First case report of inclisiran therapy in a heart transplant patient

Transplant coronary artery disease (TCAD) represents a severe complication after heart transplantation, modulated by hypercholesterolemia. Management of dyslipidemia in this setting is complex due to interactions between statins and immunosuppressants resulting in an increased risk of rhabdomyolysis and the potential of immunosuppressants themselves to elevate LDL and triglyceride levels. Inclisiran, an mRNA inhibitor of PCSK9, has demonstrated high efficacy without reported pharmacokinetic interactions and a favorable administration regimen. We present the first case of treatment with inclisiran after heart transplantation. We report the case of a 67-year-old male patient who underwent heart transplantation in 2011 with a high cardiovascular risk profile and a history of statin intolerance, treated with ezetimibe. In 2022, due to severe TCAD and elevated LDL-C levels (125 mg/dL), treatment with inclisiran (300 mg on days 0 and 90 and then every 6 months) was initiated in addition to ezetimibe. Lipid and immunosuppressant levels were monitored during follow-up visits. After two doses of Inclisiran, at 6 months, LDL-C was reduced to 69 mg/dL, without side effects or significant alterations in immunosuppressant levels. Subsequently, LDL-C levels showed a further reduction to 31 mg/dL and remained controlled (51 mg/dL and 28 mg/dL in subsequent follow-ups). Despite the reduction in LDL-C, the patient showed progression of TCAD, requiring multiple percutaneous revascularizations. This case suggests the potential value of inclisiran in the treatment of dyslipidemia in heart transplant patients with TCAD, especially in the presence of statin intolerance or risk of drug interactions. The infrequent administration regimen is advantageous in such patients with a high medication burden and can be made to coincide with follow-up visits. However, the progression of TCAD despite LDL-C reduction highlights the multifactorial nature of the disease, with a significant immunological component still not effectively controlled by current preventive therapies.