Current treatments for the management of homozygous familial hypercholesterolemia: a systematic review and commentary.

AIMS: Homozygous familial hypercholesterolemia (HoFH) is a rare disorder characterized by markedly elevated circulating low-density lipoprotein cholesterol (LDL-C) from birth. This review aimed to critically evaluate treatments for HoFH with respect to their efficacy, safety, accessibility, overall context and position within the treatment pathway. METHODS: A mixed-methods review was undertaken to systematically identify and characterize primary interventional studies on HoFH, with a focus on LDL-C reduction as the primary outcome. Interventions assessed were ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), lomitapide, evinacumab, with or without LDL apheresis. RESULTS: Twenty-six seminal studies reporting unique patient data were identified. Four studies were randomized controlled trials (RCTs) with the remainder being single-arm trials or observational registries. Data extracted were heterogeneous and not suitable for meta-analyses. Two RCTs, assessed at being low risk of bias, demonstrated PCSK9i were safe and moderately effective. An RCT demonstrated evinacumab was safe and effective in all HoFH subgroups. Lomitapide was reported to be efficacious in a single-arm trial, but issues with adverse events, tolerability, and adherence were identified. An RCT on ezetimibe showed it was moderately effective when combined with a statin. LDL apheresis was reported as effective, but its evidence base was at very high risk of bias. All interventions lowered LDL-C, but the magnitude of this, and certainty in the supporting evidence, varied. CONCLUSION: In practice, multiple treatments are required to treat HoFH. The sequencing of these should be made on an individualized basis, with consideration made to the benefits of each intervention.

Homozygous familial hypercholesterolaemia (HoFH) is a rare genetic disorder that results in elevated cholesterol levels, which can cause premature cardiovascular events such as heart attacks and stroke. We performed a literature review to systematically identify and analyse studies reporting on newer treatments for HoFH which lower cholesterol levels, focussing on the overall advantages and disadvantages of each treatment. We identified 26 studies, including clinical trials and observational research, reporting on the interventions ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), lomitapide, evinacumab, and LDL apheresis. While all treatments showed promise in reducing cholesterol levels, none were sufficient to effectively treat HoFH on their own, and often the confidence in the results were limited by the methodological weaknesses of the studies. The evidence suggests that management of HoFH requires an individualized approach, with consideration given to the efficacy, safety, tolerability and accessibility of each treatment.

Correlation between bradykinin concentration and blood pressure during Rheocarna therapy: A single-center case series.

INTRODUCTION: A novel LDL (low-density lipoprotein) apheresis therapeutic option, Rheocarna, has garnered attention as an alternative therapy for chronic limb-threating ischemia (CLTI). Bradykinin-mediated vasodilation is involved in the effects of LDL apheresis and a decrease in blood pressure (BP), but the changes in bradykinin concentration during Rheocarna therapy are unknown. METHODS: The study involved patients with CLTI treated with Rheocarna at our hospital, from April 2022 to August 2023. RESULTS: After Rheocarna therapy, skin ulcers improved in 80% of the patients. Circuit coagulation was observed in two patients with high fibrinogen levels. A decrease in BP was observed at approximately the same time when the bradykinin concentration peaked. The peak bradykinin concentration in a patient undergoing hemodialysis at the same time was considerably lower than that in the other patients. CONCLUSION: This is the first report on the changes in bradykinin concentration under Rheocarna therapy.

Updated evidence of beneficial effect of LDL apheresis for refractory nephrotic syndrome due to a variety of causative diseases for nationwide and global approval.

Low-density lipoprotein apheresis (LDL-A) therapy has shown reasonable efficacy in treating nephrotic syndrome (NS) refractory to initial drug therapy and has been covered by National Health Insurance for the indication of drug-resistant focal segmental glomerulosclerosis (FSGS) since 1992 in Japan and has contributed to liberating substantial number of patients of this disease from entering into end-stage renal disease by easier practical application in actual clinical settings. Subsequently, various beneficial evidence of this treatment has accumulated on those other than FSGS, however, due to the limitation of covered disease insurance only for FSGS, patients with diseases other than FSGS are unlikely to benefit from this treatment in practice. This review summarizes the therapeutic evidence of the beneficial effect of LDL-A accumulated to date and the mechanisms of action analyzed from multifaceted perspectives. examines the applicability of expanding insurance coverage for diseases other than FSGS.

