Impact of weight on the efficacy and safety of direct-acting oral anticoagulants in patients with non-valvular atrial fibrillation: a meta-analysis

EP Europace ◽  
2020 ◽  
Vol 22 (3) ◽  
pp. 361-367 ◽  
Author(s):  
Aaqib H Malik ◽  
Srikanth Yandrapalli ◽  
Suchith Shetty ◽  
Wilbert S Aronow ◽  
Diwakar Jain ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Outcome Data ◽  
Phase Iii ◽  
Safety And Efficacy ◽  
Low Bmi ◽  
Direct Acting ◽  
The Impact ◽  
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.

scholarly journals Prescribing and Safety of Direct-Acting Oral Anticoagulants Compared to Warfarin in Patients with Atrial Fibrillation on Chronic Hemodialysis

Pharmacy ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 37 ◽  
Author(s):  
Estella Davis ◽  
Dallin Darais ◽  
Kevin Fuji ◽  
Paige Nekola ◽  
Khalid Bashir
Keyword(s):  
Atrial Fibrillation ◽  
Oral Anticoagulants ◽  
Chronic Hemodialysis ◽  
Average Dose ◽  
Chi Square ◽  
Direct Acting ◽  
Risk For Bleeding ◽  
The Impact ◽  
Area Health ◽  
Direct Acting Oral Anticoagulants

ESRD patients receiving hemodialysis (HD) were excluded from landmark trials evaluating direct-acting oral anticoagulants (DOACs) in atrial fibrillation (AF). The objective was to evaluate prescribing and bleeding with DOACs compared to warfarin in AF patients with chronic HD. A retrospective, observational study of patients receiving warfarin or DOAC from April 2010-April 2016 from area health system hospitals and Dialysis Clinics, Inc. records. Data was analyzed using descriptive statistics, ANOVA, and chi-square. Ninety-one patients were included with warfarin as the initial OAC in most patients (n = 76) at average dose of 29 mg/week. Fifteen patients were initially prescribed apixaban (n = 12) or dabigatran (n = 3). Most switches in OAC therapy were to apixaban. When the initial OAC was a DOAC, it was not dosed appropriately in five with one bleed, two dosed appropriately had bleeds. When initial warfarin was switched to a DOAC, it was not dosed appropriately in seven with five bleeds. More bleeds occurred with warfarin alone (n = 18) vs. those on warfarin switched to DOAC (n = 5) vs. DOAC alone (n = 3), p = 0.022. All but four patients that bled had HAS-BLED scores three or higher. Warfarin was most often prescribed and associated with a higher incidence of bleeding compared to DOACs in this population of patients at high risk for bleeding. Larger studies should be conducted to analyze the impact of DOAC dose appropriateness on safety and clinical outcomes.

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

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

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

Stroke ◽  
2020 ◽  
Vol 51 (8) ◽  
pp. 2364-2373 ◽  
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.

Abstract 160: Impact of Medication Adherence on Risk of Stroke, Major Bleeding and Other Outcomes in Atrial Fibrillation Patients Using Novel Oral Anticoagulants (Dabigatran and Rivaroxaban)

2017 ◽  
Vol 10 (suppl_3) ◽  
Author(s):  
Chinmay G Deshpande ◽  
Cynthia Willey Temkin ◽  
Robert Laforge ◽  
Stephen Kogut
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Drug Use ◽  
Propensity Score ◽  
Major Bleeding ◽  
Cox Regression ◽  
Oral Anticoagulants ◽  
Cox Models ◽  
Adherence Assessment ◽  
The Impact

