Apixaban for Patients With Atrial Fibrillation on Hemodialysis: A Multicenter Randomized Controlled Trial

Pokorney, Sean D.; Chertow, Glenn M.; Al‐Khalidi, Hussein R.; Gallup, Dianne; Dignacco, Pat; Mussina, Kurt; Bansal, Nisha; Gadegbeku, Crystal A.; García, David; Garonzik, Samira M.; Lópes, Renato D.; Mahaffey, Kenneth W.; Matsuda, Kelly; Middleton, John; Rymer, Jennifer A.; Sands, George H.; Thadhani, Ravi; Thomas, Kevin L.; Washam, Jeffrey B.; Winkelmayer, Wolfgang C.; Granger, Christopher B.

doi:10.1161/circulationaha.121.054990

Cited by 115 publications

(121 citation statements)

References 25 publications

(45 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…RENAL-AF (Renal Hemodialysis Patients Allocated Apixaban Versus Warfarin in Atrial Fibrillation), a US study of apixaban, was stopped early in 2019 after randomizing 154 patients because of severe recruitment problems; the results are published in this issue of Circulation . 23 In brief, the patients in the US apixaban trial were an average of 10 years younger and had a slightly lower mean CHA 2 DS 2 -VASc score of 4.0 compared with 4.5 in our trial. RENAL-AF found no significant differences between apixaban and VKA regarding safety and efficacy, with 1-year Kaplan-Meier estimates for bleeding of 32% for apixaban and 26% for VKA.…”

Section: Discussionmentioning

confidence: 58%

“…The TTR in the VKA arm was lower (50.7%) than the TTR in large NOAC trials testing anticoagulation in patients not on hemodialysis. This low TTR is a limitation of the trial but also seems to reflect the usual quality of VKA therapy in patients with AF on hemodialysis because it is comparable to the TTR in RENAL-AF (44%), 23 the Belgian trial (48%), 24 and other reports of VKA (Table 3). Thus, VKA therapy seems to be difficult to deliver in patients on hemodialysis despite regular visits with coagulation checks during hemodialysis sessions, as also observed in the 2 other randomized trials.…”

Section: Discussionmentioning

confidence: 82%

“…Small differences in bleeding events are most likely attributable to chance in addition to potential differences between treatment with 2.5 mg and 5 mg apixaban BID in the US trial. 23 The pharmacodynamics data reported in RENAL-AF suggest that the 2.5-mg BID dose tested in AXADIA–AFNET 8 results in plasma concentrations that are comparable to those observed in patients without kidney disease, whereas the 5-mg BID dose results in plasma concentrations comparable to those observed in patients with CKD. 23…”

Section: Discussionmentioning

confidence: 94%

“…23 The pharmacodynamics data reported in RENAL-AF suggest that the 2.5-mg BID dose tested in AXADIA–AFNET 8 results in plasma concentrations that are comparable to those observed in patients without kidney disease, whereas the 5-mg BID dose results in plasma concentrations comparable to those observed in patients with CKD. 23…”

Section: Discussionmentioning

confidence: 94%

“…Therefore, our event rates in the VKA group were markedly lower than in the Belgian trial, which may be one reason they found a significant benefit for rivaroxaban. 24 Of note, in AXADIA-AFNET 8 and in the other 2 randomized controlled trials, 23,24 the mean TTR in the VKA arm was comparable but low (50.7%, 44%, and 48%, respectively), which is lower than the TTR achieved in patients with remaining excretion by the kidneys, although patients on hemodialysis see their doctors 3 times per week. The low TTR also lends support to the use of NOACs in this population.…”

Section: Comparison With Other Trials and Studiesmentioning

confidence: 97%

See 4 more Smart Citations

A Randomized Controlled Trial Comparing Apixaban With the Vitamin K Antagonist Phenprocoumon in Patients on Chronic Hemodialysis: The AXADIA-AFNET 8 Study

