A systematic review of direct oral anticoagulant use in chronic kidney disease and dialysis patients with atrial fibrillation

Feldberg, Jordanne; Patel, Param; Farrell, Ashley; Sivarajahkumar, Sylvia; Cameron, Karen; Ma, Jennifer; Battistella, Marisa

doi:10.1093/ndt/gfy031

Cited by 75 publications

(59 citation statements)

References 44 publications

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“…In hemodialysis patients, there was no difference in stroke outcomes between dabigatran and warfarin. In this group of patients, dabigatran was associated with an increased major bleeding risk [34,35].…”

Section: Dabigatranmentioning

confidence: 81%

“…It is worth noting that the occurrence of embolic stroke was 9.0/100 patient-years in comparison to warfin (5.8) and the occurrence of arterial embolism was 1.6/100 patient-years in dabigatran group and 0.7 in the warfarin one [34]. Feldberg et al [35] in their systematic review, which included 10 studies, underlined that for moderate CKD patients (eGFR 30-60 mL/min/1.73 m 2 ) there was no difference in stroke outcomes between dabigatran 110 mg [HR 0.78, 95% CI 0.51-1.21] and warfarin. However, the risk of stroke or systemic embolism was significantly reduced with dabigatran 150 mg versus warfarin (HR 0.55, 95% CI 0.34-0.89).…”

Section: Dabigatranmentioning

confidence: 96%

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The use of anticoagulants in chronic kidney disease: Common point of view of cardiologists and nephrologists

Domienik‐Karłowicz¹,

Tronina

Lisik³

et al. 2020

Cardiol J.

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In patients diagnosed with chronic kidney disease (CKD), atrial fibrillation (AF) is associated with an increased risk of thromboembolism and stroke. Moreover, patients with CKD-especially those in end-stage renal disease-also present an increased risk of bleeding. Oral anticoagulation is the most effective form of thromboprophylaxis in patients with AF and an increased risk of stroke. However, the underuse of these drugs was observed, mainly due to safety reasons and restricted evidence on efficacy. Much evidence suggests that non-vitamin K-dependent oral anticoagulant agents significantly reduce the risk of stroke, intracranial hemorrhage, and mortality, with lower to similar major bleeding rates compared with vitamin K antagonists, such as warfarin, in normal renal function subjects. Thus, they are currently recommended for that group of patients. However, their metabolism is largely dependent on the kidneys for elimination, and current knowledge in this area is limited due to patients with a decreased glomerular filtration rate are usually excluded from clinical trials. The present review article focuses on currently available data on oral anticoagulants in patients with moderate to advanced chronic kidney disease and those with end stage renal disease.

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Section: Dabigatranmentioning

confidence: 81%

Section: Dabigatranmentioning

confidence: 96%

The use of anticoagulants in chronic kidney disease: Common point of view of cardiologists and nephrologists

Domienik‐Karłowicz¹,

Tronina

Lisik³

et al. 2020

Cardiol J.

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“…Patients on HD have a clearly increased risk of bleeding caused by uremia-associated platelet dysfunction, other defects of hemostasis, and anticoagulation with heparin [20][21][22]. Approximately 8-36% of dialysis patients are treated with oral anticoagulants or antiplatelet agents for cardiocerebrovascular complications [23,24] with 0.05-0.22 events/year of major bleeding rates worldwide [25,26]. In addition, perioperative management of HD patients for surgery, e.g., for parathyroidectomy, vascular access surgery, trauma or renal transplantation, has become more and more routine with a systemic anticoagulation contraindication [27].…”

Section: Discussionmentioning

confidence: 99%

Modified regional citrate anticoagulation is optimal for hemodialysis in patients at high risk of bleeding: A prospective randomized study of three anticoagulation strategies

