In the Journals

Oral anticoagulants may be harmful in patients with AF on dialysis

Among patients with atrial fibrillation on long-term dialysis, oral anticoagulants were not associated with decreased risk for thromboembolism and some of them elevated risk for bleeding, according to a meta-analysis.

In this population, warfarin, dabigatran (Pradaxa, Boehringer Ingelheim) and rivaroxaban (Xarelto, Janssen) were associated with greater bleeding risk compared with apixaban (Eliquis, Bristol-Myers Squibb/Pfizer) and no anticoagulant.

According to the meta-analysis published in the Journal of the American College of Cardiology, apixaban and warfarin were not associated with reduced risk for ischemic stroke and/or systemic thromboembolism compared with no anticoagulant (HR for apixaban 5 mg = 0.59; 95% CI, 0.3-1.17; HR for apixaban 2.5 mg = 1; 95% CI, 0.52-1.93; HR for warfarin = 0.91; 95% CI, 0.72-1.16). According to the meta-analysis, ischemic outcomes for dabigatran and rivaroxaban were not available.

Moreover, apixaban 5 mg was associated with lower risk for all-cause mortality compared with warfarin, apixaban 2.5 mg and no anticoagulant (HR vs. warfarin = 0.65; 95% CI, 0.45-0.93; HR vs. apixaban 2.5 mg = 0.62; 95% CI, 0.42-0.9; HR vs. no anticoagulant = 0.61; 95% CI, 0.41-0.9).

In addition, researchers noted that warfarin was associated with elevated risk for major bleeding compared with apixaban 5 mg, apixaban 2.5 mg and no anticoagulant (HR vs. apixaban 5 mg = 1.41; 95% CI, 1.07-1.88; HR vs. apixaban 2.5 mg = 1.4; 95% CI, 1.07-1.82; HR vs. no anticoagulant = 1.31; 95% CI, 1.15-1.5).

“Our study did not reveal the efficacy to prevent stroke and/or systemic thromboembolism of apixaban 5 mg/2.5 mg against no anticoagulant, whereas it revealed less bleeding than warfarin,” Toshiki Kuno, MD, PhD, resident in the department of medicine at the Icahn School of Medicine at Mount Sinai, and colleagues wrote. “Moreover, apixaban 5 mg twice daily was associated with a reduction in mortality compared with no anticoagulant. Because warfarin was not associated with lower stroke and showed higher risk of bleeding, further randomized controlled trials are needed to assess the feasibility of apixaban 5 mg twice daily compared with no anticoagulant to use in patients with AF on long-term dialysis.”

Findings for dabigatran, rivaroxaban

In other findings, dabigatran and rivaroxaban were also associated with greater risk for major bleeding than apixaban and no anticoagulant.

Researchers identified 16 eligible observational studies that assessed patients with AF who were on long-term dialysis. Of these studies, two investigated the efficacy and safety of direct oral anticoagulants.

“Although these results should be interpreted cautiously because of high heterogeneity, warfarin, dabigatran and rivaroxaban might not be preferred options because of their increased risk of bleeding in patients with AF on long-term dialysis,” the researchers wrote. “Further study is warranted to establish the benefit-to-risk ratio of oral anticoagulants in patients with AF on long-term dialysis.”

Knowledge gaps in dialysis and AF

“The network meta-analysis by Kuno et al has highlighted once again the existing evidence vacuum for the provision of oral anticoagulants to dialysis recipients with nonvalvular AF. For patients and their clinicians, this is especially distressing because the stakes of providing, or withholding, oral anticoagulants are conceivably so high,” Ron Wald, MDCM, MPH, of the division of nephrology at St. Michael’s Hospital at the University of Toronto, and colleagues wrote in a related editorial. “Recently completed and ongoing trials will hopefully advance the quality of evidence in this area with the ultimate goal of resolving one of the most vexing dilemmas faced by clinicians who care for patients on maintenance dialysis.” – by Scott Buzby

Disclosures: Kuno and Wald report no relevant financial disclosures. Please see the study and editorial for all other authors’ relevant financial disclosures.

