TOR inhibitors following heart transplant

Czech version

Authors: L. Špinarová
Published in: Kardiol Rev Int Med 2011, 13(1): 44-47
Category: From Heart Failure to Heart Transplantation

Overview

This is an overview of the use of new immunosuppressive medication – TOR inhibitors – including everolimus and sirolimus on patients following heart transplants. It is possible to administer these medicaments de novo or to switch from existing therapy. Indicators for a switch are calcineurin nephropathy, vasculopathies, malignities, myopathies and neurotoxicity. These medicaments thus increase the options for immunosuppression, with treatment administered according to any accompanying illnesses suffered by patients.

Keywords:
transplants – TOR inhibitors – immunosuppression

Sources

1. Kurian KC, Addisu A. Sirolimus: A novel immunosupressive drug in heart transplantation. Rec Patents on Cardiovasc Drug Discovery 2009; 4: 187–191.

2. Radovancevic B, El-Sabrout R, Thomas C et al. Rapamycin reduces rejection in heart transplant recipients. Transplantation Proceedings 2001; 33: 3221–3222.

3. Rothenburger M, Zuckermann A, Bara C et al. Certican Consensus Study Group. Recommendations for the use of everolimus (Certican) in heart transplantation: results from the second German-Austrian Certican Consensus Conference. J Heart Lung Transplant 2007; 26: 305–311.

4. Meiser B, Kaczmarek I, Muller M et al. Low-dose tacrolimus/sirolimus and steroid withdrawal in heart recipients is highly efficacious. J Heart Lung Transplantat 2007; 26: 598–603.

5. Mueller M, Meiser B, Groetzner J et al. Sirolimus in combination with tacrolimus for primary immunosuppression after heart transplantation. J Heart Lung Transplant 2004; 23: S46.

6. Radovancevic B, Thomas CD, Ford EL et al. Comparison of rapamycin and mycophenolate mofetil therapy in heart transplant recipients treated with tacrolimus. Heart transplantation Abstracts: 527.

7. Keogh A, Richardson M, Ruygok P et al. Sirolimus in de novo heart transplant recipients reduces acute rejection and prevents coronary artery disease at 2 years. Circulation 2004; 110: 2694–2700.

8. Kobashigawa JA, Muller LW, Russell SD et al. Study Investigators. Tacrolimus with mycophenolate mofetil (MMF) or sirolimus vs cyclosporine with MMF in cardiac transplant patients: 1-year report. Am J Transplant 2006; 6: 1377–1386.

9. Eisen H, Kobashigawa H, Starling RC et al. 24-month safety results of a randomized, multicenter, double-blind study of everolimus vs azathioprine in de novo heart transplant recepients. J Heart Lung Transpl 2004; 23 (Suppl. 2): S45.

10. Haverich A, Tuzcu EM, Vigano M et al. Everolimus in de novo cardiac transplant recipients. 24-month follow-up. J Heart Lung Transpl 2003; 22 (Suppl. 1): S140–S141.

11. Tuzcu EM, Kobashigawa JA, Eisen HJ et al. Favorable effect of everolimus on cardiac allograft vasculopathy is maintaned through 24 months. J Heart Lung Transpl 2004; 23 (Suppl 2): S51.

12. Snell GI, Levvey BJ, Chin W et al. Rescue therapy: A role for sirolimus in lung and heart transplant recipients. Transpl Proc 2001; 33: 1084–1085.

13. Špinarová L. Transplantace srdce. Cor et Vasa 2008: 50: 133–138.

14. Málek I. Transplantace srdce. Postgrad Med 1999; 1: 95–100.

15. Delgado JF, Crespo MG, Manito N et al. Usefulness of sirolimus as rescue therapy in heart transplant recipients with renal failure: Analysis of the Spanish multicenter observational study (RAPACOR). Transplant Proc 2009; 41: 3835–3837.

16. Potena L, Bianchi IG, Magnani G et al. Cyclosporine lowering with everolimus or mycophenolate to preserve renal function in heart recipients: a randomised study. Transplantation 2010; 89: 263–265.

17. Snell GI, Levvey BJ, Chin W et al. Sirolimus allows renal recovery in lung and heart transplant recipients with chronic renal impairment. J Heart Lung Transplant 2002; 21: 540–546.

18. Groetzner J, Kaczmarek I, Muller M et al. Calcineurin-inhibitor-free immunosuppression with mycophenolatmofetil and sirolimus after cardiac transplantation is safe and improves renal function significantly: 1 year follow up. Transplantation 2004; 78 (Suppl. 1): S161.

19. Lehneman JB, Smallwood GA, Corby DÁ et al. Retrospective review of sirolimus use for chronic rejection and renal dysfunction in heart transplant recipients. Am J Transpl 2004; 4 (Suppl. 8): S177.

20. Hunt J, Lerman M, Dewey T et al. Conversion to sirolimus lessens renal dysfunction in heart transplant patients. J Heart Lung Transpl 2004; 23 (2S): 113.

21. Gude E, Gullestad L, Arora S et al. Benefit of early conversion from CNI-based to everolimus based immunosuppression in heart transplantation. J Heart Lung Transplant 2010; 29: 641–647.

22. Delgado JF, Manito N, Segovia J et al. The use of proliferation signal inhibitors in the prevention and treatment of allograft vasculopathy in heart transplantation. Transplant Rev 2009; 23: 69–79.

23. Mancini D, Pinney S, Burkhoff D et al. Use of rapamycin slows progression of cardiac transplantation vasculopathy. Circulation 2003; 108: 48–53.

24. Eisen HJ, Tuzcu EM, Dorent R et al. RAD B253 Study Group. Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients. N Engl J Med 2003; 349: 847–858.

25. Špinarová L, Hude P, Krejčí J et al. Osud pacientů přežívajících deset let po transplantaci srdce se zřetelem k výskytu maligního onemocnění. Cor Vasa 2009; 51: 415–418.

26. Campistol JM, Eris J, Oberbauer R et al. Sirolimus therapy after early cyclosporine withdrawal reduces the risk for cancer in adult renal transplantation. J Am Soc Nephrol 2006; 17: 581–589.

27. Schena FP, Pascoe MD, Alberu J et al. Sirolimus CONVERT Trial Study Group. Conversion from calcineurin inhibitors or sirolimus maintenance therapy in renal allograft recipients: 24-month efficacy and safety results from the CONVERT trial. Transplantation 2009; 87: 233–242.

28. Wasywich CA, Croxson MC, van Doomum GJ et al. Sirolimus for Kaposi’s sarcoma. J Heart Lung Transplant 2006; 25: 726–729.