Elsevier

International Journal of Cardiology

Volume 323, 15 January 2021, Pages 90-99
International Journal of Cardiology

Oral anticoagulation and cardiovascular outcomes in patients with atrial fibrillation and chronic kidney disease in Asian Population, Data from the COOL-AF Thailand registry

https://doi.org/10.1016/j.ijcard.2020.08.068Get rights and content

Highlights

  • AF patients with CKD had higher CHA2DS2-VASc score and HASBLED score.

  • CKD patients carried significant risks of stroke/TIA, major bleeding and death.

  • There was no benefit of OAC therapy for ischemic stroke/TIA reduction but clearly increased major bleeding.

  • The trend towards lower ischemic stroke/TIA risk was noticed in patients who were prescribed NOAC.

  • NOACs seemed to provide much greater net clinical benefit when compared to warfarin

Abstract

Background and objectives

Patients with AF and chronic kidney disease(CKD) encountered increased risks of stroke, bleeding, morbidity, and overall mortality. Oral anticoagulation in these populations definitely enhances major bleeding but the benefit of stroke reduction remained inconclusive.The aim of this study is to evaluate the effect of oral anticoagulation (OAC) on the 2-year cardiovascular outcomes in patients with AF and CKD.

Method

NVAF patients were consecutively enrolled from 27 hospitals located all across Thailand.Baseline demographic and clinical data were collected within 6 months from enrollment.GFR was calculated using CKD-EPI formula. CKD patients were defined as GFR less than 60 mL/min/1.73 m2 according to KDOQI of the National Kidney Foundation. Clinical outcomes included ischemic stroke or transient ischemic attack (TIA) and major bleeding.

Results

At 25.7 ± 10.6 months of follow up, we identified 2538 patients with complete renal follow-up data. Among these were 1594 patients with CKD (stage 3–5) and 944 patients without CKD. The rate of ischemic stroke in patients with and without CKD were 3.7% and 1.7% respectively (p = 0.004),the rate of major bleeding was 5.6 and 3.5% accordingly (p = 0.015) and, likewise, the death rate was substantially high in patients with CKD (10.0% and 6.5%, p = 0.02). The rate of ischemic stroke/TIA in patients with CKD who were and were not on OAC did not differ significantly, 3.6% and 4.2% respectively (p = 0.602). NOAC and warfarin did not differ significantly in the propensity score-matched rate of both ischemic stroke/TIA (0 and 1.2%, p = 0.554) and major bleeding (3.3% and 7.4%, p = 0.122).The net clinical benefit of NOAC over warfarin was 2.153 per 100-patient years.

Conclusions

COOL AF registry demonstrated that AF patients with CKD had increased risks of ischemic stroke/TIA, major bleeding and death. The benefit of stroke/TIA reduction was not significantly evident for either warfarin or NOAC. However, NOAC was associated with the positive net clinical benefit over no OAC.

Introduction

Atrial fibrillation (AF) was a common problem in clinical practice. The prevalence of AF was 1–4% in western countries [1,2] and 0.5–2% in Asia-pacific countries [3].

Chronic kidney disease (CKD) was also prevalent and posed a challenging managing problem.These two diseases often coexisted and were commonly found in clinical practice because they both shared common risk factors, such as elderly, hypertension, diabetes, smoking and heart failure. In patients with AF and CKD, evidences suggested that there were increasing risks of stroke, morbidity, and overall mortality. Moreover, incidence of bleeding was also increasing in these population [[4], [5], [6], [7]] Data from clinical trials from the RE-LY study (Dabigatran), ROCKET-AF(Rivaroxaban), ARISTOTLE (Apixaban) and ENGAGE TIMI - 48 (Edoxaban) demonstrated that the rate of stroke and systemic thromboembolism per year in patients with chronic kidney disease (GFR < 50 ml/min) were 1.53,2.32,2.11 and 2.30% and the rate of major bleeding were 5.50,4.49,3.21 and 4.0% respectively [[8], [9], [10]] These number doubled the risk of stroke and systemic thromboembolism and almost quadruple the risk of bleeding in comparison to patients without chronic kidney disease in contemporary data. Data concerning the effectiveness of the novel oral anticoagulants vs. warfarin and also vs. aspirin in patients with CKD (moderate / pre-terminal CKD) and AF showed a very low level of heterogeneity was found among the three selected trials (I2 = 0%) showing an overall benefit of the non vitamin K oral anticoagulants compared to warfarin (HR = 0.80; 95%CI 0.66–0.96; P = 0.02) [11]. The excessive bleeding risk maybe one of the contributing factors that explained why physicians were reluctant to prescribe oral anticoagulation(OAC) to AF patients with chronic kidney disease. Asian population also demonstrated a higher risk of warfarin-related intracerebral hemorrhage and bleeding-related complications. Moreover, data from the recent GARFIELD-AF study suggested that the effect of moderate-to-severe CKD on mortality was even greater in patients from Asia than the rest of the world [12].

