Warfarin in nonvalvular atrial fibrillation—Time for a change?

Abstract

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.

The Effects of Warfarin and Direct Oral Anticoagulants on Systemic Vascular Calcification: A Review

“…Finally, warfarin use has been associated with the development of calciphylaxis in CKD patients in several studies [74], while this association has not been found DOAC users. In one small 2017 study, 13 of 16 patients with diagnosed calciphylaxis had stable or improved cutaneous disease after initiating either apixaban or dabigatran [75].…”

Warfarin-Induced Calcification: Potential Prevention and Treatment Strategies

“…Compared with warfarin, rivaroxaban reduced the incidence of renal failure. Reilly et al [80] believed that apixaban is an ideal drug to replace warfarin in the treatment of HD complicated with NVAF. However, although both apixaban and rivaroxaban show good pharmacokinetic characteristics in ESRD, due to the potential risk of dialysis drug accumulation and the lack of adequate understanding of their mechanism, Brancaccio et al [81] believed that neither of these two drugs could be used safely in dialysis patients.…”

Anticoagulation in Atrial Fibrillation Patients

“…Hemodialysis patients are challenging for anticoagulation, because they often are multimorbid, have extensive antibiotic exposure, and may have vitamin K deficiency. Adherence can also be especially problematic in the hemodialysis population [90].…”