Long-term survival of heFH or ACS patients on PCSK9 targeted therapy based on the real-life data from poland

Background Hypercholesterolemia is the most common and the worst monitored CVD risk factor in Poland and worldwide. PCSK9 targeted therapy, guidelines-recommended in very high CVD risk pts, significantly increases the number of pts on LDL-C goal and reduces CVD and mortality risk. Purpose To analyze data from the National Health Found drug program to see the characteristics of the patients included and long-term efficacy. Methods The B101 reimbursement drug program with PCSK9 inhibitors was launched in Nov. 2018 for heFH pts, since Nov. 2020 also for post-ACS ones, and since Sept. 2022 inclisiran was added. The current inclusion criteria allow to include heFH pts optimally treated with statins and ezetimibe (for ≥3 months) with LDL-C ≥100 mg/dl, and post-MI pts (within last 24 months) with additional CVD risk factors, treated optimally with statins and ezetimibe for ≥3 months and LDL-C ≥70 mg/dl. Results Between Jan. 2019 and 31 Dec. 2024, 2325 pts (men 56%), with 1430 heFH (mean age 54.5 yrs) and 895 ACS pts (61.2 years) were included to the program. 905 pts (39%) started the program with alirocumab, 631 (27.1%) on evolocumab, and 789 (33.9%) on inclisiran. The FH pts are mostly treated with alirocumab (43.1%), next with inclisiran (28.5%) and evolocumab (28.4%), and in ACS pts the most common is inclisiran (42.6%), next alirocumab (32.3%) and evolocumab (25.1%). Mean DCLN score at the program entry in FH pts was 12.13, mean baseline LDL-C 182.4 mg/dl, 35.2% patients were previously treated with lipid apheresis, and 53.5% were treated with high intensity statin (statin intolerance was reported in 11.4% patients). Mean baseline LDL-C in ACS arm was 129.4 mg/dl, 584 (65.3%) were treated intensively at the program entry, and for 21.8% statin intolerance was reported. Mean LDL-C reduction for FH patients within at least 2,5 years follow-up was 67% for alirocumab (mean LDL-C at the end of the follow-up was 67.1 mg/dl) and 61.5% for evolocumab (mean achieved LDL-C 75.5 mg/dl). In ACS patients it was 63% for alirocumab (mean achieved LDL-C 52.5 mg/dl), and 69.2% for evolocumab (LDL-C 48.6 mg/dl) (Fig 1). The number of patients within the first 180 days from the program inclusion that discontinued the therapy or changed the drug were 49 (4%) and 80 (6.5%) in the heFH arm, and 20 (3.1%) and 23 (3.6%) in the ACS arm, respectively. Hospitalization rate for any CVD cause within at least 12 months after starting the program was 16.5 and 38.6% for heFH and ACS arms, respectively, and all-cause mortality for the 6-year follow-up was only 1.5% for FH patients (restricted mean survival time [RMST] was 363.96±0.43 days), and 1.3% for post-MI patients (RMST 362.87±0.81 days) (Fig 2). Conclusions The PCSK9 targeted therapy drug program showed its extremely high effectiveness in the LDL-C reduction with significant mortality reduction, what is a call for immediate action to apply for its extension to other group of patients at high and very high CVD risk.