Direct Oral Anticoagulants and Risk of Acute Kidney Injury in Patients With Atrial Fibrillation

The relationship between kidneys and anticoagulation is complex, especially after introduction of the direct oral anticoagulants (DOAC). It is recently growing evidence of an anticoagulant-related nephropathy (ARN), a form of acute kidney injury caused by excessive anticoagulation. The pathogenesis of kidney damage in this setting is multifactorial, and nowadays, there is no established treatment. We describe a case of ARN, admitted to our Nephrology Unit with a strong suspicion of ANCA-associated vasculitis due to gross haematuria and haemoptysis; the patient was being given dabigatran. Renal biopsy excluded ANCA-associated vasculitis and diagnosed a red blood cell cast nephropathy superimposed to an underlying IgA nephropathy. Several mechanisms are possibly responsible for kidney injury in ARN: tubular obstruction, cytotoxicity of heme-containing molecules and free iron, and activation of proinflammatory/proﬁbrotic cytokines. Therefore, the patient was given a multilevel strategy of treatment. A combination of reversal of coagulopathy (i.e., withdrawal of dabigatran and infusion of its specific antidote) along with administration of fluids, sodium bicarbonate, steroids, and mannitol resulted in conservative management of AKI and fast recovery of renal function. This observation could suggest a prospective study aiming to find the best therapy of ARN.

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Non‐Vitamin K Antagonist Oral Anticoagulants Provide Less Adverse Renal Outcomes Than Warfarin In Non‐Valvular Atrial Fibrillation: A Systematic Review and MetaAnalysis

Journal of the American Heart Association ◽

10.1161/jaha.120.019609 ◽

2021 ◽

Author(s):

Patita Sitticharoenchai ◽

Kullaya Takkavatakarn ◽

Smonporn Boonyaratavej ◽

Kearkiat Praditpornsilpa ◽

Somchai Eiam‐Ong ◽

...

Keyword(s):

Atrial Fibrillation ◽

Acute Kidney Injury ◽

Renal Disease ◽

End Stage Renal Disease ◽

Oral Anticoagulants ◽

Kidney Injury ◽

Incidence Rates ◽

Renal Outcomes ◽

Stage Renal Disease ◽

End Stage

Background Non‐vitamin K antagonist oral anticoagulants (NOACs) have better pharmacologic properties than warfarin and are recommended in preference to warfarin in most patients with non‐valvular atrial fibrillation. Besides lower bleeding complications, other advantages of NOACs over warfarin particularly renal outcomes remain inconclusive. Methods and Results Electronic searches were conducted through Medline, Scopus, Cochrane Library databases, and ClinicalTrial.gov. Randomized controlled trials and observational cohort studies reporting incidence rates and hazard ratio (HR) of renal outcomes (including acute kidney injury, worsening renal function, doubling serum creatinine, and end‐stage renal disease) were selected. The random‐effects model was used to calculate pooled incidence and HR with 95% CI. Eighteen studies were included. A total of 285 201 patients were enrolled, 118 863 patients with warfarin and 166 338 patients with NOACs. The NOACs group yielded lower incidence rates of all renal outcomes when compared with the warfarin group. Patients treated with NOACs showed significantly lower HR of risk of acute kidney injury (HR, 0.70, 95% CI, 0.64–0.76; P <0.001), worsening renal function (HR, 0.83; 95% CI, 0.73–0.95; P =0.006), doubling serum creatinine (HR, 0.58; 95% CI, 0.41–0.82; P =0.002), and end‐stage renal disease (HR, 0.82; 95% CI, 0.78–0.86; P <0.001). Conclusions In non‐valvular atrial fibrillation, patients treated with NOACs have a lower risk of both acute kidney injury and end‐stage renal disease when compared with warfarin.

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The Risk of Acute Kidney Injury with Oral Anticoagulants in Elderly Adults with Atrial Fibrillation

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.05920421 ◽

2021 ◽

pp. CJN.05920421

Author(s):

Ziv Harel ◽

Eric McArthur ◽

Nivethika Jeyakumar ◽

Manish Sood ◽

Amit Garg ◽

...

