Persistence with long-term PCSK9 inhibitor treatment and its effectiveness in familial hypercholesterolaemia: data from the SAFEHEART study

Abstract

Aims Most heterozygous familial hypercholesterolemia (FH) patients require intensive lipid-lowering therapy (LLT) including PCSK9 inhibitors (PCSK9i) to reach current LDL-C goals. Persistence with chronic treatment is important to reduce the burden of atherosclerotic cardiovascular disease. We analysed persistence, efficacy, and impact on quality of life of PCSK9i in FH patients in clinical practice setting. Methods and Results Spanish Familial Hypercholesterolemia cohort study (SAFEHEART) is an open, prospective study in genetically defined FH patients in Spain. Patients ≥ 18 years of age (n = 696, 46% females) on stable LLT treated with PCSK9i were analysed. Median LDL-C at starting PCSK9i was 145 mg/dL (IQR, 123-177) [3.8 mmol/L, IQR 3.2-4.6]. After a median follow-up of 3.7 years (IQR, 2.3-4.8), 27 patients (4%) discontinued PCSK9i treatment: 5 temporarily (0.7%) and 22 permanently (3.2%). Persistence with PCSK9i was 96.1% in the whole period. Median LDL-C levels and % LDL-C reduction attained after 1 year of treatment and in the last follow-up visit were 63 mg/dL (IQR, 43-88) [1.6 mmol/L, IQR 1.1-2.23], 61 mg/dL (IQR, 44-82) [1.6 mmol/L IQR, 1.1-2.1 mmol/L], 57.6% (IQR, 39.5-69) and 58% (IQR, 44-68), respectively. 2016 and 2019 ESC/EAS LDL-C goals were attained by 77% and 48% of patients respectively at the last follow-up visit (p < 0.001). Mean QoL score increased slightly in the first year and remained stable. Conclusion Long-term persistence with PCSK9i in FH patients is very high, with a good QoL. Effectiveness in LDL-C reduction and LDL-C goal achievement dramatically improved with PCSK9i in this high-risk population in clinical practice setting.

Prevalence, clinical features and prognosis of familial hypercholesterolemia in Chinese Han patients with acute coronary syndrome after a coronary event: a retrospective observational study

“…It was reported that long-term persistent lipid-lowering therapy with a PCSK9 inhibitor had reduced the burden of atherosclerotic cardiovascular disease to achieve LDL-c goals in high-risk FH patients with ACS in a clinical practice setting [ 7 ]. Few FH patients received intensive combined lipid-lowering treatment containing a PCSK9 inhibitor in the current study.…”

“…Therefore, it is important to accurately diagnose and screen FH in patients with ACS. Long-term lipid-lowering therapy can reduce the burden of atherosclerotic cardiovascular disease in high-risk FH patients with ACS [ 7 – 10 ], but few FH patients can achieve the target LDL-c level of < 1.8 mmol/L and a reduction > 50% from baseline. In addition, FH is an independent risk factor for major adverse cardiovascular and cerebrovascular events (MACCE) in patients after a coronary event during long-term follow-up [ 8 , 11 – 13 ].…”

“…In addition, FH is an independent risk factor for major adverse cardiovascular and cerebrovascular events (MACCE) in patients after a coronary event during long-term follow-up [ 8 , 11 – 13 ]. Thus, it is necessary to optimize the lipid-targeting treatment of patients with FH after a coronary event [ 2 , 7 – 9 , 11 ].…”

Adherence to pharmacotherapy: sine qua non for reducing cumulative risk of premature coronary disease in familial hypercholesterolemia

“…Other studies have also demonstrated low rates of LDL-cholesterol goal attainment in FH [19,20,21 ▪ ]. Likewise, more than 50% of FH patients fail to attain recommended LDL-cholesterol goals even when additionally treated with PCSK9 inhibitors [22 ▪ ]. Poor patient adherence to LLT is the major contributor to the lack of LDL-cholesterol goal attainment [2 ▪▪ ,8 ▪ ].…”

“…Likewise, nonadherence to PCSK9 inhibitors or treatment discontinuation were reported in 20–30% of high-risk patients [31–34]. However, a recent report from the SAFEHEART study showed a high persistence with long-term PCSK9 inhibitor treatment, with only 4% of FH patients discontinuing treatment after a median follow up of 3.7 years [22 ▪ ]. As discussed later, discrepant findings on nonadherence to PCSK9 inhibitors may be reflected by differences in patient and healthcare system related factors that bear on out-of-pocket medication costs.…”