Persistence to long-term PCSK9 inhibitors treatment and its effectiveness in familial hypercholesterolemia: data from the SAFEHEART study

Abstract Background Most patients with heterozygous familial hypercholesterolemia (FH) do not achieve current LDL-C goals proposed by European guidelines with conventional lipid-lowering therapy (LLT). Chronic use of PCSK9 inhibitors (PCSK9i) have shown to reduce LDL-C levels up to 61% on top of statins. Persistence to chronic LLT is important to reduce the burden of atherosclerotic cardiovascular disease (ASCVD). Purpose To analyze persistence and effectiveness of PCSK9i in clinical practice setting in FH patients from the SAFEHEART register with long-term follow-up. Methods SAFEHEART is an open, long-term prospective study of a cohort of subjects with molecular diagnosis of FH. Follow-up is carried out every year through a standardized phone-call to collect clinical conditions, persistence to medications, lipid profile, and cardiovascular events. This study analyses subjects ≥18 years of age on stable LLT who have received PCSK9i. Results 696 individuals (46% females), median age 56.4 years (IQR 49–66) started with PCSK9i (49% alirocumab and 51% evolocumab). Out of them 38% had history of ASCVD, and 89% were on maximum LLT. Median LDL-C at the moment of starting PCSK9i was 145 mg/dL (IQR, 123–177), representing a poor 2016 & 2019 ESC/EAS guidelines achievement (3% and 0.1% respectively). After a median follow-up of 3.7 years (IQR, 2.3–4.8), 669 patients (96%) remained on PCSK9i treatment during entire follow-up. Only 27 patients (4%) discontinued, 5 temporarily (0.7%) and 22 permanently (3.2%). Most common reasons for PCSK9i treatment interruption were medical decision (n=6), adverse event (AE) (n=5), patient decision not related with AE (n=5) and comorbidity (n=5). Median time to permanent discontinuation was 15 months (IQR, 4–33). Median LDL-C levels observed and % of LDL-C reduction obtained after 1 year of treatment and in the last follow-up visit were: 63 mg/dL (IQR, 43–88), 61 mg/dL (IQR, 44–82), 57.6% (IQR, 39.5–69) and 58% (IQR, 44–68), respectively. 2016 ESC/EAS guidelines LDL-C goals was achieved by 70% of patients at year 1 and 77% in the last follow-up visit after the introduction of PCSK9i (p<0.001). 2019 ESC/EAS goals were achieved by 44.5% and 48% (p=0.1). Conclusion Long-term persistence to PCSK9i treatment in FH patients is very high (96%) and reasons for discontinuation are diverse. This study shows that COVID-19 pandemic did not affected persistence to treatment. Effectiveness in LDL-C reduction and LDL-C goal achievement improved significantly with introduction of PCSK9i in clinical practice setting. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): AMGEN