Short term-efficacy and tolerability of Rheocarna, a novel direct hemoperfusion adsorptive column, for chronic limb-threatening ischemia in dialysis patients: A single-center case series.

INTRODUCTION: With population aging and lifestyle changes, the number of patients with chronic limb-threatening ischemia (CLTI) is increasing, and refractory or recurrent lesions are more common, especially in chronic dialysis patients. In March 2021, a new type of adsorptive cellulose bead column immobilized with dextran sulfate and L-tryptophan for direct hemoperfusion (DHP) was approved by Japan's medical insurance system as a treatment for CLTI. METHODS: We retrospectively analyzed 17 cases of CLTI in dialysis patients treated with DHP using the novel column (Rheocarna) (DHP-R) at our hospital from May 2021 to October 2022. The short-term of efficacy of DHP-R was judged qualitatively by the foot care team every 2 weeks based on the assessment of skin color, warmth, ulcer epithelialization or shrinkage of the ulcer area, and foot pain. The final judgment of efficacy was made after the final DHP-R session. RESULTS: The median age of patients was 66 years, the median dialysis duration was 10 years, 15 cases (88%) were male, and 15 cases (88%) had diabetes. The median total number of sessions was eight. In comparing the groups in which DHP-R was effective and ineffective, there was no significant difference in any factors including patient background data (i.e., age, diabetes, low-density lipoprotein cholesterol, hemoglobin, dialysis duration, etc.), type of anticoagulants, and presence of episodes of blood pressure drop or circuit clotting during session. Three cases with symptomatic hypotension during the session and two cases with circuit clotting that did not improve with increased heparin dose all resolved immediately after changing the anticoagulant from heparin to nafamostat mesylate (NM). CONCLUSION: Identification of patients' characteristics in which DHP-R is favorable and some reliable index that allow a rapid decision to continue DHP-R are needed. In addition, validating whether the use of NM as anticoagulant affects the efficacy of DHP-R for CTLI treatment remains a challenge to resolve.

The Characteristics of Dialysis Membranes: Benefits of the AN69 Membrane in Hemodialysis Patients.

Patients undergoing hemodialysis (HD) experience serious cardiovascular complications, through malnutrition, inflammation, and atherosclerosis. Amputation for peripheral arterial disease (PAD) is more prevalent in patients undergoing HD than in the general population. In addition, revascularization procedures in dialysis patients are often associated with subsequent amputation and high mortality rates. To improve the prognosis of dialysis patients, malnutrition and inflammation must be properly treated, which necessitates a better understanding of the characteristics of dialysis membranes. Herein, the characteristics of several dialysis membranes were studied, with a special reference to the AN69 membrane, noting several similarities to low-density lipoprotein (LDL)-apheresis, which is also applicable for the treatment of PAD. Both systems (LDL-apheresis and AN69) have anti-inflammatory and anti-thrombogenic effects because they use a negatively charged surface for extracorporeal adsorptive filtration from the blood/plasma, and contact phase activation. The concomitant use of both these therapeutic systems may have additive therapeutic benefits in HD patients. Here, we reviewed the characteristics of dialysis membranes and benefits of the AN69 membrane in dialysis patients.

The fluctuation of skin perfusion pressure in hemodialysis patients treated with LDL apheresis therapy: A comparison of LDL adsorption and double filtration plasmapheresis.