Among patients with atrial fibrillation on long-term dialysis, oral anticoagulants were not associated with decreased risk for thromboembolism and some of them elevated risk for bleeding, according to a meta-analysis.

In this population, warfarin, dabigatran (Pradaxa, Boehringer Ingelheim) and rivaroxaban (Xarelto, Janssen) were associated with greater bleeding risk compared with apixaban (Eliquis, Bristol-Myers Squibb/Pfizer) and no anticoagulant.

According to the meta-analysis published in the Journal of the American College of Cardiology, apixaban and warfarin were not associated with reduced risk for ischemic stroke and/or systemic thromboembolism compared with no anticoagulant (HR for apixaban 5 mg = 0.59; 95% CI, 0.3-1.17; HR for apixaban 2.5 mg = 1; 95% CI, 0.52-1.93; HR for warfarin = 0.91; 95% CI, 0.72-1.16). According to the meta-analysis, ischemic outcomes for dabigatran and rivaroxaban were not available.

Moreover, apixaban 5 mg was associated with lower risk for all-cause mortality compared with warfarin, apixaban 2.5 mg and no anticoagulant (HR vs. warfarin = 0.65; 95% CI, 0.45-0.93; HR vs. apixaban 2.5 mg = 0.62; 95% CI, 0.42-0.9; HR vs. no anticoagulant = 0.61; 95% CI, 0.41-0.9).

In addition, researchers noted that warfarin was associated with elevated risk for major bleeding compared with apixaban 5 mg, apixaban 2.5 mg and no anticoagulant (HR vs. apixaban 5 mg = 1.41; 95% CI, 1.07-1.88; HR vs. apixaban 2.5 mg = 1.4; 95% CI, 1.07-1.82; HR vs. no anticoagulant = 1.31; 95% CI, 1.15-1.5).

“Our study did not reveal the efficacy to prevent stroke and/or systemic thromboembolism of apixaban 5 mg/2.5 mg against no anticoagulant, whereas it revealed less bleeding than warfarin,” Toshiki Kuno, MD, PhD, resident in the department of medicine at the Icahn School of Medicine at Mount Sinai, and colleagues wrote. “Moreover, apixaban 5 mg twice daily was associated with a reduction in mortality compared with no anticoagulant. Because warfarin was not associated with lower stroke and showed higher risk of bleeding, further randomized controlled trials are needed to assess the feasibility of apixaban 5 mg twice daily compared with no anticoagulant to use in patients with AF on long-term dialysis.”

Findings for dabigatran, rivaroxaban

In other findings, dabigatran and rivaroxaban were also associated with greater risk for major bleeding than apixaban and no anticoagulant.

Researchers identified 16 eligible observational studies that assessed patients with AF who were on long-term dialysis. Of these studies, two investigated the efficacy and safety of direct oral anticoagulants.

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“Although these results should be interpreted cautiously because of high heterogeneity, warfarin, dabigatran and rivaroxaban might not be preferred options because of their increased risk of bleeding in patients with AF on long-term dialysis,” the researchers wrote. “Further study is warranted to establish the benefit-to-risk ratio of oral anticoagulants in patients with AF on long-term dialysis.”

Knowledge gaps in dialysis and AF

“The network meta-analysis by Kuno et al has highlighted once again the existing evidence vacuum for the provision of oral anticoagulants to dialysis recipients with nonvalvular AF. For patients and their clinicians, this is especially distressing because the stakes of providing, or withholding, oral anticoagulants are conceivably so high,” Ron Wald, MDCM, MPH, of the division of nephrology at St. Michael’s Hospital at the University of Toronto, and colleagues wrote in a related editorial. “Recently completed and ongoing trials will hopefully advance the quality of evidence in this area with the ultimate goal of resolving one of the most vexing dilemmas faced by clinicians who care for patients on maintenance dialysis.” – by Scott Buzby

Disclosures: Kuno and Wald report no relevant financial disclosures. Please see the study and editorial for all other authors’ relevant financial disclosures.