Quadritherapy vs standard tritherapy immunosuppressant regimen after heart transplantation: A propensity score-matched cohort analysis.
clinical research/practice
heart (allograft) function/dysfunction
heart transplantation/cardiology
immunosuppressant-mechanistic target of rapamycin: everolimus
immunosuppression/immune modulation
immunosuppressive regimens-maintenance
rejection: acute
Journal
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
ISSN: 1600-6143
Titre abrégé: Am J Transplant
Pays: United States
ID NLM: 100968638
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
15
12
2019
revised:
20
02
2020
accepted:
09
03
2020
pubmed:
18
3
2020
medline:
22
6
2021
entrez:
18
3
2020
Statut:
ppublish
Résumé
After heart transplant, adding everolimus (EVL) to standard immunosuppressive regimen mostly relies on converting calcineurin inhibitors (CNIs) into EVL. The aim of this study was to describe the effects of combining low-dose EVL and CNIs in maintenance immunosuppression regimen (quadritherapy) and compare it with standard tritherapy associating standard-dose CNIs, mycophenolate mofetil, and corticosteroids. In the 3-year registry cohort of heart transplanted patients, those who received quadritherapy were compared with those who received tritherapy. EVL was added after 3 months posttransplant. Three analyses were performed to control for confounders: propensity score matching, multivariable survival, and inverse probability score weighting analyses. Among 213 patients who were included (75 with quadritherapy), propensity score matching selected 64 unique pairs of patients with similar characteristics. In the matched cohort (n = 128), quadritherapy was associated with fewer deaths (3 [4.7%] vs 17 [21.9%], P = .007) and biopsy-proven acute rejections (15 [23.4%] vs 31 [48.4%], P = .002). These results were confirmed in the overall cohort (n = 213), after multivariable and inverse probability score weighting analyses. Renal function and donor-specific HLA-antibodies remained similar in both groups. Low-dose combination quadritherapy was associated with fewer deaths and rejections, compared with standard immunosuppression tritherapy.
Identifiants
pubmed: 32180354
doi: 10.1111/ajt.15849
pii: S1600-6135(22)22467-8
doi:
Substances chimiques
Immunosuppressive Agents
0
Mycophenolic Acid
HU9DX48N0T
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2791-2801Informations de copyright
© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.
Références
Andreassen AK, Andersson B, Gustafsson F, et al. Everolimus initiation with early calcineurin inhibitor withdrawal in de novo heart transplant recipients: three-year results from the randomized SCHEDULE study. Am J Transplant. 2016;16(4):1238-1247.
Asleh R, Briasoulis A, Kremers WK, et al. Long-term sirolimus for primary immunosuppression in heart transplant recipients. J Am Coll Cardiol. 2018;71(6):636-650.
Andreassen AK, Andersson B, Gustafsson F, et al. Everolimus initiation and early calcineurin inhibitor withdrawal in heart transplant recipients: a randomized trial. Am J Transplant. 2014;14(8):1828-1838.
Keogh A, Richardson M, Ruygrok P, et al. Sirolimus in de novo heart transplant recipients reduces acute rejection and prevents coronary artery disease at 2 years: a randomized clinical trial. Circulation. 2004;110(17):2694-2700.
Nguyen LS, Vautier M, Allenbach Y, et al. Sirolimus and mTOR inhibitors: a review of side effects and specific management in solid organ transplantation. Drug Saf. 2019;42(7):813-825.
Ross H, Pflugfelder P, Haddad H, et al. Reduction of cyclosporine following the introduction of everolimus in maintenance heart transplant recipients: a pilot study. Transpl Int. 2010;23(1):31-37.
Zuckermann A, Wang SS, Ross H, et al. Efficacy and safety of low-dose cyclosporine with everolimus and steroids in de novo heart transplant patients: a multicentre, randomized trial. J Transplant. 2011;2011:535983.
Gullestad L, Iversen M, Mortensen S-A, et al. Everolimus with reduced calcineurin inhibitor in thoracic transplant recipients with renal dysfunction: a multicenter, randomized trial. Transplantation. 2010;89(7):864-872.