BACKGROUND: There have been a number of reports suggesting that LDL apheresis, including LDL adsorption and double filtration plasmapheresis (DFPP), can be applied for the treatment of lower extremity peripheral arterial disease (PAD) in hemodialysis patients, whereas there is no definitive recommendation for the use of LDL apheresis. STUDY DESIGN: The change of skin perfusion pressure (SPP) during LDL apheresis was measured in every single treatment to determine the effect of LDL adsorption and DFPP on improving blood flow in lower extremity PAD hemodialysis patients. Eleven hemodialysis patients treated with more than two series of LDL apheresis were involved in the study. "One series" included 10 treatments of LDL apheresis according to the Japanese health care insurance system. RESULTS: In total, 320 treatments (32 series) of LDL apheresis were performed utilizing either LDL adsorption or DFPP treatment in 11 patients. The SPP values pre- and post-apheresis were recorded in 315 treatments (228 LDL adsorption and 87 DFPP). The SPP was significantly improved after both LDL adsorption (P < .001) and DFPP (P = .002) treatment. The median change of SPP was significantly larger in the LDL adsorption group (12.6 mm Hg, range: -48.5, 77.0 mm Hg) than in the DFPP group (6.7 mm Hg, range: -42.0, 72.5 mm Hg) (P = .003). The LDL adsorption consistently offered a significant increase in the SPP, whereas DFPP treatment seemed to have modest effects on the improvement of SPP compared to the LDL adsorption. CONCLUSIONS: These data indicate that LDL adsorption should be considered the primary LDL apheresis therapy for lower extremity PAD in hemodialysis patients to achieve improvement of blood flow.

Pregnancy in homozygous familial hypercholesterolemia-A case series.

INTRODUCTION: Familial hypercholesterolemia (FH) is an autosomal codominant lipid metabolism disorder. It results in lifelong elevation of plasmatic low-density lipoprotein cholesterol (LDL-C) levels, followed by premature atherosclerosis. In women, pregnancy and lactation represent an additional risk due to association of physiological changes, pre-existing dyslipidemia, and limited therapeutic possibilities and experiences. Methods of extracorporeal LDL-apheresis represent a suitable therapeutic approach. CASE SERIES: We present our experience in case reports of six HoFH women and their 13 pregnancies (nine successful, three abortions, and one interruption). One patient experienced a lethal complication of her pregnancy. Of the nine successful pregnancies, two cases were treated by LDL-apheresis. CONCLUSION: Pregnancy in HoFH women represents substantial risk; however, patients without signs of decompensated cardiovascular disease can have a good prognosis. LDL-apheresis plays an important role in the management of pregnancy in HoFH.

The Importance of Arterial Stiffness Assessment in Patients with Familial Hypercholesterolemia.

Cardiovascular diseases are still the leading cause of mortality due to increased atherosclerosis worldwide. In the background of accelerated atherosclerosis, the most important risk factors include hypertension, age, male gender, hereditary predisposition, diabetes, obesity, smoking and lipid metabolism disorder. Arterial stiffness is a firmly established, independent predictor of cardiovascular risk. Patients with familial hypercholesterolemia are at very high cardiovascular risk. Non-invasive measurement of arterial stiffness is suitable for screening vascular dysfunction at subclinical stage in this severe inherited disorder. Some former studies found stiffer arteries in patients with familial hypercholesterolemia compared to healthy controls, while statin treatment has a beneficial effect on it. If conventional drug therapy fails in patients with severe familial hypercholesterolemia, PCSK9 inhibitor therapy should be administered; if these agents are not available, performing selective LDL apheresis could be considered. The impact of recent therapeutic approaches on vascular stiffness is not widely studied yet, even though the degree of accelerated athero and arteriosclerosis correlates with cardiovascular risk. The authors provide an overview of the diagnosis of familial hypercholesterolemia and the findings of studies on arterial dysfunction in patients with familial hypercholesterolemia, in addition to presenting the latest therapeutic options and their effects on arterial elasticity parameters.

The Role of Endothelial Progenitor Cells in Atherosclerosis and Impact of Anti-Lipemic Treatments on Endothelial Repair.

