The long-term effectiveness and tolerability of PCSK9 inhibitors in a large cardiovascular tertiary centre: A retrospective cohort analysis

Abstract

Background: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are effective LDL-cholesterol–lowering agents used in patients with familial hypercholesterolaemia (FH) and/or very high cardiovascular risk on maximal lipid-lowering therapy. Real-world long-term outcome data from routine clinical practice is of great value but to date there has been scarce data published from within the United Kingdom.

Methods: We performed a retrospective analysis of 364 patients treated with PCSK9 inhibitors in a single tertiary centre lipid clinic. Demographic, clinical, lipid and outcome data were extracted from a prospectively maintained database. Baseline was defined as the value immediately prior to PCSK9i initiation; “current” values represent the most recent measurement on therapy. Descriptive statistics are reported; no formal hypothesis testing was performed.

Results: Mean age at initiation was 62.2 ± 14.8 years; 57% were male. FH was common: 43.6% had primary heterozygous FH and 3.2% had primary homozygous FH. A further 39.7% had non-FH high or very-high cardiovascular risk despite maximal lipid-lowering therapy. Hypertension was present in ~38%, diabetes in ~18%, and ~22% were current or ex-smokers. At least 42% of patients had documented cardiovascular disease events. Baseline mean LDL-cholesterol was 5.61 ± 1.81 mmol/L (n≈360). On treatment, mean LDL-cholesterol fell to 2.37 ± 1.55 mmol/L, corresponding to a mean absolute reduction of 3.26 mmol/L and a mean percentage reduction of 58.7 ± 20.5% (n=352 with paired values). Total cholesterol decreased from 7.86 to 4.56 mmol/L on average. Median follow-up on PCSK9i was approximately 5 years (mean 5.0 ± 1.9 years). At latest follow-up, 304/364 patients (83.5%) remained on PCSK9i. Documented side-effects potentially attributable to PCSK9i occurred in 57 patients (15.7%), most commonly non-specific musculoskeletal symptoms or back pain; discontinuation for adverse events appeared infrequently in the dataset. Major adverse cardiovascular events (MACE) or cardiovascular procedures after PCSK9i initiation were not reliably recorded in in the dataset and therefore the only conclusions that can be made are with regards to lipid lowering effectiveness and tolerability.

Conclusions: In this real-world tertiary lipid clinic cohort, PCSK9 inhibitors produced large, durable reductions in LDL-cholesterol of around 60% over a median of ~5 years, with high treatment persistence and a minimal rate of largely non-serious reported side-effects. The observational design, incomplete event coding and lack of a control group limit inference regarding cardiovascular outcomes, but the lipid-lowering effectiveness is consistent with clinical trial data.