Keyword(s):

Atrial Fibrillation ◽

Acute Kidney Injury ◽

Lower Risk ◽

Propensity Scores ◽

Proportional Hazards ◽

Oral Anticoagulants ◽

Kidney Injury ◽

International Normalized Ratio ◽

Population Based ◽

Cox Proportional Hazards

Background: Anticoagulation with either with a vitamin K antagonist or a direct oral anticoagulant (DOAC) may be associated with acute kidney injury (AKI). Our objective was to assess the risk of AKI among elderly individuals with atrial fibrillation (AF) newly prescribed a DOAC (dabigatran, rivaroxaban, or apixaban) versus warfarin. Methods: A population-based cohort study of 20,683 outpatients in Ontario, Canada, ≥66 years, with atrial fibrillation who were prescribed warfarin, dabigatran, rivaroxaban or apixaban between 2009- 2017. Inverse probability of treatment weighting based on derived propensity scores for the treatment with each DOAC was used to balance baseline characteristics among patients receiving each of the three DOACs, compared to warfarin. Cox proportional hazards regression was performed in the weighted population to compare the association between the prescribed anticoagulant and the outcomes of interest. The exposure was an outpatient prescription of warfarin, or one of the DOACs. The primary outcome was a hospital encounter with AKI, defined using KDIGO thresholds. Prespecified subgroup analyses were conducted by estimated glomerular filtration rate (eGFR) category, and by the percentage of international normalized ratio measurements in range, a validated marker of anticoagulation control. Results: : Each DOAC was associated with a significantly lower risk of AKI compared to warfarin (weighted HR 0.65; 95% CI 0.53 to 0.80 for dabigatran, weighted HR 0.85; 95% CI 0.73 to 0.98 for rivaroxaban; and weighted HR 0.81; 95% CI 0.72 to 0.93 for apixaban). In subgroup analysis, the lower risk of AKI associated with each DOAC was consistent across each eGFR strata. The risk of AKI was significantly lower among users of each of the DOACs compared to warfarin users who had a percentage of international normalized ratio measurements ≤56.1%. Conclusions: DOACs were associated with a lower risk of AKI compared to warfarin.

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Idarucizumab for the treatment of dabigatran-related nephropathy

Clinical Kidney Journal ◽

10.1093/ckj/sfaa030 ◽

2020 ◽

Author(s):

Ammar Alsamarrai ◽

Nicola Eaddy ◽

Elizabeth Curry

Keyword(s):

Acute Kidney Injury ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Specific Treatment ◽

Kidney Injury ◽

Clinical Syndrome ◽

Reversal Agent ◽

Macroscopic Haematuria ◽

Anticoagulant Reversal

Abstract Anticoagulant-related nephropathy (ARN) is a clinical syndrome of acute kidney injury in patients taking vitamin K antagonists or direct oral anticoagulants. It is associated with increased mortality and there is no specific treatment. We report the case of a 78-year-old man on dabigatran who developed macroscopic haematuria and acute kidney injury 2 weeks after mitral valve repair, reaching a peak creatinine of 415 µmol/L from a normal baseline, which was successfully treated with one course of idarucizumab. This case illustrates the efficacy of an anticoagulant reversal agent for the treatment of ARN.

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Comparative Risk of Acute Kidney Injury with Oral Anticoagulant Use Among Patients with Nonvalvular Atrial Fibrillation

Blood ◽

10.1182/blood.v130.suppl_1.700.700 ◽

2017 ◽

Vol 130 (Suppl_1) ◽

pp. 700-700 ◽

Cited By ~ 1

Author(s):

Adi J. Klil-Drori ◽

Laurent Azoulay ◽

Rui Nie ◽

Christel Renoux ◽

Sharon J. Nessim ◽

...

