Atrial fibrillation and chronic kidney disease: A review of options for therapeutic anticoagulation to reduce thromboembolism risk

Abstract

Atrial fibrillation and chronic kidney disease (CKD) commonly occur together, which poses a therapeutic dilemma due to increased risk of both systemic thromboembolism and bleeding. Chronic kidney disease also has implications for medication selection. The objective of this review is to evaluate the options for anticoagulation for thromboembolism prevention in patients with atrial fibrillation and chronic kidney disease. We searched PubMed for studies of patients with atrial fibrillation and CKD on warfarin or a direct oral anticoagulant (DOAC) for thromboembolism prevention through January 1 2018, in addition to evaluating major trials evaluating DOACs and warfarin use as well as society guidelines. For patients with mild to moderate chronic kidney disease, primarily observational data supports the use of warfarin, and high quality trial data and meta‐analyses support the use and possible superiority of DOACs. For patients with severe chronic kidney disease, there are limited data on warfarin which supports its use, and data for DOACs is limited primarily to pharmacologic studies which support dose reductions but lack information on patient outcomes. For patients with end‐stage renal disease, studies on warfarin are conflicting, but the majority suggest a lack of benefit and possible harm; studies in DOACs are very limited, but apixaban is the least renally cleared and may be both safe and effective. In conclusion, warfarin or DOACs may be used based on the degree of severity of chronic kidney disease, but further study in needed in patients with end‐stage renal disease.

Efficacy and safety of direct oral anticoagulants in patients with atrial fibrillation and chronic kidney disease

“…Patients in our study were primarily taking (A) (B) apixaban, which has the best risk benefit profile of the DOACs, and the most evidence for use in advanced kidney disease. 40 Additionally, despite using a primarily ambulatory population, our study sample had a high prevalence of thromboembolic risk factors as well as bleeding risk. Finally, we found similar rates of stroke and systemic embolism as those found with DOAC use in the major DOAC trials (Figure 1, Supporting Information Table S1), [9][10][11][12] which support our study design and methodology.…”

“…Our study included patients with both CKD IV and V, as well as patients on hemodialysis and peritoneal dialysis, providing data on patients who were excluded from clinical trials. Patients in our study were primarily taking apixaban, which has the best risk benefit profile of the DOACs, and the most evidence for use in advanced kidney disease . Additionally, despite using a primarily ambulatory population, our study sample had a high prevalence of thromboembolic risk factors as well as bleeding risk.…”

“…Our study suggests that DOACs appear to be as safe and effective in patients with advanced kidney disease, but further study is needed in the form of well‐designed, prospective, randomized controlled trials with long‐term follow up, and an emphasis on dialysis patients. In addition, future studies may focus primarily on apixaban, given its favorable efficacy and safety profile, its low degree of renal clearance, and prior studies supporting its potential efficacy in dialysis patients …”

“…In addition, future studies may focus primarily on apixaban, given its favorable efficacy and safety profile, its low degree of renal clearance, and prior studies supporting its potential efficacy in dialysis patients. 40…”

Risks of anticoagulation in patients with chronic kidney disease and atrial fibrillation: More than just bleeding?

“…This complicates the assessment of the risk/benefit ratio for initiating anticoagulation in individuals with CKD—particularly those with end‐stage kidney disease and atrial fibrillation, for whom there is weak evidence supporting a clinical benefit from anticoagulation but a clear signal for excess risk of death and major bleeding . As a result, current recommendations for initiating anticoagulation in patients with end‐stage kidney disease and atrial fibrillation at high risk for thromboembolism are equivocal, with most guidelines leaving it up to clinical judgement (and many clinicians in turn deciding to forego anticoagulation). There is much stronger evidence for a net clinical benefit of anticoagulation in CKD patients not yet on dialysis who have atrial fibrillation and are at high risk for thromboembolism, supporting the use of anticoagulation in these patients despite their excess risk of major bleeding.…”