Efficacy and safety of direct oral anticoagulants in solid organ transplant recipients: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

GAO Si ¹ , PAN Mangmang ² , GU Zhichun ² ,  GUO Sitong ¹

1. Department of Pharmacy, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, P. R. China;
2. Department of Pharmacy, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P. R. China;

Corresponding author：

GUO Sitong, Email: 347585774@qq.com

Keywords：

Direct oral anticoagulant; Vitamin K antagonists; Solid organ transplant; Meta-analysis; Systematic review

DOI：

10.7507/1672-2531.202408043

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Objective To systematically evaluate the efficacy and safety of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKA) in solid organ transplant (SOT) recipients. Methods The PubMed, Embase, Web of Science, Cochrane Library, CNKI, WanFang Data, CBM and VIP databases were electronically searched to collect clinical studies on DOACs (rivaroxaban, apixaban, idoxaban, dabigatran) compared with VKA in SOT recipients from inception to May 15, 2024. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using RevMan 5.3 software. Results A total of 11 cohort studies involving 1 236 SOT recipients were included. The meta-analysis results showed that compared with VKA, DOACs could reduce the risk of any bleeding (RR=0.47, 95%CI 0.37 to 0.60, P<0.05) and major bleeding (RR=0.56, 95%CI 0.37 to 0.84, P<0.05) in SOT recipients. But there were no statistically significant differences in the total incidence of thrombotic events, VTE incidence, and stroke incidence between the two groups. Conclusion Current evidence shows that DOACs are not inferior to VKA in anticoagulation therapy for SOT recipients, but they perform better in terms of any bleeding and major bleeding. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.

