Title: Efficacy and safety of warfarin in patients with non-valvular atrial fibrillation and CKD G3–G5D

Journal Article · · Clinical Kidney Journal

ABSTRACT Background Observational data comparing warfarin with no treatment for patients with non-valvular atrial fibrillation (NVAF) and severely reduced glomerular filtration rate (GFR) are conflicting and randomized controlled trials (RCTs) are lacking. Most studies do not provide information on warfarin treatment quality, making them difficult to compare. Methods This national cohort study investigates the risk of ischaemic stroke and major bleeding during warfarin treatment compared with no oral anticoagulants in patients with NVAF, GFR category 3–5 (G3–G5) or on dialysis (G5D), with kidney transplant recipients excluded, between 2009 and 2018. Data extracted from high-quality Swedish national healthcare registries, including the Swedish Renal Registry, AuriculA—the Swedish national quality registry for atrial fibrillation and anticoagulation—and the Stroke Registry. Results At enrolment of 12 106 patients, 21.4% were G3, 43.5% were G4, 11.6% were G5 and 23.6% were G5D. The mean time in the therapeutic range was 70%. Warfarin compared with no treatment showed a lower risk for ischaemic stroke for G3 {hazard ratio [HR] 0.37 [95% confidence interval (CI) 0.18–0.76]}, G4 [0.53 (0.38–0.74)] and G5D [0.49 (0.30–0.79)] and an increased risk of major bleeding in G4 [HR 1.22 (1.02–1.46)], G5 [1.52 (1.15–2.01)] and G5D [1.23 (1.00–1.51)]. All-cause mortality was more than halved on warfarin compared with no treatment in all GFR categories. Conclusions Warfarin treatment is associated with a lower risk of ischaemic stroke for patients with NVAF and G3, G4 and G5D at the cost of a higher risk of major bleeding for G4–G5D. Existing observational data are conflicting, stressing the need for RCTs on warfarin compared with no treatment in G4–G5D. Awaiting RCTs, it seems reasonable to treat selected patients on dialysis and NVAF with warfarin.

Sponsoring Organization:
USDOE Office of Electricity (OE), Advanced Grid Research & Development. Power Systems Engineering Research
OSTI ID:
1870521
Journal Information:
Clinical Kidney Journal, Journal Name: Clinical Kidney Journal Journal Issue: 6 Vol. 15; ISSN 2048-8505
Publisher:
Oxford University PressCopyright Statement
Country of Publication:
Country unknown/Code not available
Language:
English

References (40)

The Swedish personal identity number: possibilities and pitfalls in healthcare and medical research journal June 2009
Systematic DOACs oral anticoagulation in patients with atrial fibrillation and chronic kidney disease: the nephrologist’s perspective journal March 2020
Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention journal July 2013
Close bidirectional relationship between chronic kidney disease and atrial fibrillation: The Niigata preventive medicine study journal October 2009
Chronic kidney disease and prevalent atrial fibrillation: The Chronic Renal Insufficiency Cohort (CRIC) journal June 2010
Patients’ time in therapeutic range on warfarin among US patients with atrial fibrillation: Results from ORBIT-AF registry journal July 2015
Comparison of the impact of atrial fibrillation on the risk of stroke and cardiovascular death in women versus men (The Copenhagen City Heart Study) journal October 2004
Chronic Kidney Disease, Time in Therapeutic Range and Adverse Clinical Outcomes in Anticoagulated Patients with Non-valvular Atrial Fibrillation: Observations from the SPORTIF Trials journal June 2016
Warfarin use and the risk of mortality, stroke, and bleeding in hemodialysis patients with atrial fibrillation journal May 2017
Net Clinical Benefit of Antithrombotic Therapy in Patients With Atrial Fibrillation and Chronic Kidney Disease journal December 2014
Oral Anticoagulation and Cardiovascular Outcomes in Patients With Atrial Fibrillation and End-Stage Renal Disease journal March 2020
Clinical Outcomes of Warfarin Initiation in Advanced Chronic Kidney Disease Patients With Incident Atrial Fibrillation journal December 2020
Improvement of anticoagulant treatment using a dynamic decision support algorithm journal March 2014
Prevalence of Atrial Fibrillation and Associated Factors in a Population of Long-Term Hemodialysis Patients journal November 2005
A Method to Determine the Optimal Intensity of Oral Anticoagulant Therapy journal January 1993
Dabigatran versus Warfarin in Patients with Atrial Fibrillation journal September 2009
Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation journal September 2011
Stroke and Bleeding in Atrial Fibrillation with Chronic Kidney Disease journal August 2012
Apixaban versus Warfarin in Patients with Atrial Fibrillation journal September 2011
Edoxaban versus Warfarin in Patients with Atrial Fibrillation journal November 2013
2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS) journal August 2020
Nomenclature for kidney function and disease—executive summary and glossary from a Kidney Disease: Improving Global Outcomes (KDIGO) consensus conference journal November 2020
Anticoagulation control in Sweden: reports of time in therapeutic range, major bleeding, and thrombo-embolic complications from the national quality registry AuriculA journal May 2011
Chronic kidney disease and arrhythmias: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference journal March 2018
Warfarin use, mortality, bleeding and stroke in haemodialysis patients with atrial fibrillation journal October 2014
Influence of sex on risk of bleeding in anticoagulated patients: a systematic review and meta-analysis journal May 2014
Sex Differences in Management and Outcome After Stroke: A Swedish National Perspective journal August 2003
2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons journal July 2019
Impact of Proteinuria and Glomerular Filtration Rate on Risk of Thromboembolism in Atrial Fibrillation: The Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study journal March 2009
Warfarin Use and the Risk for Stroke and Bleeding in Patients With Atrial Fibrillation Undergoing Dialysis journal March 2014
Time in Therapeutic Range and Outcomes After Warfarin Initiation in Newly Diagnosed Atrial Fibrillation Patients With Renal Dysfunction journal March 2017
Sex Differences in Oral Anticoagulation and Outcomes of Stroke and Intracranial Bleeding in Newly Diagnosed Atrial Fibrillation journal May 2020
Atrial fibrillation in chronic dialysis patients in the United states: risk factors for hospitalization and mortality journal January 2003
External review and validation of the Swedish national inpatient register journal June 2011
Warfarin use and stroke, bleeding and mortality risk in patients with end stage renal disease and atrial fibrillation: a systematic review and meta-analysis journal October 2016
Refining Clinical Risk Stratification for Predicting Stroke and Thromboembolism in Atrial Fibrillation Using a Novel Risk Factor-Based Approach journal February 2010
Stroke, Major Bleeding, and Mortality Outcomes in Warfarin Users With Atrial Fibrillation and Chronic Kidney Disease journal April 2016
Warfarin Use Associates with Increased Risk for Stroke in Hemodialysis Patients with Atrial Fibrillation journal August 2009
Evaluating time in therapeutic range for hemodialysis patients taking warfarin journal January 2015
Benefits and Harms of Oral Anticoagulant Therapy in Chronic Kidney Disease: A Systematic Review and Meta-analysis journal July 2019