Reinecke¹,

Engelbertz²,

Bauersachs

et al. 2023

Circulation

View full text Add to dashboard Cite

Background: Non-vitamin K oral anticoagulants (NOACs) have become the standard therapy for preventing stroke and ischemic thromboembolism in most patients with atrial fibrillation (AF). The effectiveness and safety of NOACs in patients on hemodialysis is not well known. Methods: From June 2017 until May 2022, the investigator-initiated, prospective, randomized, open, blinded outcome assessment 'A Safety Study Assessing Oral Anticoagulation with ApiXAban versus Vitamin K-Antagonists in Patients with Atrial Fibrillation and End-Stage Kidney Disease on Chronic HemoDIAlysis Treatment' (AXADIA) trial randomized patients with AF on chronic hemodialysis to either apixaban 2.5 mg bid or the vitamin K antagonist (VKA) phenprocoumon (INR 2.0-3.0). The composite primary safety outcome was defined by a first event of major bleeding, clinically-relevant non-major bleeding, or all-cause death. The primary efficacy outcome was a composite of ischemic stroke, all-cause death, myocardial infarction, and deep vein thrombosis and/or pulmonary embolism. Our hypothesis was that apixaban is non-inferior to VKA. Results: Thirty-nine sites randomized 97 patients (30% women, mean age 75 years, mean CHA2DS2-VASc score 4.5, baseline characteristics balanced between groups), 48 to apixaban and 49 to VKA. The median follow-up time was 429 (range 37-1,370) vs. 506 (range 101-1,379) days, respectively. Adherence to apixaban was >80% in 44 of 48 patients; the median time in therapeutic range on VKA was 50.7%. Composite primary safety outcome events occurred in 22 (45.8%) patients on apixaban and in 25 (51.0%) patients on VKA (HR 0.93, 95% CI 0.53-1.65, p(noninferiority)=0.157). Composite primary efficacy outcome events occurred in 10 (20.8%) patients on apixaban and in 15 (30.6%) patients on VKA (p=0.51, log rank). There were no significant differences regarding individual outcomes (all-cause mortality 18.8% vs. 24.5%; major bleedings 10.4% vs. 12.2%; myocardial infarctions 4.2% vs. 6.1%, respectively). Conclusions: In this randomized trial comparing apixaban and VKA in patients with AF on hemodialysis with long follow-up, no differences were observed in safety or efficacy outcomes. Even on oral anticoagulation, patients with AF on hemodialysis remain at high risk of cardiovascular events. Larger randomized trials are needed to determine the optimal anticoagulation regimen for patients with AF on hemodialysis. Clinical Trial Registration: EudraCT No. 2015-005503-84, NCT02933697

show abstract

Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 94%

Section: Comparison With Other Trials and Studiesmentioning

confidence: 97%

See 3 more Smart Citations

A Randomized Controlled Trial Comparing Apixaban With the Vitamin K Antagonist Phenprocoumon in Patients on Chronic Hemodialysis: The AXADIA-AFNET 8 Study

Reinecke¹,

Engelbertz²,

Bauersachs

et al. 2023

Circulation

View full text Add to dashboard Cite

show abstract

Efficacy and Safety Considerations With Dose-Reduced Direct Oral Anticoagulants

et al. 2022

View full text Add to dashboard Cite

IMPORTANCE Dose-reduced regimens of direct oral anticoagulants (DOACs) may be used for 2 main purposes: dose-adjusted treatment intended as full-intensity anticoagulation (eg, for stroke prevention in atrial fibrillation [AF] in patients requiring dose reduction) or low-intensity treatment (eg, extended-duration treatment of venous thromboembolism [VTE]). We reviewed randomized clinical trials (RCTs) to understand the scenarios in which dose-adjusted or low-intensity DOACs were tested and reviewed the labeled indications by regulatory authorities, using data from large registries to assess whether the use of dose-reduced DOACs in routine practice aligned with the findings of RCTs. OBSERVATIONS Among 4191 screened publications, 35 RCTs that used dose-adjusted DOACs were identified for dabigatran, apixaban, rivaroxaban, and edoxaban. Of these 35 RCTs, 29 were related to stroke prevention in AF. Efficacy and safety results for dose-adjusted DOACs in large RCTs of AF were similar to those found for full-dose DOACs. To our knowledge, dabigatran, apixaban, and rivaroxaban have not been studied as dose-adjusted therapy for acute VTE treatment. Low-intensity DOACs were identified in 37 RCTs. Low-intensity DOACs may be used for extended-duration treatment of VTE (apixaban and rivaroxaban), primary prevention in orthopedic surgeries (dabigatran, apixaban, and rivaroxaban), primary prevention in ambulatory high-risk cancer patients (apixaban and rivaroxaban) or (postdischarge) high-risk medical patients (rivaroxaban), in stable atherosclerotic vascular disease, or after a recent revascularization for peripheral artery disease in conjunction with aspirin (rivaroxaban). Minor variations exist between regulatory authorities in different regions regarding criteria for dose adjustment of DOACs. Data from large registries indicated that dose-reduced DOACs were used occasionally with doses or for clinical scenarios different from those studied in RCTs or recommended by regulatory authorities.CONCLUSIONS AND RELEVANCE Dose adjustment and low-intensity treatment are 2 different forms of dose-reduced DOACs. Dose adjustment is mostly relevant for AF and should be done based on the approved criteria. Dose adjustment of DOACs should not be used for acute VTE treatment in most cases. In contrast, low-intensity DOACs may be used for primary or secondary VTE prevention for studied and approved indications. Attention should be given to routine practice patterns to align the daily clinical practice with existing evidence of safety and efficacy.

show abstract