A Case of Successful Treatment of Severe Hyperlipidemia After Heart Transplantation With Inclisiran

The prognosis after heart transplantation continues to improve. Therefore, the prevention of chronic post-transplant sequelae, such as chronic kidney disease, allograft vasculopathy, and malignancies is becoming increasingly important. Everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), is increasingly used for immunosuppression after heart transplantation. However, everolimus may cause a characteristic complex of adverse effects, including dyslipidemia. Currently there are no guidelines for the long-term screening and treatment of dyslipidemia in heart transplant recipients treated with everolimus. This article presents a clinical case of hypercholesterolemia that developed after the start of the everolimus treatment in a heart recipient. The patient was a 39-year-old man who underwent orthotopic heart transplantation for ischemic cardiomyopathy in 2012 (at the age of 27). In 2019, the patient’s immunosuppressive therapy was converted from mycophenolate mofetil to everolimus due to the development of cardiac allograft vasculopathy. The change in the immunosuppressive therapy was associated with increases in total cholesterol and low-density lipoprotein cholesterol, which were not reversed with a combined lipid-lowering therapy (maximum doses of rosuvastatin, ezetimibe, fenofibrate). A decrease in lipid levels was achieved with a blocker of hepatic proprotein convertase subtilisin/kexin type 9 synthesis at the level of microribonucleic acid (inclisiran). This case demonstrates the difficulties in correcting dyslipidemia in patients with cardiac allograft, since the treatment with the immunosuppressant everolimus worsens existing dyslipidemia. However, the combination lipid-lowering therapy, that affects various elements of the pathogenesis (specifically, the combined inhibition of hydroxymethylglutaryl-CoA reductase with a statin, cholesterol absorption from the small intestine with ezetimibe, and PCSK9 messenger RNA with inclisiran), provides an effective control of blood lipids and minimizing the adverse effects of immunosuppressive therapy, such as cardiac allograft vasculopathy.

1. Hirt SW, Bara C, Barten MJ, Deuse T, Doesch AO, Kaczmarek I et al. Everolimus in Heart Transplantation: An Update. Journal of Transplantation. 2013;2013:683964. DOI: 10.1155/2013/683964

2. Lo P, Kearney K, Muir CA, Song N, Eisman JA, Macdonald PS. Severe Hypertriglyceridemia Associated With Everolimus Treatment After Heart Transplantation. AACE Clinical Case Reports. 2020;6(5):e269–72. DOI: 10.4158/ACCR-2020-0191

3. Som R, Morris PJ, Knight SR. Graft Vessel Disease Following Heart Transplantation: A Systematic Review of the Role of Statin Therapy. World Journal of Surgery. 2014;38(9):2324–34. DOI: 10.1007/s00268-014-2543-x

4. Wenke K, Meiser B, Thiery J, Nagel D, Von Scheidt W, Krobot K et al. Simvastatin Initiated Early After Heart Transplantation: 8-Year Prospective Experience. Circulation. 2003;107(1):93–7. DOI: 10.1161/01.CIR.0000043241.32523.EE

5. Costanzo MR, Costanzo MR, Dipchand A, Starling R, Anderson A, Chan M et al. The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients. The Journal of Heart and Lung Transplantation. 2010;29(8):914–56. DOI: 10.1016/j.healun.2010.05.034

6. Ezhov M.V., Kukharchuk V.V., Sergienko I.V., Alieva A.S., Antsiferov M.B., Ansheles A.A. et al. Disorders of lipid metabolism. Clinical Guidelines 2023. Russian Journal of Cardiology. 2023;28(5):250–97. DOI: 10.15829/1560-4071-2023-5471

7. Kaplan B, Qazi Y, Wellen JR. Strategies for the management of adverse events associated with mTOR inhibitors. Transplantation Reviews. 2014;28(3):126–33. DOI: 10.1016/j.trre.2014.03.002

8. Houde VP, Brûlé S, Festuccia WT, Blanchard P-G, Bellmann K, Deshaies Y et al. Chronic Rapamycin Treatment Causes Glucose Intolerance and Hyperlipidemia by Upregulating Hepatic Gluconeogenesis and Impairing Lipid Deposition in Adipose Tissue. Diabetes. 2010;59(6):1338–48. DOI: 10.2337/db09-1324

9. Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M et al. Efficacy and Safety of Alirocumab in Reducing Lipids and Cardiovascular Events. New England Journal of Medicine. 2015;372(16):1489–99. DOI: 10.1056/NEJMoa1501031

10. Lund LH, Edwards LB, Kucheryavaya AY, Benden C, Christie JD, Dipchand AI et al. The Registry of the International Society for Heart and Lung Transplantation: Thirty-first Official Adult Heart Transplant Report—2014; Focus Theme: Retransplantation. The Journal of Heart and Lung Transplantation. 2014;33(10):996–1008. DOI: 10.1016/j.healun.2014.08.003

11. Alba AC, Foroutan F, Ng Fat Hing NKV, Fan CS, Manlhiot C, Ross HJ. Incidence and predictors of sudden cardiac death after heart transplantation: A systematic review and meta‐analysis. Clinical Transplantation. 2018;32(3):e13206. DOI: 10.1111/ctr.13206

12. Merola J, Jane-wit DD, Pober JS. Recent advances in allograft vasculopathy: Current Opinion in Organ Transplantation. 2017;22(1):1–7. DOI: 10.1097/MOT.0000000000000370

13. Ramzy D, Rao V, Brahm J, Miriuka S, Delgado D, Ross HJ. Cardiac allograft vasculopathy: a review. Canadian Journal of Surgery. 2005;48(4):319–27. PMID: 16149368

14. Asleh R, Briasoulis A, Kremers WK, Adigun R, Boilson BA, Pereira NL et al. Long-Term Sirolimus for Primary Immunosuppression in Heart Transplant Recipients. Journal of the American College of Cardiology. 2018;71(6):636–50. DOI: 10.1016/j.jacc.2017.12.005

15. Kühl M, Binner C, Jozwiak J, Fischer J, Hahn J, Addas A et al. Treatment of hypercholesterolaemia with PCSK9 inhibitors in patients after cardiac transplantation. PLOS ONE. 2019;14(1):e0210373. DOI: 10.1371/journal.pone.0210373