1.	Tsai HI, Liu FC, Lee CW, et al. Cardiovascular disease risk in patients receiving organ transplantation: a national cohort study. Transpl Int, 2017, 30(11): 1161-1171.
2.	Sáez-Giménez B, Berastegui C, Loor K, et al. Deep vein thrombosis and pulmonary embolism after solid organ transplantation: an unresolved problem. Transplant Rev (Orlando), 2015, 29(2): 85-92.
3.	Lentine KL, Schnitzler MA, Abbott KC, et al. Incidence, predictors, and associated outcomes of atrial fibrillation after kidney transplantation. Clin J Am Soc Nephrol, 2006, 1(2): 288-296.
4.	La Manna G, Boriani G, Capelli I, et al. Incidence and predictors of postoperative atrial fibrillation in kidney transplant recipients. Transplantation, 2013, 96(11): 981-986.
5.	Salerno DM, Tsapepas D, Papachristos A, et al. Direct oral anticoagulant considerations in solid organ transplantation: a review. Clin Transplant, 2017, 31(1): 10.1111/ctr. 12873.
6.	Steffel J, Collins R, Antz M, et al. 2021 European heart rhythm association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Europace, 2021, 23(10): 1612-1676.
7.	中华医学会心血管病学分会, 中国生物医学工程学会心律分会. 心房颤动诊断和治疗中国指南. 中华心血管病杂志, 2023, 51(6): 572-618.
8.	Stevens SM, Woller SC, Kreuziger LB, et al. Antithrombotic therapy for VTE disease: second update of the CHEST guideline and expert panel report. Chest, 2021, 160(6): 545-608.
9.	Zakko J, Ganapathi AM, Whitson BA, et al. Safety of direct oral anticoagulants in solid organ transplant recipients: A meta-analysis. Clin Transplant, 2022, 36(3): e14513.
10.	He C, Yao C. Direct oral anticoagulants vs Vitamin-K antagonists in solid organ transplant recipients: a systematic review and meta-analysis. Pak J Med Sci, 2024, 40(6): 1267-1273.
11.	Shitanishi L, Fan A, Khuu T, et al. Direct oral anticoagulants versus warfarin in adult heart transplant recipients. JHLT Open, 2024, 4: 100061.
12.	Santoro F, Casanova A, Simone S, et al. Immunosuppressive therapy and oral anticoagulation in kidney transplant recipients: direct oral anticoagulants versus vitamin-k antagonists. Eur J Intern Med, 2024, 119: 71-77.
13.	Firth C, Shamoun F, Apolinario M, et al. Safety and mortality outcomes for direct oral anticoagulants in renal transplant recipients. PLoS One, 2023, 18(5): e0285412.
14.	Darche FF, Fabricius LC, Helmschrott M, et al. Oral anticoagulants after heart transplantation-comparison between vitamin K antagonists and direct oral anticoagulants. J Clin Med, 2023, 12(13): 4334.
15.	Zaitoun MF, Sheikh ME, Faifi ASA, et al. The use of non-vitamin k antagonist oral anticoagulants in post-kidney transplantation, single-center experience. Transplant Proc, 2021, 53(10): 2918-2922.
16.	Pfrepper C, Herber A, Weimann A, et al. Safety and efficacy of direct oral anticoagulants under long-term immunosuppressive therapy after liver, kidney and pancreas transplantation. Transpl Int, 2021, 34(3): 423-435.
17.	Santeusanio AD, Weinberg AD, Florman SS, et al. Safety of direct-acting oral anticoagulants relative to warfarin in a matched cohort of liver transplant recipients. Clin Transplant, 2020, 34(1): e13756.
18.	Leon J, Sabbah L, Aubert O, et al. Efficacy and safety of direct oral anticoagulants in kidney transplantation: a single-center pilot experience. Transplantation, 2020, 104(12): 2625-2631.
19.	Henricksen EJ, Tremblay-Gravel M, Moayedi Y, et al. Use of direct oral anticoagulants after heart transplantation. J Heart Lung Transplant, 2020, 39(4): 399-401.
20.	Bixby AL, Shaikh SA, Naik AS, et al. Safety and efficacy of direct-acting oral anticoagulants versus warfarin in kidney transplant recipients: a retrospective single-center cohort study. Transpl Int, 2020, 33(7): 740-751.
21.	Hazelcorn J, Yau R, Sabagha N, et al. Risk of major bleeding in solid organ transplant recipients taking calcineurin inhibitors concomitantly with direct oral anticoagulants compared to warfarin. Am J Transplant, 2017, 17(2): 640.
22.	Fahmy O, Fahmy UA, Alhakamy NA, et al. Single-port versus multiple-port robot-assisted radical prostatectomy: a systematic review and meta-analysis. J Clin Med, 2021, 10(24): 5723.
23.	Lam E, Bashir B, Chaballa M, et al. Drug interactions between direct-acting oral anticoagulants and calcineurin inhibitors during solid organ transplantation: considerations for therapy. Expert Rev Clin Pharmacol, 2019, 12(8): 781-790.
24.	Al Aly Z, Abbas S, Moore E, et al. The natural history of renal function following orthotopic heart transplant. Clin Transplant, 2005, 19(5): 683-689.
25.	Burra P, Senzolo M, Masier A, et al. Factors influencing renal function after liver transplantation. Results from the MOST, an international observational study. Dig Liver Dis, 2009, 41(5): 350-356.

