It is thought that immunological factors, like histocompatibility mismatch, acute rejection episodes and chronic inflammation play an important role in the development of CAV

It is thought that immunological factors, like histocompatibility mismatch, acute rejection episodes and chronic inflammation play an important role in the development of CAV. to the start with these medications with their most recent dataset. Results Ten patients (nine men; mean age 586 years) underwent cardiac transplantation 8.34.5 (range 3C15) years ago. The treatment duration of Evolocumab or Alirocumab was on average 296125 days and lead to a reduction of total Cholesterol (28152 mg/dl to 19736 mg/dl; p = 0.002) and LDL Cholesterol (17022 mg/dl to 10139 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 Kinesore 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. Introduction Hypercholesterolaemia is common in patients after cardiac transplantation affecting over 90% of patients 5 years post transplantation [1]. The immunosuppressive regime, systemic inflammation and the metabolic syndrome are some factors that are linked to the development of hypercholesterolaemia. Statin therapy has been shown to improve survival of transplanted patients and has been implicated in reducing fatal rejections, decreasing terminal cancer risk and reducing the risk of cardiac allograft vasculopathy (CAV) [2]. It has therefore received a class I treatment recommendation irrespective of cholesterol levels after transplantation [3]. However, some patients cannot tolerate statins or have residual hypercholesterolaemia despite treatment with a statin. Evolocumab and Alirocumab are monoclonal antibodies that inhibit hepatic proprotein convertase subtilisin-kexin type 9 (PCSK 9) and as such are increasing available low-density lipoprotein (LDL) cholesterol receptors on hepatocytes. PCSK9 inhibitors have been shown to not only reduce low-density lipoprotein (LDL) cholesterol levels in patients with hyperlipidaemia [4C6], but also lower the risk of cardiovascular events in patients with established cardiovascular disease [7, Rabbit Polyclonal to ENTPD1 8]. There are no published data on the effect of PCSK9 inhibitors on cholesterol levels in patients after cardiac or other solid organ transplantation. Therefore we sought to determine whether PCSK9 inhibitors are able to reduce cholesterol levels in patients after Kinesore cardiac transplantation similar to non-transplanted patients. We also planned to assess the frequency of rejection as well as cardiac function during treatment. Methods The Ethic Review Board of the University of Leipzig has approved this study (Local ethical review board number: 399/17-ek). No consent was obtained as the data was analysed anonymously. All patients who have been treated with Evolocumab or Alirocumab at our institution either because of intolerance of statins or residual hypercholesterolaemia with evidence of cardiac allograft vasculopathy were investigated in a retrospective study. We compared the data of patients prior to the start with Evolocumab or Alirocumab with their most recent dataset on PCSK9 inhibitor treatment. Statistical analysis All continuous values are reported as mean standard deviation. The descriptive analysis was performed using the Students paired t-test Statistical analyses were performed with SPSS 22.0 software (SPSS Inc, Chicago, IL). A p-value<0.05 was considered statistical significant. Results We identified ten patients with hypercholesterolemia who underwent cardiac transplantation 8.34.5 (range 3C15) years ago (S1 Data). The mean age of the patients were 586 years and nine patients were men. The most common cause for heart failure was dilated cardiomyopathy in six patients, ischaemic cardiomyopathy in three patients and congenital heart disease in one patient. One of the patients had type 2 diabetes mellitus. No patient had known familial hypercholesterolaemia. Prior to PSCK9 therapy five patients had minor rejections (n = 4 1A, n = 1 1B; ISHLT 1990). Cardiac allograft vasculopathy (CAV) was present in seven patients at baseline. The degree was varying from mild CAV in 2 patients (ISHLT CAV 1) to moderate in 3 patients (ISHLT CAV 2) and severe CAV in 2 patients (ISHLT CAV 3). The immunosuppressive regimen consisted of everolimus in most patients (n = 9, Target level: 4C6 ng/ml), mycophenolate mofetil (n = 6, mean dose: 1000 mg b.i.d.), prednisolone (n = 7; mean Kinesore dose: 3.75 mg/day), cyclosporine (n = 2; target level: 25C75 ng/ml) and tacrolimus (n = 2, target level 3C5 ng/ml) (Table 1). Table 1 Baseline characteristics. Baseline characteristics

Ageyrs586Male sexno.9Time after HTXmo104.353.3 (range 42C185)Duration of PCSK9 treatmentdays296125Everolimusno.9MMFno.6Prednisolonno.8TacrolimusCno.2CyclosporinCno.2 Open in a separate window.