Cardiovascular complications are associated with advanced atherosclerosis. Although atherosclerosis is still regarded as an incurable disease, at least in its more advanced stages, the discovery of endothelial progenitor cells (EPCs), with their ability to replace old and injured cells and differentiate into healthy and functional mature endothelial cells, has shifted our view of atherosclerosis as an incurable disease, and merged traditional theories of atherosclerosis pathogenesis with evolving concepts of vascular biology. EPC alterations are involved in the pathogenesis of vascular abnormalities in atherosclerosis, but many questions remain unanswered. Many currently available drugs that impact cardiovascular morbidity and mortality have shown a positive effect on EPC biology. This review examines the role of endothelial progenitor cells in atherosclerosis development, and the impact standard antilipemic drugs, including statins, fibrates, and ezetimibe, as well as more novel treatments such as proprotein convertase subtilisin/kexin type 9 (PCSK9) modulating agents and angiopoietin-like proteins (Angtpl3) inhibitors have on EPC biology.

Liposorber® LA-15 system for LDL apheresis in resistant nephrotic syndrome patients.

BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) is a major cause of stage 5 chronic kidney disease (CKD 5) in children. LDL apheresis (LDL-A) is now FDA approved for the treatment of pediatric focal segmental glomerulosclerosis (FSGS). Effective management of hyperlipidemia with LDL-A in SRNS patients may prevent progression of kidney disease and lead to remission. We report a case series of patients who received LDL-A for treatment of SRNS METHODS: We describe five children with SRNS who were treated with 12 sessions of LDL-A. Partial remission (PR) is defined as urine protein to creatinine ratio (UPC) of 0.2-2 (g/g) or decrease in UPC ≥ 50%, and complete remission (CR) is defined as UPC < 0.2 (g/g). RESULTS: One patient achieved CR and three achieved PR. One patient did not respond to therapy. The earliest that a patient achieved PR was at treatment #10 and some did not respond until after LDL-A was completed. Those who responded stayed in either CR or PR for extended periods of time. LDL-A was successful at significantly reducing LDL (p < 0.001), total cholesterol (p < 0.001), and triglyceride (p < 0.001). CONCLUSIONS: LDL-A was able to significantly decrease the lipid levels in these patients and induce CR and PR in the majority. The current study confirms previous studies showing those with a higher glomerular sclerosis burden were less likely to respond. LDL-A should be considered in patients with treatment-resistant SRNS and should be considered before there is a high burden of glomerular sclerosis to provide the best chance of success.

Favorable therapeutic efficacy of low-density lipoprotein apheresis for nephrotic syndrome with impaired renal function.

Many reports have shown the therapeutic efficacy of LDL apheresis (LDL-A) in drug-resistant nephrotic syndrome (NS) for improvement of heavy proteinuria and severely impaired renal function. To obtain comprehensive results in a large number of cases, a post hoc analysis of the Prospective Observational survey on the Long-Term Effects of the LDL-Apheresis on the Drug Resistant Nephrotic Syndrome (POLARIS) study was performed by stratifying enrolled cases according to the pretreatment estimated glomerular filtration rate (eGFR) levels indicating normal (N) (≥60 ml/min/1.73 m2 ), moderately impaired (M) (≥30 to <60 ml/min/1.73 m2 ), and severely impaired (S) (<30 ml/min/1.73 m2 ) renal function. Significant improvements of proteinuria and renal function were found in Group N and, most interestingly, in Group M. A tendency for improvement in proteinuria was found in Group S. Most cases in all groups had not entered end-stage renal disease at 2 years after LDL-A treatment. These results suggest that LDL-A has therapeutic efficacy even in cases in which renal function has declined to 30 ml/min/1.73 m2 .

Efficacy of LDL apheresis for the treatment of cholesterol crystal embolism: A prospective, controlled study.