COOL AF is a nationwide multicenter registry of patients with nonvalvular atrial fibrillation (NVAF). The study included data from 27 hospitals across all regions in Thailand. Data were recorded in a case record form and then transferred into a web-based system. The aim of this study is to evaluate the effect of oral anticoagulation on the 2-year cardiovascular outcomes in patients with atrial fibrillation and chronic kidney disease.

Section snippets

Study population and data collection

NVAF patients were consecutively enrolled from 27 hospitals located all across Thailand. Thirteen of those centers are university hospitals, and ten are regional or general hospitals. The protocol for this study was approved by the institutional review boards (IRBs) of the Thailand Ministry of Public Health and IRB of each participating hospital namely Buddhachinaraj Hospital, Central Chest Institute of Thailand, Charoen Krung Pracha Rak Hospital, Chiangrai Prachanukroh Hospital, Chonburi

Results

At the beginning of the study,we enrolled 3461 patients of the entire COOL AF cohort study. At 25.7 ± 10.6 months of follow up, we identified 2538 patients with complete renal follow-up data(Table 1). Among these were 1594 patients with CKD (stage 3–5) and 944 patients without significant CKD and normal GFR. Compared with patients without CKD, AF patients with CKD were more likely to be older, male, and have more extensive medical comorbidities, including coronary artery disease, hypertension,

Discussion

In COOL-AF registry analysis of patients with AF and CKD (stage3–5), we demonstrated that more than half of the patients had CKD of stage 3 and above. Patients with CKD and concomitant AF were more likely to be older, male, and have multiple medical comorbidities, including coronary artery disease, hypertension, diabetes, higher CHA2DS2-VASc and HAS-BLED score as in contemporary real world data. It was clearly evident that CKD patients, from our registry, had higher stroke/TIA and major

Conclusions

Our COOL-AF registry demonstrated that there were increased risks of major cardiovascular outcomes which were ischemic stroke/TIA, major bleeding and death in AF patients with CKD. We reported a relatively high rate of use of anticoagulant which the majority of them were warfarin. Unfortunately, the benefit of stroke reduction was not significantly evident for patients who received either warfarin or NOAC in the setting of CKD. However, we highlighted the positive net clinical benefit of NOAC

Funding disclosure

This study was funded by the Health Systems Research Institute (HSRI) (grant no. 59-053), the Heart Association of Thailand under the Royal Patronage of H.M. the King. None of the funding sources had influenced for the decision of the authors to submit this manuscript for publication.

Author statements

Thoranis Chantrarat - concept and design, data acquisition, interpretation of data, manuscript preparation, manuscript revision; and approved the submission of this manuscript for journal publication.

Rungroj Krittayapong- data acquisition, manuscript revision, data analysis and manuscript review;

All authors read and approved the final manuscript and the 2 authors contributed equally in this paper.

This statement is to certify that all authors have seen and approved the manuscript being

Declaration of Competing Interest

All authors declare no personal or professional conflicts of interest, and no financial support from the companies that produce and/or distribute the drugs, devices, or materials described in this report.

Acknowledgements

The authors gratefully acknowledge the patients that participated in this study, and Ms.Chulalak Komoltri, PhD, for assistance with statistical analysis.

References (21)

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