Relationship between Chronic Kidney Disease, Time-in-Therapeutic Range, and Adverse Outcomes in Atrial Fibrillation: A post hoc Analysis from the AMADEUS Trial

2021 ◽  
pp. 1-7
Author(s):  
Wern Yew Ding ◽  
Gregory Y.H. Lip ◽  
Alena Shantsila

<b><i>Background:</i></b> The benefit of anticoagulation therapy in atrial fibrillation (AF) and chronic kidney disease (CKD) remains controversial. We aimed to evaluate the impact of renal function on the quality of anticoagulation control, and the effects of both these factors on outcomes in AF. <b><i>Methods:</i></b> Post hoc analysis of the AMADEUS trial. Trial-related outcomes were adjudicated and we studied the composite of first stroke/major bleeding/all-cause mortality, ischaemic stroke, major bleeding, all-cause mortality, and cardiovascular mortality. <b><i>Results:</i></b> We included 2,282 vitamin K antagonist (VKA)-treated patients {<i>n</i> = 787 (34.5%) females; median age 72 (interquartile ranges [IQR] 64–77) years}. Median follow-up was 365 (IQR 189–460) days. There were 1,922 (84.2%) non-CKD and 360 (15.8%) CKD patients. Renal function was inversely correlated with time-in-therapeutic range (<i>r</i> = −0.047, <i>p</i> = 0.025). There was no statistical difference in terms of crude study outcomes based on renal function. Multivariable regression analysis demonstrated that moderate renal failure with estimated glomerular filtration rate of less than 60 mL/min/1.73 m<sup>2</sup> (<i>p</i> = 0.032) and percentage of time-in-therapeutic range (<i>p</i> = 0.011) were independent predictors for the composite outcome of stroke, major bleeding, and all-cause mortality. <b><i>Conclusion:</i></b> Deteriorated renal function has a small negative impact on the quality of anticoagulation control with VKA which is linked to poor outcomes in AF. However, moderate renal failure itself was an independent risk factor for increased risk of stroke, major bleeding, and all-cause mortality amongst patients with AF.

2020 ◽  
Vol 103 (6) ◽  
pp. 548-552

Objective: To predict the quality of anticoagulation control in patients with atrial fibrillation (AF) receiving warfarin in Thailand. Materials and Methods: The present study retrospectively recruited Thai AF patients receiving warfarin for three months or longer between June 2012 and December 2017 in Central Chest Institute of Thailand. The patients were classified into those with SAMe-TT₂R₂ of 2 or less, and 3 or more. The Chi-square test or Fisher’s exact test was used to compare the proportion of the patients with poor time in therapeutic range (TTR) between the two groups of SAMe-TT₂R₂ score. The discrimination performance of SAMe-TT₂R₂ score was demonstrated with c-statistics. Results: Ninety AF patients were enrolled. An average age was 69.89±10.04 years. Most patients were persistent AF. An average CHA₂DS₂-VASc, SAMe-TT₂R₂, and HAS-BLED score were 3.68±1.51, 3.26±0.88, and 1.98±0.85, respectively. The present study showed the increased proportion of AF patients with poor TTR with higher SAMe-TT₂R₂ score. The AF patients with SAMe-TT₂R₂ score of 3 or more had a larger proportion of patients with poor TTR than those with SAMe-TT₂R₂ score of 2 or less with statistical significance when TTR was below 70% (p=0.03) and 65% (p=0.04), respectively. The discrimination performance of SAMe-TT₂R₂ score was demonstrated with c-statistics of 0.60, 0.59, and 0.55 when TTR was below 70%, 65% and 60%, respectively. Conclusion: Thai AF patients receiving warfarin had a larger proportion of patients with poor TTR when the SAMe-TT₂R₂ score was higher. The score of 3 or more could predict poor quality of anticoagulation control in those patients. Keywords: Time in therapeutic range, Poor quality of anticoagulation control, Warfarin, SAMe-TT₂R₂, Labile INR


2020 ◽  
Vol 9 (6) ◽  
pp. 1698 ◽  
Author(s):  
Rungroj Krittayaphong ◽  
Thoranis Chantrarat ◽  
Roj Rojjarekampai ◽  
Pongpun Jittham ◽  
Poom Sairat ◽  
...  