Lin

Song

Huang

et al. 2019

Preprint

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Background The recommended regular saline flushing presents clinical ineffectiveness for patients at high risk of bleeding with heparin contraindication. Regional citrate anticoagulation (RCA) has been used in a Ca2+ containing dialysate with prefilter citrate in one arm (RCA-one). The anticoagulation effect was not realized, and up to 40% resulted in serious clotting in the venous expansion chamber.We innovatively transferred one-quarter of the TSC from the prefilter to the postfilter based on RCAone, which is called RCA-two in this trial. The objective of this study was to compare the efficacy and safety of RCA-two with either saline flushing or RCA-one in HD patients with a high bleeding risk.Method In this investigator-initiated, multicenter, placebo-controlled, prospective, randomized clinical trial, 52 patients (77 sessions) were randomized to the RCA-two and RCA-one group in part one trial, and 45 patients (64 sessions) were randomized to the RCA-two and Saline group in part two trial.Serious clotting events, adverse events and blood analyses were recorded. Results The primary outcome, Serious clotting events in the RCA-two group were significantly lower than that in the RCAone and Saline group (7.89% vs. 30.77%, P = 0.011; 3.03% vs. 54.84%, P < 0.001, respectively). The median circuit survival time was 240 min (IQR 240 to 240) in the RCA-two group, which was significantly longer than 230 min (IQR 155 to 240, P < 0.001) in the RCA-one group and 210 min (IQR 135 to 240 P = 0.003) in the Saline group. The majority of the AEs were hypotension, hypoglycemia and chest tightness, most of which were mild in intensity. Eight patients (20.51%) in the RCA-one group, 4 patients (12.90%) in the Saline group and 10 patients (26.31%) in the RCA-two group, P>0.05. Conclusions Our data demonstrated that the modified anticoagulation protocol is more effective and feasible during hemodialysis therapy for patients at high risk of bleeding. Trial registration: GDREC, GDREC2017250H. Registered 2th February 2018-Retrospectively registered.

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“…A recent systematic review concluded that in HD patients, compared to warfarin there was an increased risk of major bleeding with rivaroxaban (RR, 1.45; 95% CI, 1.09-1.93) and dabigatran (RR, 1.76; 95% CI, 1.44-2.15), while there was no difference between apixaban and warfarin. 65 No significant differences in stroke outcomes were seen between oral anticoagulants (apixaban, rivaroxaban, dabigatran, and warfarin).…”

Section: Safe T Y Con Cern S With Warfarin V Er Sus N Oac Smentioning

confidence: 97%

“…Two subsequent meta‐analyses, which included smaller observational studies, found that apixaban was associated with less major bleeding in HD patients with NVAF than warfarin with similar efficacy in prevention of stroke and systemic embolism. A recent systematic review concluded that in HD patients, compared to warfarin there was an increased risk of major bleeding with rivaroxaban (RR, 1.45; 95% CI, 1.09‐1.93) and dabigatran (RR, 1.76; 95% CI, 1.44‐2.15), while there was no difference between apixaban and warfarin . No significant differences in stroke outcomes were seen between oral anticoagulants (apixaban, rivaroxaban, dabigatran, and warfarin).…”

Section: Safety Concerns With Warfarin Versus Noacsmentioning

confidence: 99%

Warfarin in nonvalvular atrial fibrillation—Time for a change?

Reilly

Jain

2019

Seminars in Dialysis

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Warfarin is the most commonly prescribed anticoagulant in hemodialysis (HD) patients with nonvalvular atrial fibrillation (NVAF). Recent trends show that Nephrologists are increasingly prescribing novel oral anticoagulants, despite the fact that no randomized clinical trials have been conducted in dialysis patients. Difficulties maintaining international normalized ratio in the therapeutic range, increased risk of intracranial hemorrhage and concerns regarding warfarin‐induced vascular calcification and calciphylaxis may be responsible. Anticoagulation quality is poor in HD patients. A variety of factors contribute to this: increased antibiotic exposure; comorbid illness; decreased adherence and vitamin K deficiency. Attempts to address this with standardized protocols have been uniformly unsuccessful. In nonadherent patients, thrice weekly observed therapy improved quality. Low‐dose vitamin K supplementation improves time in the therapeutic range (TTR) in those with normal kidney function and should be studied in HD patients given their high frequency of vitamin K deficiency. Vascular and valvular calcification associated with warfarin could result from reduced carboxylation of matrix Gla protein (MGP), a well‐known inhibitor of vascular calcification. Multiple observational studies also link calciphylaxis to warfarin; warfarin‐induced hypercoagulability and decreased carboxylation of MGP could explain this. A large observational study, two meta‐analyses, and a systematic review in HD patients with NVAF showed reduced bleeding with apixaban compared to warfarin with similar efficacy in reducing stroke and systemic embolism. Given these results, apixaban is a reasonable alternative to warfarin for anticoagulation of HD patients with NVAF, especially in those with low TTR, until data from randomized clinical trials become available.

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A systematic review of direct oral anticoagulant use in chronic kidney disease and dialysis patients with atrial fibrillation

Abstract: Clinicians should continue to weigh the risk of stroke versus bleeding before prescribing DOACs in the CKD and dialysis population.

Cited by 75 publications

References 44 publications

The use of anticoagulants in chronic kidney disease: Common point of view of cardiologists and nephrologists

The use of anticoagulants in chronic kidney disease: Common point of view of cardiologists and nephrologists

Modified regional citrate anticoagulation is optimal for hemodialysis in patients at high risk of bleeding: A prospective randomized study of three anticoagulation strategies

Warfarin in nonvalvular atrial fibrillation—Time for a change?

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