-cause mortality were included. Reviewers identified studies, extracted data, and assessed the quality of the evidence in duplicate. A frequentist network meta-analysis, which uses direct and indirect evidence to simultaneously compare multiple interventions, was performed using a random-effects approach. Results are reported as pooled relative risks (RRs) with 95% confidence intervals (CIs). We included 13 RCTs (n = 6292): 7 compared LMWHs with VKAs, 4 compared DOACs with VKAs, and 2 compared DOACs with LMWHs. The risk of recurrent VTE was significantly reduced by 28% and 54% with a DOAC compared to an LMWH and a VKA, respectively. Low-molecular-weight heparins significantly reduced the risk of recurrent VTE by 36% versus VKAs. The risk of major bleeding was 14% higher with DOACs compared to LMWHs and 15% and 25% lower with DOACs and LMWHs versus VKAs, although 95% CIs included unity for each. The risk of all-cause mortality appeared similar for all 3 comparisons (RR = 1.0 for each comparison). Direct-acting oral anticoagulants appeared superior in reducing recurrent VTE in patients with CAT compared to LMWH and VKAs, but an increased risk of major bleeding versus LMWH cannot be ruled out.

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Reversal of DIRECT-ACTING Oral Anticoagulants in Urgent Surgery of the Proximal Aorta: case Series and Review of the literature

Current Pharmaceutical Design ◽

10.2174/1381612825666181226150006 ◽

2019 ◽

Vol 24 (38) ◽

pp. 4534-4539 ◽

Cited By ~ 1

Author(s):

Eric Zimmermann ◽

Fawzi Ameer ◽

Berhane Worku ◽

Dimitrios Avgerinos

Keyword(s):

Oral Anticoagulants ◽

Aortic Surgery ◽

Management Strategies ◽

Case Series ◽

Published Data ◽

Review Of Literature ◽

Clotting Factors ◽

Urgent Surgery ◽

Direct Acting ◽

Direct Acting Oral Anticoagulants

Introduction: Proximal aorta interventions impose significant bleeding risk. Patients on concomitant anticoagulation regimens compound the risk of bleeding in any surgery, but especially cardiothoracic interventions. The employment of direct-acting oral anticoagulants (DOAC), namely those that target clotting factors II or X, has expanded at a precipitous rate over the last decade. The emergence of their reversal agents has followed slowly, leaving clinicians with management dilemmas in urgent surgery. We discuss current reversal strategies based on the available published data and our experience with proximal aortic surgery in patients taking DOACs. Literature Search: We performed a review of literature and present three cases from our experience to offer insight into management strategies that have been historically successful. A review of literature was conducted via PubMed with the following search string: (NOAC or DOAC or TSOAC) and (aorta or aortic or (Stanford and type and a)). Case Presentation: We present three case presentations that illustrate the importance of DOAC identification and offer management strategies in mitigating associated bleeding risks in urgent or emergent surgeries. Conclusion: Treatment teams should be aware of the technical limitations of identifying and reversing DOACs. In view of the tendency toward publishing positive outcomes, more scientific rigor is required in the area of emergency DOAC reversal strategies.

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