Keyword(s):

Atrial Fibrillation ◽

Acute Kidney Injury ◽

Risk Score ◽

Research Funding ◽

Disease Risk ◽

Oral Anticoagulants ◽

Kidney Injury ◽

Nonvalvular Atrial Fibrillation ◽

Disease Risk Score ◽

Comparative Risk

Abstract Background: Acute kidney injury (AKI) is common in patients with nonvalvular atrial fibrillation (NVAF) taking oral anticoagulants (OAC), especially in those with underlying chronic kidney disease (CKD). However, little is known on the comparative risk of AKI with the use of different OAC, including the direct acting oral anticoagulants (DOACs). Methods: We conducted a population-based cohort study using the administrative healthcare databases of Quebec, Canada. Patients with NVAF who were new users of oral anticoagulants between 2011 and 2014 were followed for hospitalized AKI, stratified by CKD status. Hazard ratios (HR) and corresponding 95% CI for hospitalized AKI with the use of dabigatran, rivaroxaban, and apixaban versus warfarin and versus each other in pairwise analyses, were assessed using Cox proportional hazards models. Estimates were stratified by the deciles of a disease risk score for AKI obtained from a historic cohort of 25,513 warfarin users with NVAF. The disease risk score included important demographic and clinical covariates weighted by their association with AKI. Results: Our cohort of 26,357 patients with NVAF included 22,084 without, and 4273 with CKD. The rates of AKI hospitalization were 3.2 (95% CI 2.9-3.4) and 16.5 (95% CI 15.3-17.9) per 100 person-years, respectively. Among patients without CKD, apixaban (HR, 0.25; 95% CI, 0.14-0.44), rivaroxaban (HR, 0.50; 95% CI, 0.40-0.64), and dabigatran (HR, 0.68; 95% CI 0.57-0.81) were associated with a decreased risk of AKI compared with warfarin (Table 1). Similar findings were observed in the CKD cohort (Table 2). Compared with apixaban, dabigatran was associated with increased AKI risk in patients without (HR, 2.58; 95% CI, 1.42-4.67) and with (HR, 2.08; 95% CI, 1.01-4.26) CKD, as was rivaroxaban (without CKD - HR, 2.29 [95% CI, 1.24-4.20]; with CKD - HR, 1.98 [95% CI, 0.95-4.11]). Rivaroxaban was associated with decreased risk of AKI in patients without CKD (HR, 0.76; 95% CI, 0.58-0.99), compared with dabigatran. Conclusions: Use of all DOACs was associated with decreased risk of AKI compared with warfarin. Apixaban was associated with the lowest comparative risk of AKI among DOACs, and rivaroxaban was suggested to be more protective than dabigatran in patients without CKD. While these findings await further confirmation, worsening renal function while on DOAC treatment has been associated with increased risk of major bleeding. Thus, suggested differences in the renal safety of DOACs should be incorporated in informed prescription and monitoring of these drugs. Disclosures Renoux: Bayer Pharmaceuticals: Research Funding; Canadian Foundation for Innovation: Research Funding.

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Faculty Opinions recommendation of Efficacy and Harms of Direct Oral Anticoagulants in the Elderly for Stroke Prevention in Atrial Fibrillation and Secondary Prevention of Venous Thromboembolism: Systematic Review and Meta-Analysis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725514028.793512947 ◽

2016 ◽

Author(s):

Nanette Wenger

Keyword(s):

Atrial Fibrillation ◽

Systematic Review ◽

Venous Thromboembolism ◽

Secondary Prevention ◽

Stroke Prevention ◽

Meta Analysis ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

The Elderly

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A Systematic Review of the Efficacy and Safety of Direct Oral Anticoagulants in Atrial Fibrillation Patients with Diabetes Using a Risk Index

Journal of Clinical Medicine ◽

10.3390/jcm10132924 ◽

2021 ◽

Vol 10 (13) ◽

pp. 2924

Author(s):

Domenico Acanfora ◽

Marco Matteo Ciccone ◽

Valentina Carlomagno ◽

Pietro Scicchitano ◽

Chiara Acanfora ◽

...

