Treatment of hypercholesterolaemia with PCSK9 inhibitors in patients after cardiac transplantation

Background Hypercholesterolaemia is common in patients after cardiac transplantation. Monoclonal antibodies that inhibit proprotein convertase subtilisin-kexin type 9 (PCSK9) reduce low-density lipoprotein (LDL) cholesterol levels and subsequently the risk of cardiovascular events in patients with dyslipidaemia. There are no published data on the effect of this medication class on cholesterol levels in patients after cardiac transplantation. Methods In this retrospective study we investigated patients who were treated with PCSK9 inhibitors either because of intolerance of statins or residual hypercholesterolaemia with evidence of cardiac allograft vasculopathy. We compared the data of patients prior to the start with these medications with their most recent dataset. Results Ten patients (nine men; mean age 58 +/- 6 years) underwent cardiac transplantation 8.3 +/- 4.5 (range 3-15) years ago. The treatment duration of Evolocumab or Alirocumab was on average 296 +/- 125 days and lead to a reduction of total Cholesterol (281 +/- 52 mg/dl to 197 +/- 36 mg/dl; p = 0.002) and LDL Cholesterol (170 +/- 22 mg/dl to 101 +/- 39 mg/dl; p = 0.001). No significant effects on HDL Cholesterol, BNP, Creatin Kinase or hepatic enzymes were noticed. There were no unplanned hospitalisations, episodes of rejections, change of ejection fraction or opportunistic infections. Both patients on Alirocumab developed liver pathologies: One patient died of hepatocellular carcinoma and the other developed hepatitis E. Conclusions Our study demonstrates that the PCSK9 inhibitors Evolocumab and Alirocumab lead to a significant reduction of LDL Cholesterol in heart transplantation recipients. No effect on cardiac function or episodes of rejections were noticed. Larger and long-term studies are needed to establish safety and efficacy of PCSK9 inhibitors after cardiac transplantation.