Introduction: Dabigatran and Rivaroxaban have shown better or similar efficacy to lower stroke risk compared to warfarin in clinical trials. Evidence suggests adherence to cardiac drugs tend to reduce outcomes and cost. Our study is the first to examine the impact of atleast 6 to 12 month adherence to NOACs on ischemic stroke, major bleeding, Deep Vein Thrombosis and Pulmonary Embolism (DVTPE) risk in a propensity score based matched sample. Methods: A retrospective cohort study utilized de-identified data from Optum® Clinformatics™ Data Mart database (OptumInsight, Eden Prairie, MN) (Jan 1, 2010 and Dec 31, 2012). Adult patients with ≥ 1 diagnosis of atrial fibrillation or flutter (ICD9 427.31/32), >1 prescription of NOACs, 6 months pre-index continuous enrollment and CHA2DS2VASC score >1 were included. Adherence was calculated using Proportion of Days Covered (PDC ≥80%) for atleast 6 and 12 months of NOAC use and cohorts (adherent vs. non adherent) were matched on propensity score using Inverse Probability Treatment Weighting (IPTW) controlling for demographic and clinical characteristics at baseline. The risk of ischemic stroke, major bleeding (primary outcomes) and DVTPE (exploratory outcome) was evaluated for the matched cohorts post adherence assessment using Cox regression. Results: Out of 25,150 NOAC patients, a total of 3,629 and 1,946 patients with atleast 6 and 12 months of NOAC use were included. Across 2 cohorts, the mean age of the sample was 65 years, 65% were males and >60% had a moderate-high risk of stroke (CHA2DS2VASC>2). Adherence (PDC ≥80%) was 77% and 76% for patients with 6 and 12 month drug use. Post 12 months of drug use, the overall incidence of bleeding, stroke, and DVTPE in the follow-up period was 4.42%, 1.80%, and 0.82% respectively. Each outcome was analyzed separately to avoid calculation of competing risks. Using Cox models with IPTW balanced cohorts, non-adherence was significantly (p ≤0.05) associated with an increase in stroke (≥ 1.5 fold) and DVTPE (≥ 2 fold) risk in both 6 and 12 month users. The risk of bleeding was not significantly different across adherent vs. non adherent users (Table). Conclusion: In our sample, adherence to NOACs was associated with a reduction in stroke and DVTPE risk but did not substantially increase bleeding risk. Further studies with newer NOACs are warranted.

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

2021 ◽  
Author(s):  
Phannita Wattanaruengchai ◽  
Surakit Nathisuwan ◽  
Khemajira Karaketklang ◽  
Wanwarang Wongcharoen ◽  
Arintaya Phrommintikul ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Direct Acting ◽  
Direct Acting Oral Anticoagulants

scholarly journals Efficacy and Safety of Direct Oral Anticoagulants for Atrial Fibrillation Across Body Mass Index Categories

2020 ◽  
Vol 9 (24) ◽  
Author(s):  
Rachel M. Kaplan ◽  
Yoshihiro Tanaka ◽  
Rod S. Passman ◽  
Michelle Fine ◽  
Laura J. Rasmussen‐Torvik ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Body Mass Index ◽  
Body Mass ◽  
Intracranial Hemorrhage ◽  
Oral Anticoagulants ◽  
Efficacy And Safety ◽  
Class 1 ◽  
Direct Acting ◽  
Direct Acting Oral Anticoagulants

Background Direct‐acting oral anticoagulants are now the preferred method of anticoagulation in patients with atrial fibrillation. Limited data on efficacy and safety of these fixed‐dose regimens are available in severe obesity where drug pharmacokinetics and pharmacodynamics may be altered. The objectives of this study were to evaluate efficacy and safety in patients with atrial fibrillation taking direct‐acting oral anticoagulants across body mass index (BMI) categories in a contemporary, real‐world population. Methods and Results We performed a retrospective study of patients with atrial fibrillation at an integrated multisite healthcare system. Patients receiving a direct‐acting oral anticoagulant prescription and ≥12 months of follow‐up between 2010 and 2017 were included. The primary efficacy and safety outcomes were ischemic stroke or systemic embolism and intracranial hemorrhage. We performed Cox proportional hazards modeling to compute hazard ratios (HRs) adjusted for CHA 2 DS 2 ‐VASc score to examine differences by excess BMI categories relative to normal BMI. Of 7642 patients, mean±SD age was 69±12 years with a median (interquartile range) follow‐up of 3.8 (2.2–6.0) years. Approximately 22% had class 1 obesity and 19% had class 2 or 3 obesity. Stroke risks were similar in patients with and without obesity (HR, 1.2; 95% CI, 0.5–2.9; and HR, 0.68; 95% CI, 0.23–2.0 for class 1 and class 2 or 3 obesity compared with normal BMI, respectively). Risk of intracranial hemorrhage was also similar in class 1 and class 2 or 3 obesity compared with normal BMI (HR, 0.64; 95% CI, 0.35–1.2; and HR, 0.66; 95% CI, 0.35–1.2, respectively). Conclusions Direct‐acting oral anticoagulants demonstrated similar efficacy and safety across all BMI categories, even at high weight values.

Do the Safety and Efficacy Outcomes Reported in the Clinical Trials of Direct Oral Anticoagulants (DOAC) Translate to the Real-World?