Gullestad L, Eiskjaer H, Gustafsson F, et al. Long-term outcomes of thoracic transplant recipients following conversion to everolimus with reduced calcineurin inhibitor in a multicenter, open-label, randomized trial. Transplant Int. 2016;29(7):819-829.
Gustafsson F, Andreassen AK, Andersson B, et al. Everolimus initiation with early calcineurin inhibitor withdrawal in de novo heart transplant recipients: long-term follow-up from the randomized SCHEDULE study. Transplantation. 2020;104(1):154-164.
Colvin MM, Cook JL, Chang PP, et al. Sensitization in heart transplantation: emerging knowledge: a scientific statement from the American Heart Association. Circulation. 2019;139(12):e553-e578.
Nguyen LS, Coutance G, Salem J-E, et al. Effect of recipient gender and donor-specific antibodies on antibody-mediated rejection after heart transplantation. Am J Transplant. 2019;19(4):1160-1167.
Berry GJ, Burke MM, Andersen C, et al. The 2013 International Society for Heart and Lung Transplantation working formulation for the standardization of nomenclature in the pathologic diagnosis of antibody-mediated rejection in heart transplantation. J Heart Lung Transplant. 2013;32(12):1147-1162.
Kobashigawa J, Crespo-Leiro MG, Ensminger SM, et al. Report from a consensus conference on antibody-mediated rejection in heart transplantation. J Heart Lung Transplant. 2011;30(3):252-269.
Stewart S, Winters GL, Fishbein MC, et al. Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection. J Heart Lung Transplant. 2005;24(11):1710-1720.
Mehra MR, Crespo-Leiro MG, Dipchand A, et al. International Society for Heart and Lung Transplantation working formulation of a standardized nomenclature for cardiac allograft vasculopathy-2010. J Heart Lung Transplant. 2010;29(7):717-727.
Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease study group. Ann Intern Med. 1999;130(6):461-470.
Austin PC, Stuart EA. The performance of inverse probability of treatment weighting and full matching on the propensity score in the presence of model misspecification when estimating the effect of treatment on survival outcomes. Stat Methods Med Res. 2017;26(4):1654-1670.
Eisen HJ, Tuzcu EM, Dorent R, et al. Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients. N Engl J Med. 2003;349(9):847-858.
Barten MJ, Hirt SW, Garbade J, et al. Comparing everolimus-based immunosuppression with reduction or withdrawal of calcineurin inhibitor reduction from 6 months after heart transplantation: the randomized MANDELA study. Am J Transplant. 2019;19(11):3006-3017.
Gullestad L, Mortensen S-A, Eiskjaer H, et al. Two-year outcomes in thoracic transplant recipients after conversion to everolimus with reduced calcineurin inhibitor within a multicenter, open-label, randomized trial. Transplantation. 2010;90(12):1581-1589.
O'Leary JG, Samaniego M, Crespo Barrio M, et al. The influence of immunosuppressive agents on the risk of de novo donor-specific HLA antibody production in solid organ transplant recipients. Transplantation. 2016;100(1):39-53.
Baran DA, Zucker MJ, Arroyo LH, et al. A prospective, randomized trial of single-drug versus dual-drug immunosuppression in heart transplantation: the tacrolimus in combination, tacrolimus alone compared (TICTAC) trial. Circ Heart Fail. 2011;4(2):129-137.
Gude E, Gullestad L, Andreassen AK. Everolimus immunosuppression for renal protection, reduction of allograft vasculopathy and prevention of allograft rejection in de-novo heart transplant recipients: could we have it all? Curr Opin Organ Transplant. 2017;22(3):198-206.
Jennings DL, Lange N, Shullo M, et al. Outcomes associated with mammalian target of rapamycin (mTOR) inhibitors in heart transplant recipients: a meta-analysis. Int J Cardiol. 2018;265:71-76.
Uchida J, Iwai T, Nakatani T. Introduction of everolimus in kidney transplant recipients at a late posttransplant stage. World J Transplant. 2018;8(5):150-155.