Evolving trend in the management of heterozygous familial hypercholesterolemia in Italy: A retrospective, single center, observational study.

The effective reduction of LDL-C in patients with heterozygous familial hypercholesterolemia (HeFH) is crucial to reduce their increased cardiovascular risk. Diagnostic and therapeutic (PCSK9 inhibitors) tools to manage HeFH improved in recent years. However, the impact of these progresses in ameliorating the contemporary real-world care of these patients remains to be determined. Aim of this study was to assess the evolution of treatments and LDL-C control in a cohort of HeFH patients in Italy. Four hundred six clinically diagnosed HeFH followed in a single, tertiary lipid centre were included in this survey. Data on lipid levels and medications were collected at baseline and during a median 3-year follow-up. At baseline, 19.8% of patients were receiving conventional high-potency lipid lowering therapies (LLT) and this percentage increased up to 50.8% at last visit. The knowledge of results of molecular diagnosis was associated with a significant increase in treatment intensity and LDL-C lowering. Nevertheless, the new LDL-C target (<70 mg/dl) was achieved only in 3.6% of HeFH patients under conventional LLTs and this proportion remained low (2.9%) also in those exposed to maximal conventional LLT. In 51 patients prescribed with PCSK9 inhibitors, 64.6% and 62.1% reached LDL-C<70 mg/dl at 3- and 12-month follow-up, respectively. Although treatments of HeFH improved over time, LDL-C target achievement with conventional LLT remains poor, mainly among women. The use of molecular diagnosis and even more the prescription of PCSK9i may improve LDL-C control in these patients.

D'Erasmo L ，Commodari D ，Di Costanzo A ，Minicocci I ，Polito L ，Ceci F ，Montali A ，Maranghi M ，Arca M ... -  《-》

Lipoprotein Apheresis and Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Patients With Heterozygous Familial Hypercholesterolemia: A One Center Study.

Kolovou V ，Katsiki N ，Makrygiannis S ，Mavrogieni S ，Karampetsou N ，Manolis A ，Melidonis A ，Mikhailidis DP ，Kolovou GD ... -  《-》

Old challenges and new opportunities in the clinical management of heterozygous familial hypercholesterolemia (HeFH): The promises of PCSK9 inhibitors.

Heterozygous familial hypercholesterolemia (HeFH) is a common (early estimates suggested a prevalence of 1 in 500 individuals, but recent studies have indicated that it may be higher) genetic disorder characterized by markedly elevated plasma concentrations of low-density lipoprotein cholesterol (LDL-C). HeFH is associated with an elevated risk of premature coronary heart disease, stroke, and peripheral vascular disease. Despite the availability of reliable diagnostic criteria (high LDL-C levels, family history or premature CHD and hypercholesterolemia, cerebral/peripheral vascular disease, and the presence of tendon xanthomata or presence of arcus cornealis before age of 45), HeFH is underdiagnosed and undertreated worldwide. Moreover, while there are effective treatments available to decrease LDL-C and prevent early-onset heart disease in individuals with HeFH, because of the high baseline levels of LDL-C, the achievement of target LDL-C levels remains a challenge. In recent years, a number of novel therapies to lower LDL-C levels in HeFH have been developed, including the monoclonal antibodies against serine protease proprotein convertase subtilisin/kexin type 9 (PCSK9), alirocumab and evolocumab, which have the potential to reduce LDL-C by an additional 50%-60% when prescribed in combination with standard lipid-lowering drugs. This review summarizes the challenges in clinical management of subjects with HeFH, with a focus on emerging treatments, and highlights the status of HeFH diagnosis and treatment in Italy.

Arca M 《-》

LDL-cholesterol target achievement in patients with heterozygous familial hypercholesterolemia at Groote Schuur Hospital: Minority at target despite large reductions in LDL-C.

Familial hypercholesterolemia (FH) is characterized by markedly increased LDL-cholesterol (LDL-C) and premature cardiovascular disease (CVD). LDL-C lowering is the cornerstone of therapy. The aim of our study was to evaluate LDL-C target achievement and explore reasons for not reaching target in FH patients attending a public-sector lipid clinic at Groote Schuur Hospital in Cape Town, South Africa. We reviewed clinical records of patients with genetically confirmed heterozygous FH (heFH) retrospectively. For patients seen after 2013, when new guidelines were published, we determined reasons for use of submaximal therapy. Our study population consisted of 776 adult heFH patients. A substantial proportion (41%) of those younger than 50 years of age had already experienced a cardiovascular event. The mean (±SD) untreated and best achieved LDL-C values during follow up were 8.1 ± 2.1 and 4.0 ± 1.5 mmol/l, respectively. Despite a mean LDL-C reduction of 50%, only 140 (25%) achieved an LDL-C ≤ 3.0 mmol/l. Of the 164 participants with follow up after 2013, 42 did not reach LDL-C < 3.0 mmol/l and did not use maximal therapy (26%). The commonest reasons for not using maximum therapy were statin side-effects (n = 15, 36%) and acceptance by the patient (n = 9, 22%) or the physician (n = 8, 19%) of the control achieved. The heFH population in Cape Town is characterized by high baseline LDL-C, a high prevalence of CVD at presentation and low rates of achieving an LDL-C target of 3.0 mmol/l.

van Delden XM ，Huijgen R ，Wolmarans KH ，Brice BC ，Barron JK ，Blom DJ ，Marais AD ... -  《-》

Real-life LDL-C treatment goals achievement in patients with heterozygous familial hypercholesterolemia in the Czech Republic and Slovakia: Results of the PLANET registry.

Despite the high prevalence of familial hypercholesterolemia (FH) and available effective lipid-lowering therapy, most of the individuals with this disorder remain undiagnosed and undertreated. The aim of the PLANET registry was to assess the real-life attainment of low-density lipoprotein cholesterol (LDL-C) therapeutic target level in patients with heterozygous FH, to characterize prescribed lipid-lowering therapy with assessment of its efficiency according to the attainment of the target LDL-C level, and to characterize cardiovascular events observed in this patient population again in relation to LDL-C target level attainment. PLANET registry was designed as a non-interventional, retrospective, cross-sectional, multicentre disease registry for adult patients with heterozygous FH in the Czech Republic and Slovakia. Overall, 1755 patients were enrolled at 32 sites specialized in FH treatment. 15.4% of patients attained the target LDL-C value. The proportion of patients with LDL-C goal achievement increased to 17.3% in the subgroup of patients receiving high-intensity statin therapy (54.6% of study population). Out of 55 patients receiving inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9), 61.8% reached the LDL-C treatment goal. Of all cardiovascular events reported, 14.0% occurred in patients attaining the LDL-C goal, while it was 86.0% in the not-at-target group. It was documented (p=0.004) that the longer is the patient in care at the specialized FH centre, the higher is the probability that he/she will attain the target LDL-C level. Although target LDL-C level attainment remains relatively low, the likelihood of LDL-C goal attainment increases with duration of specialized care.

Vrablik M ，Raslová K ，Vohnout B ，Blaha V ，Satny M ，Kyselak O ，Vaclova M ，Urbanek R ，Maskova J ，Soska V ，Freiberger T ... -  《-》