Efficacy and safety of lipid-lowering therapy in liver transplant recipients (the PINTL study): cohort design and baseline characteristics

Aim . To describe the design of the Efficacy and Safety of Pitavastatin and PCSK9 Inhibitors in Liver Transplant Patients (PINTL) study and the baseline clinical and laboratory characteristics of liver transplant recipients with dyslipidemia randomized to receive pitavastatin or a PCSK9 inhibitor (proprotein convertase subtilisin/kexin type 9). Material and methods . This open-label, randomized, prospective, single-center study (PINTL, NCT05537948) enrolled 59 liver transplant recipients randomized 1:1 to pitavastatin (n=30) or a PCSK9 inhibitor (alirocumab/evolocumab, n=29). The study included two following 6-month phases: monotherapy and add-on combination therapy in patients who had not achieved target low-density lipoprotein (LDL) cholesterol (C). Efficacy endpoints included absolute and percentage reductions in LDL-C, the proportion of target level achievement, and the timeframe for achieving and maintaining it. Safety endpoints included the incidence of adverse events, changes in liver enzymes, creatine phosphokinase, and immunosuppressant levels. Results . All patients in the pitavastatin group and 89,7% in the PCSK9 inhibitor group received tacrolimus; 60,0% and 55,2%, respectively, received tacrolimus in combination with everolimus. All patients had high or very high cardiovascular risk; the proportion of patients at very high risk was 33,3% and 20,7%, respectively (p=0,382). Before study inclusion, 20,0% and 13,8% of patients received lipid-lowering therapy, and 13,3% and 0% received statins, respectively. The groups did not differ in most baseline clinical and laboratory parameters. The γ-glutamyl transferase level was higher in the group receiving the PCSK9 inhibitor as follows: 46 (31-103) vs 30 (23-59) U/L (p=0,033). Conclusion . The study cohort had a high cardiovascular risk burden and a low frequency of lipid-lowering therapy prescription. Baseline comparability between the groups will make it possible to evaluate the efficacy and safety of the lipid-lowering strategies studied. The baseline difference in γ-glutamyl transferase levels will be taken into account in further analysis.