Background: Warfarin remains the most commonly used oral anticoagulant (OAC) in Thailand for stroke prevention among patients with non-valvular atrial fibrillation (NVAF). The aim of this study was to investigate the relationship between time in therapeutic range (TTR) after warfarin initiation and clinical outcomes of NVAF. Methods: TTR was calculated by the Rosendaal method from international normalized ratio (INR) data acquired from a nationwide NVAF registry in Thailand. Patients were followed-up every six months. The association between TTR and clinical outcomes was analyzed. Results: There was a total of 2233 patients from 27 hospitals. The average age was 68.4 ± 10.6 years. The average TTR was 53.56 ± 26.37%. Rates of ischemic stroke/TIA, major bleeding, ICH, and death were 1.33, 2.48, 0.76, and 3.3 per 100 person-years, respectively. When patients with a TTR < 65% were compared with those with TTR ≥ 65%, the adjusted hazard ratios (aHR) for the increased risks of ischemic stroke/TIA, major bleeding, ICH, and death were 3.07, 1.90, 2.34, and 2.11, respectively. Conclusion: Poor TTR control is associated with adverse clinical outcomes in patients with NVAF who were on warfarin. Efforts to ensure good TTR (≥65%) after initiation of warfarin are mandatory to minimize the risk of adverse clinical outcomes.


2021 ◽  
Vol 8 ◽  
Author(s):  
Nur Azyyati Zawawi ◽  
Izzati Abdul Halim Zaki ◽  
Long Chiau Ming ◽  
Hui Poh Goh ◽  
Hanis Hanum Zulkifly

Vitamin K antagonist such as warfarin reduces the risk of stroke in atrial fibrillation (AF) patients. Since warfarin has a narrow therapeutic index, its administration needs to be regularly monitored to avoid any adverse clinical outcomes such as stroke and bleeding. The quality of anticoagulation control with warfarin therapy can be measured by using time in therapeutic range (TTR). This review focuses on the prevalence of AF, quality of anticoagulation control (TTR) and adverse clinical outcome in AF patients within different ethnic groups receiving warfarin therapy for stroke prevention. A literature search was conducted in Embase and PubMed using keywords of “prevalence,” “atrial fibrillation,” “stroke prevention,” “oral anticoagulants,” “warfarin,” “ethnicities,” “race” “time in therapeutic range,” “adverse clinical outcome,” “stroke, bleeding.” Articles published by 1st February 2020 were included. Forty-one studies were included in the final review consisting of AF prevalence (n = 14 studies), time in therapeutic range (n = 18 studies), adverse clinical outcome (n = 9 studies) within different ethnic groups. Findings indicate that higher prevalence of AF but better anticoagulation control among the Whites as compared to other ethnicities. Of note, non-whites had higher risk of strokes and bleeding outcomes while on warfarin therapy. Addressing disparities in prevention and healthcare resource allocation could potentially improve AF-related outcomes in minorities.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Vamos ◽  
J Oldgren ◽  
G.-B Nam ◽  
G Lip ◽  
H Calkins ◽  
...  

Abstract Background The use of antiarrhythmic drugs in patients with chronic kidney disease (CKD) is challenging due to issues with renal clearance, drug accumulation and increased proarrhythmic risks. Since CKD is a common comorbidity with atrial fibrillation (AF), it is important to establish the efficacy and safety for antiarrhythmic drug treatment in patients with CKD. Purpose To evaluate the efficacy and safety of dronedarone in patients with AF or atrial flutter (AFL) across different stages of renal impairment. Methods In this post-hoc analysis of ATHENA (NCT00174785), a randomised, double-blind trial of dronedarone 400 mg BID vs placebo in patients with AF or AFL plus additional risk factors for death and a calculated glomerular filtration rate ≥10 mL/min, the primary outcome was time to first cardiovascular (CV) hospitalisation or death. Renal function (estimated glomerular filtration rate [eGFR]) was assessed using CKD Epidemiology Collaboration equation and patients were grouped by eGFR (10–44, 45–59, ≥60 mL/min). Log-rank testing and Cox regression were used to compare time to events between treatment groups. Results In ATHENA, 43.6% of placebo and 42.2% of dronedarone patients had mild-to-moderate CKD (Table). Median time to CV hospitalisation/death was longer in all strata for dronedarone vs placebo, reaching significance in the 45–59 and ≥60 mL/min groups (Figure 1). There was a trend towards more treatment-emergent adverse events (TEAEs), deaths and discontinuations due to TEAEs in patients with eGFR 10–44 mL/min. No clear difference in safety was seen between treatment arms except for discontinuations, which were higher with dronedarone. Conclusions This analysis confirms the efficacy of dronedarone, demonstrated in ATHENA, across different stages of renal impairment. Further assessment of safety will require larger populations of patients with CKD. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Sanofi


2017 ◽  
Vol 69 (6) ◽  
pp. 752-753 ◽  
Author(s):  
Anders Nissen Bonde ◽  
Gregory Y.H. Lip ◽  
Anne-Lise Kamper ◽  
Laila Staerk ◽  
Christian Torp-Pedersen ◽  
...  

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