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2335-2335
Author(s):  
Shammim Haji ◽  
Jignesh P Patel ◽  
Vivian Auyeung ◽  
Lara N Roberts ◽  
Julia Czuprynska ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Major Bleeding ◽  
Real World ◽  
Research Funding ◽  
Oral Anticoagulants ◽  
Phase Iii ◽  
World Population ◽  
Safety And Efficacy ◽  
The Real ◽  
Pooled Data

Abstract Do the safety and efficacy outcomes reported in the clinical trials of direct oral anticoagulants (DOAC) translate to the 'real-world'? Background: A number of DOACs are now available for clinicians to prescribe in clinical practice. Whilst the results from large clinical trials demonstrate that these agents are as effective as vitamin K antagonists, there is some concern that the patients studied in the trials were not representative of patients, clinicians encounter in everyday practice. The aim of our study was to compare the real-world clinic population commenced on a DOAC to that from the clinical trials for these agents, in order to assess potential differences in safety and efficacy. Patients and methods: A retrospective observational cohort study was undertaken. Patients who were initiated on a DOAC (apixaban, dabigatran and rivaroxaban) at a large teaching hospital in South East London between 1st August 2012 and 31st July 2014 were identified through pharmacy issue data with those followed-up for a minimum of 6 months included. Baseline demographic data, rates of stroke/VTE and rates of major/non-major clinically relevant (NMCR) (ISTH definition) bleeding were assessed and compared to pooled data reported from the corresponding Phase III trials. Differences between groups were compared using t-tests or chi-squared tests. Results: During the review period, 748 patients were initiated on a DOAC, 365 for atrial fibrillation (AF) and 383 for venous thromboembolism (VTE). In terms of demographic differences, the real-world AF population comprised more females, were significantly older, had poorer renal function and a lower body weight. In contrast, the real-world VTE population typically had a higher body weight and poorer renal function, compared to the trial population, (table 1). Efficacy of DOACs was found to be similar across both the VTE and AF populations. With respect to safety, the real-world AF population experienced similar rates of major bleeding and a significantly lower rate of NMCR bleeding compared to the trial populations. In contrast, the real-world VTE population experienced a significantly higher rate of major bleeding, particularly gastrointestinal bleeding. Although the rate of NMCR bleeding was similar, there was a significantly higher rate of urogenital bleeding in the real-world VTE population, specifically heavy menstrual bleeding in women. Conclusions: The efficacy outcomes of DOAC use in a real-world AF and VTE population are consistent with the Phase III trials, despite some significant differences in baseline characteristics. However, a significantly increased rate of major bleeding was observed in the real-world VTE population, which requires further investigation. Table 1. Baseline demographic characteristics, efficacy and safety outcomes in the real-world population versus the trial population Atrial Fibrillation Venous Thromboembolism Trial population+N=28,342 Real-world population Trial population++ Real-world population N=365 N=8,716 N=383 Baseline Demographics, mean (SD) unless otherwise specified Age, years 72 (9.6) 76.8 * (12.1) 56.9 (14.2) 55.6 (18.7) Female (%) 10451 (36.9) 215 * (58.9) 3753 (43.1) 184 (48.0) Weight, kg 82.7 (19.5) 77.3 * (22.6) 84.9 (19.6) 88.2 * (23.0) Creatinine clearance, mL/min 69 (26.7) 58.1 * (26.9) 105.8 (40.7) 91.1 * (37.6) Concomitant aspirin therapy 10341 (36.5) 49 * (13.4) - 0 (0) Previous VKA use (%) 15711 (55.4) 193 (52.9) - 85 (22.2) Efficacy (%) All-cause mortality 1695 (6.0) 37 * (9.1) 160 (1.8) 10 (2.5) Stroke 676 (2.4) 8 (2.0) - 1 (0.3) VTE 39 (0.1) 1 (0.2) 192 (2.2) 7 (1.8) Safety (%) Major Bleeding 1419 (5.0) 17 (4.2) 79 (0.9) 15 * (3.8) Intracranial 170 (0.6) 1 (0.2) 6 (0.1) 2 * (0.5) Gastrointestinal 644 (2.3) 8 (2.0) 8 (0.1) 8 * (2.0) Non-major Clinically relevant (NMCR) bleeding 4824 (17.0) 30 * (7.4) 540 (6.2) 26 (6.6) Gastrointestinal - 9 (2.2) 53 (4.2) 10 (2.5) Urogenital 296 (4.2) 16 (3.9) 100 (2.5) 38 * (9.6) +Pooled data from ARISTOTLE, RE-LY and ROCKET-AF trials ++Pooled data from AMPLIFY, RE-COVER and EINSTEIN-PE/DVT trials *p<0.05 Disclosures Patel: Bayer plc: Research Funding. Auyeung:Bayer PLC: Research Funding. Arya:Bayer plc: Research Funding.

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