Use of direct‐acting oral anticoagulants in solid organ transplantation: A systematic review

Bixby, Alexandra L; Lichvar, Alicia; Salerno, David M.; Park, Jeong Mi

doi:10.1002/phar.2485

Cited by 17 publications

(27 citation statements)

References 88 publications

(171 reference statements)

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“…A systematic review undertaken by Bixby et al. found that DOACs had similar efficacy to warfarin with potentially lower bleeding risks across a range of solid organ transplants 24 . The combined findings from these studies provide some reassuring data that DOACs are safe and effective in this population.…”

Section: Discussionmentioning

confidence: 99%

Can direct oral anticoagulants be used in kidney transplant recipients?

Parker

Chu

Morton

et al. 2021

Clinical Transplantation

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Background : Kidney transplant recipients(KTRs) are at an increased risk of venous thromboembolism (VTE) and atrial fibrillation(AF). Direct oral anticoagulants (DOACs) have shown important advantages over vitamin K antagonists; however, in KTRs, concerns regarding interactions and use in severe kidney disease may limit their use. This evaluation describes a large UK kidney transplant center's experience of DOACs in KTRs with CrCl > 15 mL/min. Methods Electronic records were reviewed for all adult KTRs at Manchester University Foundation Trust Hospitals taking DOACs between January 2018 and October 2020 with VTE or AF. The primary outcome was trough and peak DOAC levels within the expected reference ranges and secondary outcomes included bleeding and thrombotic events. Results In 31 KTRs taking DOACS, eight patients had a CrCl < 30 mL/min. Overall, 94% (62/66) of DOAC levels were within the recommended ranges. There were no thrombotic events and four bleeding events (two major and two clinically relevant non‐major bleeds). The overall bleeding rate was 6.9 per 100 patient‐years at risk. Conclusions There was no evidence of a significant interaction of apixaban or rivaroxaban with CNIs based on expected DOAC and CNI levels. Their use was found to be safe and effective with no VTE events and bleeding episodes similar to published trial data.

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Section: Discussionmentioning

confidence: 99%

Can direct oral anticoagulants be used in kidney transplant recipients?

Parker

Chu

Morton

et al. 2021

Clinical Transplantation

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“…The slow adoption of DOACs by the transplant community is likely due to limited body of literature with small sample sizes evaluating the use of DOACs in this population. 13,14 A systematic review of the use of DOACs only identified 9 full-text studies evaluating the safety and/or efficacy of DOACs in solid organ transplant recipients. The largest of these studies included 99 recipients while the others included 52 recipients or less.…”

Section: Introductionmentioning

confidence: 99%

“…The largest of these studies included 99 recipients while the others included 52 recipients or less. 14 Lichvar and colleagues conducted a nationwide survey of adult transplant programs in the United States to assess DOAC utilization. While 94.3% of survey responders allowed DOAC therapy in the posttransplant setting, 73.8% did not preemptively adjust the DOAC dose for recipients receiving tacrolimus (TAC), which demonstrates practice discordance across sites.…”

Section: Introductionmentioning

confidence: 99%

The Impact of Rivaroxaban and Apixaban on Tacrolimus Trough Levels

et al. 2021

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The solid organ transplant community is slow to adopt the routine practice of using direct oral anticoagulants. Rivaroxaban and apixaban share common metabolic pathways with tacrolimus. This study aimed to clarify the impact of rivaroxaban/apixaban on tacrolimus troughs. Fifty solid organ transplant recipients with concomitant use of tacrolimus and rivaroxaban/apixaban were retrospectively assessed for changes in tacrolimus troughs and dose. Average dose-adjusted tacrolimus troughs and average tacrolimus total daily doses prior to and after rivaroxaban/apixaban initiation were compared. Subgroup analyses evaluating rivaroxaban and apixaban individually were performed. Rivaroxaban was prescribed to 18 recipients, and apixaban was prescribed to 32 recipients. Transplanted organs included kidney (n = 22), lung (n = 18), liver (n = 7), simultaneous pancreas and kidney (n = 1), and simultaneous kidney and liver (n = 2). The median doseadjusted tacrolimus trough and tacrolimus total daily dose prior to rivaroxaban/apixaban initiation was 2.15 ng/mL/mg (IQR 1.17, 3.37) and 4 mg (IQR 1.88, 6.25), respectively. The median dose-adjusted tacrolimus trough and tacrolimus total daily dose after rivaroxaban/apixaban initiation was 2.16 ng/mL/mg (IQR 1.24, 4.10) and 3.55 mg (IQR 1.5, 6.35), respectively. No significant difference was found between average dose-adjusted tacrolimus troughs or tacrolimus total daily doses before and after rivaroxaban/apixaban initiation or in the individual subgroup analyses for rivaroxaban/apixaban. It is unlikely that initiating rivaroxaban/apixaban affects tacrolimus troughs or requires tacrolimus dose adjustment. This study does not elucidate if tacrolimus affects rivaroxaban/apixaban pharmacokinetics or pharmacodynamics.

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“…In addition, apixaban (∼27%) and rivaroxaban (∼33%) are cleared by kidneys. 7 Theoretically, chronic calcineurin mediated renal insufficiency can potentially increase the risk of bleeding. However, recent data indicates that DOACs are comparable to warfarin in SOT recipients.…”

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confidence: 99%

Safety of direct oral anticoagulants in solid organ transplant recipients: A meta‐analysis

Zakko

Ganapathi

Whitson

et al. 2021

Clinical Transplantation

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There is limited evidence comparing direct oral anticoagulants (DOACs) and warfarin in solid organ transplant (SOT) recipients. We performed a pooled analysis to study the safety and efficacy of DOACs in this patient population. We searched PubMed, Embase, and Scopus databases using the search terms "heart transplant" or "lung transplant" or "liver transplant" or "kidney transplant" or "pancreas transplant" and "direct oral anticoagulant" for literature search. Random effects model with Mantel-Haenszel method was used to pool the outcomes. Pooled analysis included 489 patients, of which 259 patients received DOACs and 230 patients received warfarin. When compared to warfarin, the use of DOACs was associated with decreased risk of composite bleed (RR .49, 95% CI .32-.76, p = .002). There were no differences in rates of major bleeding (RR .55, 95% CI .20-1.49, p = .24) or venous thromboembolism (RR .65, 95% CI .25-1.70, p = .38) between the two groups. Evidence from pooled analysis suggests that DOACs are comparable to warfarin in terms of safety in SOT recipients. Further research is warranted to conclusively determine whether DOACs are safe alternatives to warfarin for anticoagulation in SOT recipients. K E Y W O R D Scoagulation and hemostasis, meta-analysis, pharmacokinetics/pharmacodynamics INTRODUCTIONSolid organ transplant (SOT) recipients are at significant risk for requiring long-term post-operative anticoagulation. Studies demonstrate up to a 15% incidence of pulmonary embolism, 45% incidence of venous thromboembolism (VTE), and 25% incidence of atrial fibrillation or flutter following lung transplantation. [1][2][3] Heart transplantation is associated with 8.5% and a 13% incidence of VTE and atrial fibrillation, respectively. 4 As such, a significant percentage of this patient population requires systemic anticoagulation. The vitamin K antago-

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Use of direct‐acting oral anticoagulants in solid organ transplantation: A systematic review

Cited by 17 publications

References 88 publications

Can direct oral anticoagulants be used in kidney transplant recipients?

Can direct oral anticoagulants be used in kidney transplant recipients?

The Impact of Rivaroxaban and Apixaban on Tacrolimus Trough Levels

Safety of direct oral anticoagulants in solid organ transplant recipients: A meta‐analysis

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