This study was performed to evaluate the efficacy and safety of LDL apheresis (LDL-A) for the treatment of cholesterol crystal embolism (CCE) after cardiovascular procedures. We conducted a prospective multicenter study of 34 patients with CCE and 15 historical control patients. The present participants underwent six sessions of LDL-A for 4 weeks and underwent medical therapy with corticosteroids and statins. The mean creatinine concentration and estimated glomerular filtration rate at baseline were 3.82 ± 2.29 mg/dL and 17.8 ± 9.9 mL/min/1.73 m2 , respectively. The prevalence of maintenance dialysis at 24 weeks was significantly lower in the present participants than in the historical controls (3.1% vs. 40.0%, respectively; p < 0.0001), but the mortality rate at 24 weeks was comparable (19% vs. 33%, respectively). Although 45 adverse events occurred in 23 participants, there were no unexpected adverse events. LDL-A for CCE reduces the prevalence of maintenance dialysis 24 weeks later and is well tolerated. This study was registered in the Japan Registry of Clinical Trials (jRCTs022180029) and clinicaltrials.gov (NCT01726868).

An Autopsy Case of Acute Pancreatitis Caused by Cholesterol Crystal Embolization.

Cholesterol crystal embolization (CCE) shows a poor prognosis and it can cause ischemic organ damage due to a cholesterol embolism from atherosclerotic lesions in large blood vessels. Such an embolism mainly affects the kidneys and skin, although cases involving digestive organs have also been reported. We encountered an autopsy case of CCE with damage mainly to the digestive organs, including the pancreas. The patient had non-specific abdominal symptoms or image findings. Symptomatic therapy failed to save him. CCE can involve the digestive organs, and so must be differentiated from abdominal pathologies. Moreover, conventional treatments may be ineffective, and new treatments might thus be necessary.

Case Report: Liver Transplantation in Homozygous Familial Hypercholesterolemia (HoFH)-Long-Term Follow-Up of a Patient and Literature Review.

Homozygous familial hypercholesterolemia (HoFH) is a rare inherited metabolic disorder, frequently leading to an early cardiovascular death if not adequately treated. Since standard medications usually fail to reduce LDL-cholesterol (LDL-C) levels satisfactorily, LDL-apheresis is a mainstay of managing HoFH patients but, at the same time, very burdensome and suboptimally effective. Liver transplantation (LT) has been previously shown to be a promising alternative. We report on a 14 year-long follow-up after LT in a HoFH patient. At the age of 4, the patient was referred to our institution because of the gradually increasing number of xanthomas on the knees, elbows, buttocks, and later the homozygous mutation c.1754T>C (p.Ile585Thr) on the LDL-receptor gene was confirmed. Despite subsequent intensive treatment with the combination of diet, statins, bile acid sequestrant, probucol, and LDL-apheresis, the patient developed valvular aortic stenosis and aortic regurgitation by 12 years. At 16 years, the patient successfully underwent deceased-donor orthotopic LT. Nine years post-LT, we found total regression of the cutaneous xanthomas and atherosclerotic plaques and with normal endothelial function. Fourteen years post-LT, his clinical condition remained stable, but LDL-C levels have progressively risen. In addition, a systematic review of the literature and guidelines on the LT for HoFH patients was performed. Six of the 17 identified guidelines did not take LT as a treatment option in consideration at all. But still the majority of guidelines suggest LT as an exceptional therapeutic option or as the last resort option when all the other treatment options are inadequate or not tolerated. Most of the observed patients had some kind of cardiovascular disease before the LT. In 76% of LT, the cardiovascular burden did not progress after LT. According to our experience and in several other reported cases, the LDL-C levels are slowly increasing over time post LT. Most of the follow-up data were short termed; only a few case reports have followed patients for 10 or more years after LT. LT is a feasible therapeutic option for HoFH patients, reversing atherosclerotic changes uncontrollable by conservative therapy, thus importantly improving the HoFH patient's prognosis and quality of life.

The effect of DALI lipid apheresis in the prognosis of homozygous familial hypercholesterolemia: Seven patients' experience at a DALI apheresis center.

