scholarly journals Response by Wetmore et al to Letter Regarding Article, “Direct-Acting Oral Anticoagulants Versus Warfarin in Medicare Patients With Chronic Kidney Disease and Atrial Fibrillation”

Stroke ◽  
2020 ◽  
Vol 51 (12) ◽  
Author(s):  
James B. Wetmore ◽  
Nicholas S. Roetker ◽  
Charles A. Herzog
Stroke ◽  
2020 ◽  
Vol 51 (8) ◽  
pp. 2364-2373 ◽  
Author(s):  
James B. Wetmore ◽  
Nicholas S. Roetker ◽  
Heng Yan ◽  
Jorge L. Reyes ◽  
Charles A. Herzog

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.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Hamatani ◽  
M Iguchi ◽  
Y Aono ◽  
K Ishigami ◽  
S Ikeda ◽  
...  

Abstract Background Atrial fibrillation (AF) increases the risk of death, stroke/systemic embolism and heart failure (HF). Plasma natriuretic peptide (NP) level is an important prognostic marker in HF patients. However, little is known regarding the prognostic significance of plasma NP level in AF patients without HF. Purpose The aim of this study is to investigate the relationship between plasma NP level and clinical outcomes such as all-cause death, stroke/systemic embolism and HF hospitalization during follow-up period in AF patients without HF. Methods The Fushimi AF Registry is a community-based prospective survey of AF patients in our city. The inclusion criterion of the registry is the documentation of AF at 12-lead electrocardiogram or Holter monitoring at any time, and there are no exclusion criteria. We started to enroll patients from March 2011, and follow-up data were available for 4,466 patients by the end of November 2019. From the registry, we excluded 1,220 patients without a pre-existing HF (defined as having one of the following; prior hospitalization for HF, New York Heart Association class ≥2, or left ventricular ejection fraction <40%). Among 3,246 AF patients without HF, we investigated 1,189 patients with the data of plasma BNP (n=401) or N-terminal pro-BNP (n=788) level at the enrollment. We divided the patients according to the quartile of each plasma BNP or NT-pro BNP level and compared the backgrounds and outcomes between these 4 groups stratified by plasma NP level. Results Of 1,189 patients, the mean age was 72.1±10.2 years, 454 (38%) were female and 684 (58%) were paroxysmal AF. The mean CHADS2 and CHA2DS2-VASc score were 1.6±1.1 and 2.9±1.5, respectively. Oral anticoagulants were prescribed in 671 (56%) at baseline. The median (interquartile range) BNP and N-terminal pro-BNP level were 84 (38, 176) and 500 (155, 984) pg/ml, respectively. Patients with high plasma NP level were older, and demonstrated lower prevalence of paroxysmal AF, higher CHADS2 and CHA2DS2-VASc scores and higher prevalence of chronic kidney disease and oral anticoagulants prescription (all P<0.01). A total of 165 all-cause death, 114 stroke/systemic embolism and 103 HF hospitalization occurred during the median follow-up period of 5.0 years. Kaplan-Meier curves demonstrated that higher plasma NP level was significantly associated with the incidences of all-cause death, stroke/systemic embolism and HF hospitalization in AF patients without HF (Figure 1A). Multivariable Cox regression analysis revealed that plasma NP level could stratify the risk of clinical outcomes even after adjustment by type of AF, CHA2DS2-VASc score, chronic kidney disease and oral anticoagulant prescription (Figure 1B). Conclusion Plasma NP level is a significant prognostic marker for all-cause death, stroke/systemic embolism and HF hospitalization in AF patients without HF, suggesting the importance of measuring plasma NP level in AF patients even without HF. Figure 1 Funding Acknowledgement Type of funding source: None


EP Europace ◽  
2020 ◽  
Vol 22 (3) ◽  
pp. 361-367 ◽  
Author(s):  
Aaqib H Malik ◽  
Srikanth Yandrapalli ◽  
Suchith Shetty ◽  
Wilbert S Aronow ◽  
Diwakar Jain ◽  
...  

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.


2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Emma Kirstine Laugesen ◽  
Laila Staerk ◽  
Nicholas Carlson ◽  
Anne-Lise Kamper ◽  
Jonas Bjerring Olesen ◽  
...  

Abstract Background We aimed to compare effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin-K antagonists (VKA) in atrial fibrillation (AF) patients with chronic kidney disease (CKD) not receiving dialysis. Methods By using personal identification numbers, we cross-linked individual-level data from Danish administrative registries. We identified every citizen with a prior diagnosis of AF and CKD who initiated NOAC or VKA (2011–2017). An external analysis of 727 AF patients with CKD (no dialysis) was performed to demonstrate level of kidney function in a comparable population. Study outcomes included incidents of stroke/thromboembolisms (TEs), major bleedings, myocardial infarctions (MIs), and all-cause mortality. We used Cox proportional hazards models to determine associations between oral anticoagulant treatment and outcomes. Results Of 1560 patients included, 1008 (64.6%) initiated VKA and 552 (35.4%) initiated NOAC. In a comparable population we found that 95.3% of the patients had an estimated glomerular filtration rate (eGFR) < 59 mL/min. Patients treated with NOAC had a significantly decreased risk of major bleeding (hazard ratio (HR): 0.47, 95% confidence interval (CI): 0.26–0.84) compared to VKA. There was not found a significant association between type of anticoagulant and risk of stroke/TE (HR: 0.83, 95% CI: 0.39–1.78), MI (HR: 0.45, 95% CI: 0.18–1.11), or all-cause mortality (HR: 0.99, 95% CI: 0.77–1.26). Conclusion NOAC was associated with a lower risk of major bleeding in patients with AF and CKD compared to VKA. No difference was found in risk of stroke/TE, MI, and all-cause mortality.


2020 ◽  
Vol 9 (24) ◽  
Author(s):  
Rachel M. Kaplan ◽  
Yoshihiro Tanaka ◽  
Rod S. Passman ◽  
Michelle Fine ◽  
Laura J. Rasmussen‐Torvik ◽  
...  

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.


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