1. Tsai HI, Liu FC, Lee CW, et al. Cardiovascular disease risk in patients receiving organ transplantation: a national cohort study. Transpl Int, 2017, 30(11): 1161-1171.
2. Sáez-Giménez B, Berastegui C, Loor K, et al. Deep vein thrombosis and pulmonary embolism after solid organ transplantation: an unresolved problem. Transplant Rev (Orlando), 2015, 29(2): 85-92.
3. Lentine KL, Schnitzler MA, Abbott KC, et al. Incidence, predictors, and associated outcomes of atrial fibrillation after kidney transplantation. Clin J Am Soc Nephrol, 2006, 1(2): 288-296.
4. La Manna G, Boriani G, Capelli I, et al. Incidence and predictors of postoperative atrial fibrillation in kidney transplant recipients. Transplantation, 2013, 96(11): 981-986.
5. Salerno DM, Tsapepas D, Papachristos A, et al. Direct oral anticoagulant considerations in solid organ transplantation: a review. Clin Transplant, 2017, 31(1): 10.1111/ctr. 12873.
6. Steffel J, Collins R, Antz M, et al. 2021 European heart rhythm association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Europace, 2021, 23(10): 1612-1676.
7. 中华医学会心血管病学分会, 中国生物医学工程学会心律分会. 心房颤动诊断和治疗中国指南. 中华心血管病杂志, 2023, 51(6): 572-618.
8. Stevens SM, Woller SC, Kreuziger LB, et al. Antithrombotic therapy for VTE disease: second update of the CHEST guideline and expert panel report. Chest, 2021, 160(6): 545-608.
9. Zakko J, Ganapathi AM, Whitson BA, et al. Safety of direct oral anticoagulants in solid organ transplant recipients: A meta-analysis. Clin Transplant, 2022, 36(3): e14513.
10. He C, Yao C. Direct oral anticoagulants vs Vitamin-K antagonists in solid organ transplant recipients: a systematic review and meta-analysis. Pak J Med Sci, 2024, 40(6): 1267-1273.
11. Shitanishi L, Fan A, Khuu T, et al. Direct oral anticoagulants versus warfarin in adult heart transplant recipients. JHLT Open, 2024, 4: 100061.
12. Santoro F, Casanova A, Simone S, et al. Immunosuppressive therapy and oral anticoagulation in kidney transplant recipients: direct oral anticoagulants versus vitamin-k antagonists. Eur J Intern Med, 2024, 119: 71-77.
13. Firth C, Shamoun F, Apolinario M, et al. Safety and mortality outcomes for direct oral anticoagulants in renal transplant recipients. PLoS One, 2023, 18(5): e0285412.
14. Darche FF, Fabricius LC, Helmschrott M, et al. Oral anticoagulants after heart transplantation-comparison between vitamin K antagonists and direct oral anticoagulants. J Clin Med, 2023, 12(13): 4334.
15. Zaitoun MF, Sheikh ME, Faifi ASA, et al. The use of non-vitamin k antagonist oral anticoagulants in post-kidney transplantation, single-center experience. Transplant Proc, 2021, 53(10): 2918-2922.
16. Pfrepper C, Herber A, Weimann A, et al. Safety and efficacy of direct oral anticoagulants under long-term immunosuppressive therapy after liver, kidney and pancreas transplantation. Transpl Int, 2021, 34(3): 423-435.
17. Santeusanio AD, Weinberg AD, Florman SS, et al. Safety of direct-acting oral anticoagulants relative to warfarin in a matched cohort of liver transplant recipients. Clin Transplant, 2020, 34(1): e13756.
18. Leon J, Sabbah L, Aubert O, et al. Efficacy and safety of direct oral anticoagulants in kidney transplantation: a single-center pilot experience. Transplantation, 2020, 104(12): 2625-2631.
19. Henricksen EJ, Tremblay-Gravel M, Moayedi Y, et al. Use of direct oral anticoagulants after heart transplantation. J Heart Lung Transplant, 2020, 39(4): 399-401.
20. Bixby AL, Shaikh SA, Naik AS, et al. Safety and efficacy of direct-acting oral anticoagulants versus warfarin in kidney transplant recipients: a retrospective single-center cohort study. Transpl Int, 2020, 33(7): 740-751.
21. Hazelcorn J, Yau R, Sabagha N, et al. Risk of major bleeding in solid organ transplant recipients taking calcineurin inhibitors concomitantly with direct oral anticoagulants compared to warfarin. Am J Transplant, 2017, 17(2): 640.
22. Fahmy O, Fahmy UA, Alhakamy NA, et al. Single-port versus multiple-port robot-assisted radical prostatectomy: a systematic review and meta-analysis. J Clin Med, 2021, 10(24): 5723.
23. Lam E, Bashir B, Chaballa M, et al. Drug interactions between direct-acting oral anticoagulants and calcineurin inhibitors during solid organ transplantation: considerations for therapy. Expert Rev Clin Pharmacol, 2019, 12(8): 781-790.
24. Al Aly Z, Abbas S, Moore E, et al. The natural history of renal function following orthotopic heart transplant. Clin Transplant, 2005, 19(5): 683-689.
25. Burra P, Senzolo M, Masier A, et al. Factors influencing renal function after liver transplantation. Results from the MOST, an international observational study. Dig Liver Dis, 2009, 41(5): 350-356.

Chinese Journal of Evidence-Based Medicine

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