Keyword(s):

Diabetes Mellitus ◽

Atrial Fibrillation ◽

Major Bleeding ◽

Oral Anticoagulants ◽

Risk Index ◽

Direct Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Efficacy Rate ◽

Cochrane Central Register ◽

Efficacy And Safety

Diabetes mellitus (DM) represents an independent risk factor for chronic AF and is associated with unfavorable outcomes. We aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF), with and without diabetes mellitus (DM), using a new risk index (RI) defined as: RI =Rate of EventsRate of Patients at Risk. In particular, an RI lower than 1 suggests a favorable treatment effect. We searched MEDLINE, MEDLINE In-Process, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials. The risk index (RI) was calculated in terms of efficacy (rate of stroke/systemic embolism (stroke SEE)/rate of patients with and without DM; rate of cardiovascular death/rate of patients with and without DM) and safety (rate of major bleeding/rate of patients with and without DM) outcomes. AF patients with DM (n = 22,057) and 49,596 without DM were considered from pivotal trials. DM doubles the risk index for stroke/SEE, major bleeding (MB), and cardiovascular (CV) death. The RI for stroke/SEE, MB, and CV death was comparable in patients treated with warfarin or DOACs. The lowest RI was in DM patients treated with Rivaroxaban (stroke/SEE, RI = 0.08; CV death, RI = 0.13). The RIs for bleeding were higher in DM patients treated with Dabigatran (RI110 = 0.32; RI150 = 0.40). Our study is the first to use RI to homogenize the efficacy and safety data reported in the DOACs pivotal studies against warfarin in patients with and without DM. Anticoagulation therapy is effective and safe in DM patients. DOACs appear to have a better efficacy and safety profile than warfarin. The use of DOACs is a reasonable alternative to vitamin-K antagonists in AF patients with DM. The RI can be a reasonable tool to help clinicians choose between DOACs or warfarin in the peculiar set of AF patients with DM.

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Delayed lumbar plexus palsy due to giant psoas hematoma associated with vertebral compression fracture and direct oral anticoagulants: a case report

BMC Musculoskeletal Disorders ◽

10.1186/s12891-021-04267-9 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Chikako Ishii ◽

Miki Komatsu ◽

Kota Suda ◽

Masahiko Takahata ◽

Satoko Matsumoto Harmon ◽

...

Keyword(s):

Computed Tomography ◽

Atrial Fibrillation ◽

Cerebral Infarction ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Lumbar Plexus ◽

Vertebral Compression Fractures ◽

Minimal Risk ◽

Motor Weakness ◽

Segmental Artery

Abstract Background Osteoporotic vertebral compression fractures (VCFs) are commonly observed in elderly people and can be treated by conservatively with minimal risk of complications in most cases. However, utilization of direct oral anticoagulants (DOACs) increases the risks of secondary hematoma even after insignificant trauma. The use of DOACs increased over the past decade because of their approval and recommendation for both stroke prevention in non-valvular atrial fibrillation and treatment of venous thromboembolism. It is well known that DOACs are safer anticoagulants than warfarin in terms of major and nonmajor bleeding; however, we noted an increase in the number of bleeding events associated with DOACs that required medical intervention. This report describes the first case of delayed lumbar plexus palsy due to DOAC-associated psoas hematoma after VCF to draw attention to potential risk of severe complication associated with this type of common and stable trauma. Case presentation An 83-year-old man presented with his left inguinal pain and inability to ambulate after falling from standing position and was prescribed DOACs for chronic atrial fibrillation. Computed tomography angiography revealed a giant psoas hematoma arising from the ruptured segmental artery running around fractured L4 vertebra. Because of motor weakness of his lower limbs and expansion of psoas hematoma revealed by contrast computed tomography on day 8 of his hospital stay, angiography aimed for transcatheter arterial embolization was tried, but could not demonstrate any major active extravasation; therefore spontaneous hemostasis was expected with heparin replacement. On day 23 of his stay, hematoma turned to decrease, but dysarthria and motor weakness due to left side cerebral infarction occurred. His pain improved and bone healing was achieved about 2 months later from his admission, however the paralysis of the left lower limb and aftereffects of cerebral infarction remained after 1 year. Conclusion In patients using DOACs with multiple risk factors, close attention must be taken in vertebral injury even if the fracture itself is a stable-type such as VCF, because segmental artery injury may cause massive psoas hematoma followed by lumbar plexus palsy and other complications.

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