Everolimus immunosuppression in de novo heart transplant recipients: What does the evidence tell us now?

Zuckermann, Andreas; Wang, Shoei‐Shen; Epailly, Éric; Barten, Markus J.; Sigurdardottir, Vilborg; Segovia, Javier; Varnous, Shaïda; Turazza, F.; Potena, Luciano; Lehmkuhl, H.

doi:10.1016/j.trre.2013.03.002

Cited by 30 publications

(18 citation statements)

References 80 publications

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“…In accordance with the present publications, main reasons for mTOR introduction in our study population were avoidance of further deterioration of renal function, rejection profile, development of posttransplant CAV, and malignancies 11. However, combination of mTORs with CNIs may also be indicated in patients intolerant to MMF, allowing CNI reduction and minimization of consecutive possible dose-dependent adverse drug effects of CNIs, like nephrotoxicity and tremor 11,15,31. In the present study, a large percentage of patients were switched to CNI/mTOR because of adverse drug effects of previous immunosuppressive regimens.…”

Section: Discussionsupporting

confidence: 83%

“…Due to its antiproliferative effects,12,28–30 mTOR-based immunosuppression is an attractive option in patients with CAV,16 posttransplant malignancies,11,14,15,19 or in patients with impaired renal function 11,19. In accordance with the present publications, main reasons for mTOR introduction in our study population were avoidance of further deterioration of renal function, rejection profile, development of posttransplant CAV, and malignancies 11.…”

Section: Discussionsupporting

confidence: 81%

“…Due to its antiproliferative effects, mTOR-based immunosuppression appears to be favorable regarding development and progression of cardiac allograft vasculopathy (CAV) 11–14. Moreover, posttransplant malignancy and CNI minimization,11,14,15 for example, to avoid further deterioration of renal function, are important reasons for mTOR-based immunosuppression.…”

Section: Introductionmentioning

confidence: 99%

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Renal function in heart transplant patients after switch to combined mammalian target of rapamycin inhibitor and calcineurin inhibitor therapy

Helmschrott¹,

Rivinius²,

Brückner³

et al. 2017

DDDT

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BackgroundA calcineurin inhibitor (CNI)-based immunosuppression combined with mammalian target of rapamycin inhibitors (mTORs) seems to be attractive in patients after heart transplantation (HTX) in special clinical situations, for example, in patients with adverse drug effects of prior immunosuppression. Previous studies in patients after HTX detected advantageous effects regarding renal function of a tacrolimus (TAC)-based vs cyclosporine-A (CSA)-based immunosuppression (in combination with mycophenolate mofetil). However, data regarding renal function after HTX in mTOR/CNI patients remain limited.AimPrimary end point of the present study was to analyze renal function in HTX patients 1 year after switch to an mTOR/CNI-based immunosuppression.MethodsData of 80 HTX patients after change to mTOR/CNI-based immunosuppression were retrospectively analyzed. Renal function was assessed by measured serum creatinine and by estimated glomerular filtration rate (eGFR) calculated from Modification of Diet in Renal Disease equation.ResultsTwenty-nine patients received mTOR/CSA-based treatment and 51 patients received mTOR/TAC-based therapy. At time of switch and at 1-year follow-up, serum creatinine and eGFR did not differ significantly between both study groups (all P=not statistically significant). Analysis of variances with repeated measurements detected a similar change of renal function in both study groups.ConclusionThe present study detected no significant differences between both mTOR/CNI study groups, indicating a steady state of renal function in HTX patients after switch of immunosuppressive regimen.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

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Renal function in heart transplant patients after switch to combined mammalian target of rapamycin inhibitor and calcineurin inhibitor therapy

Helmschrott¹,

Rivinius²,

Brückner³

et al. 2017

DDDT

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“…In the SCHEDULE (Scandinavian heart transplant everolimus de novo study with early calcineurin inhibitors avoidance) trial, patients were randomized to everolimus with reduced CNI followed by CNI withdrawal at week [7][8][9][10][11] or to a conventional CNI-based regimen. At the end of the 12-month trial, the everolimus-treated patient cohort had significantly better renal function than the control group and significantly lower incidence of CAV, but mild to moderate acute rejection was more frequent after CNI therapy was withdrawn (11).…”

Section: Introductionmentioning

confidence: 99%

Everolimus Initiation With Early Calcineurin Inhibitor Withdrawal in De Novo Heart Transplant Recipients: Three-Year Results From the Randomized SCHEDULE Study

Andreassen

Andersson

Gustafsson

et al. 2016

American Journal of Transplantation

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In a randomized, open‐label trial, de novo heart transplant recipients were randomized to everolimus (3–6 ng/mL) with reduced‐exposure calcineurin inhibitor (CNI; cyclosporine) to weeks 7–11 after transplant, followed by increased everolimus exposure (target 6–10 ng/mL) with cyclosporine withdrawal or standard‐exposure cyclosporine. All patients received mycophenolate mofetil and corticosteroids. A total of 110 of 115 patients completed the 12‐month study, and 102 attended a follow‐up visit at month 36. Mean measured GFR (mGFR) at month 36 was 77.4 mL/min (standard deviation [SD] 20.2 mL/min) versus 59.2 mL/min (SD 17.4 mL/min) in the everolimus and CNI groups, respectively, a difference of 18.3 mL/min (95% CI 11.1–25.6 mL/min; p < 0.001) in the intention to treat population. Multivariate analysis showed treatment to be an independent determinant of mGFR at month 36. Coronary intravascular ultrasound at 36 months revealed significantly reduced progression of allograft vasculopathy in the everolimus group compared with the CNI group. Biopsy‐proven acute rejection grade ≥2R occurred in 10.2% and 5.9% of everolimus‐ and CNI‐treated patients, respectively, during months 12–36. Serious adverse events occurred in 37.3% and 19.6% of everolimus‐ and CNI‐treated patients, respectively (p = 0.078). These results suggest that early CNI withdrawal after heart transplantation supported by everolimus, mycophenolic acid and steroids with lymphocyte‐depleting induction is safe at intermediate follow‐up. This regimen, used selectively, may offer adequate immunosuppressive potency with a sustained renal advantage.

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“…A series of randomized trials has examined the use of everolimus therapy following heart transplantation, 1 and that, potentially, the risk of post-transplant malignancy could be lowered. [2][3][4] While various everolimus protocols have been evaluated, including de novo use with or without CNI therapy and conversion of maintenance patients to CNI-free or reduced-CNI regimens, the optimal mode for its use is not yet established.…”

Section: Introductionmentioning

confidence: 99%

The MANDELA study: A multicenter, randomized, open-label, parallel group trial to refine the use of everolimus after heart transplantation

Deuse¹,

Bara

Barten³

et al. 2015

Contemporary Clinical Trials

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Everolimus immunosuppression in de novo heart transplant recipients: What does the evidence tell us now?

Cited by 30 publications

References 80 publications

Renal function in heart transplant patients after switch to combined mammalian target of rapamycin inhibitor and calcineurin inhibitor therapy

Renal function in heart transplant patients after switch to combined mammalian target of rapamycin inhibitor and calcineurin inhibitor therapy

Everolimus Initiation With Early Calcineurin Inhibitor Withdrawal in De Novo Heart Transplant Recipients: Three-Year Results From the Randomized SCHEDULE Study

The MANDELA study: A multicenter, randomized, open-label, parallel group trial to refine the use of everolimus after heart transplantation

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