Treatment of Therapy-Resistant Hyperlipidaemia after Heart Transplant with PCSK9-Inhibitors

Abstract

Purpose Hyperlipidemia is a major factor in the development of graft vasculopathy (GVP) after heart transplant. The incidence of hyperlipidaemia in heart transplant (HTX) patients under immunosuppressive therapy is 74% in the first year, and 91% in the first five years. Lipid-lowering therapy with statins presents a great challenge due to interactions and adverse effects. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have already proven very effective in high-risk cardiovascular patients. In our centre, PCSK9-inhibitors have been administered to selected HTX-patients, in which the target LDL-Cholesterol of 100mg/dl could not be reached with reasonable doses of statins and/or Etizimib. Methods In the period 02/2017 to 06/2018, 15 adult HTX-patients (median age 55.3, (25-75%: 48.2-64.6), 25% female) were selected. The patients were at a median of 35.1 (25-75%: 28.4-78.6) months post-HTX. The selected patients were evaluated together in the lipid clinic (licenced for PCSK9-inhibitors). Therapy was initiated with Alirocumab 75mg. Statin-therapy was changed and appropriately documented when changes in lipid-parameters and/or adverse effects occurred. In order to evaluate incidence and prevalence of myopathy and hepatotoxicity, CK and liver enzymes and were measured 1, 3, 6, 9, 12, and 15 months post conversion. Analysis of effectiveness were conducted by measuring blood lipids (LDL-C, HDL, total cholesterol, triglycerides, and LP(a)). Results Total cholesterol (231 (198-245) vs. 151 (139-175) mg/dl; p Conclusion Therapy with PCSK9-inhibitors (Alirocumab) constitutes an effective and safe option in therapy of hyperlipidaemia after heart transplant. Under treatment liver and kidney parameters stayed stable, while a significant reduction of lipid levels could be achieved. To evaluate the long-term effects of PCSK9-Inhibitors longer observation period is necessary.