A study in high-risk, maximally pretreated patients to determine the potential use of PCSK9 inhibitors at various thresholds of total and LDL cholesterol levels

Abstract

Abstract:Purpose of the study:Statins and ezetimibe reduce low density lipoprotein cholesterol (LDL-c) and cardiovascular disease (CVD) risk. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors lower LDL-c by 50-70% and might be useful in refractory patients. The National Institute for Health and Care Excellence (NICE) technology appraisal guidance (TAG) recommends use of these drugs in secondary prevention and familial hypercholestrolaemia (FH) at differing LDL-c thresholds. We have estimated the proportion of patients in whom this third-line drug might be useful. Study Design:We used data from a lipid lowering audit programme to study 72 with FH and/or CVD of 271 patients referred over 12 months who failed to achieve target total cholesterol (TC) and LDL-c levels. All 72 patients were treated with ezetimibe, 69 cases also received statins. We used LDL-c thresholds 1.5-5.5mmol/l to estimate how many of these refractory patients could benefit from PCSK9 inhibitors. Results:In the 72 patients, TC and LDL-c targets were not met by 64 and 53 patients respectively. We judged using the NICE TAG, that only 1 patient (1.4% ezetimibe requiring and 0.4% total referrals) required a PCSK9 inhibitor. Conclusion:We determined that the proportion of patients eligible for a PCSK9 inhibitor at various TC and LDL-c levels is modest. This may reflect the use of all available statins in UK lipid clinics often at non-daily frequency. We suggest that cost effective use of PCSK9 inhibitors requires prescribing being restricted to clinicians working in specialised lipid clinics. Introduction:

Assessment of serum proprotein convertase subtilisin/kexin type 9 in pediatric sepsis syndrome

“…PCSK9 is involved in the degradation of the low-density lipoprotein receptor (LDLR) and the modulation of intracellular and plasma cholesterol levels, as the binding of PCSK9 to LDLR prevents the removal of LDL particles from the blood plasma 14 .…”