INTRODUCTION: Familial hypercholesterolemia (FH) is characterized by severe hypercholesterolemia that can result in coronary artery disease occurring at an early age. If patients are not cured with lipid-lowering drugs and diets, lipid apheresis may be an effective treatment option in these cases. Here, we evaluate the efficacy, selectivity and safety of the DALI apheresis technique. MATERIALS AND METHODS: Seven pediatric patients (2 girls; 5 boys) with ages between 7 and 14 years (mean age: 6.5±2.1 years) with HFH were included in this study. We restrospectively evaluated clinical and laboratory findings. We used the DALI system for lipid apheresis concomitant with medical treatment and diet for hyperlipidemia. RESULTS: The cohort's mean T.cholesterol level prior to apheresis was 700.57±136.36 mg/dl,the mean LDL-C value was 526.86±131.56 mg and the mean HDL-C level was 36.57±4.58 mg/dl.The mean cholesterol levels after apheresis were consecutively 317.57±93.70 /257.29±90.38 / 33.36±4.78 mg/dl.We noted a 51.1% reduction in LDL-C level and an 8.7% reduction in HDL-C level in our apheresis sessions.The reduction in LDL-C was statistically significant (p<0.05). During 1025 apheresis therapy, the most frequent mild and moderate adverse events were deviceaccess problems and hypotension (in all patients);severe adverse events were mainly due to cardiac problems(myocardial infarct and arrhythmia) and hypotension. CONCLUSION: Lipid apheresis is an inevitable alternative treatment for HFH. Despite all of its application problems, DALI system is an effective therapy for decreasing atherogenic lipids from circulation.

Low-density lipoprotein apheresis for PLA2R-related membranous glomerulonephritis accompanied by IgG4-related tubulointerstitial nephritis.

IgG4-related disease preferentially involves the kidney by tubulointerstitial nephritis with IgG4-positive plasma cell filtration and/or membranous glomerulonephritis. We reported the case of a 68-year-old man with IgG4-related tubulointerstitial nephritis combined with antiphospholipase A2 receptor (PLA2R)-related membranous glomerulonephritis, in which distinguishing between idiopathic PLA2R-related and IgG4-related secondary membranous glomerulonephritis was difficult. We diagnosed him as having IgG4-related disease, based on a serum IgG4 level of 170 mg/dL and the presence of IgG4-related parotiditis. On renal biopsy, there was tubulointerstitial nephritis with IgG4-positive plasma cell filtration, which was compatible with IgG4-related disease and membranous glomerulonephritis, with concomitant positive staining for PLA2R on immunofluorescence microscopy. The renal function immediately recovered after steroid treatment, probably because of the improvement in the tubulointerstitial lesions, but his nephrotic syndrome was steroid-resistant. Low-density lipoprotein (LDL) apheresis therapy was effective for membranous glomerulonephritis and increased his serum albumin from 1.4 to 2.8 g/dL. Although IgG4-related kidney disease usually accompanies secondary membranous glomerulonephritis, the positive PLA2R staining suggested a concomitant primary membranous glomerulonephritis. The recent treatment strategy, including LDL apheresis, for primary and secondary membranous glomerulonephritis was discussed briefly in this report.

Mental status and physical activity in patients with homozygous familial hypercholesterolemia: A subgroup analysis of a nationwide survey (A-HIT1 registry).

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare, life-threatening disease due to high serum low-density lipoprotein (LDL) cholesterol levels. LDL cholesterol-lowering interventions are fundamental for patients with HoFH. OBJECTIVE: It was aimed to investigate the association between the mental status of patients with HoFH and healthy lifestyle behaviors. METHODS: This subgroup analysis of the A-HIT1 population included the data of patients aged ≥18 years with a clinical diagnosis of HoFH undergoing therapeutic LDL apheresis. Besides the demographic and clinical characteristics of patients, healthy lifestyle behaviors were assessed, and psychiatric symptoms were screened by Symptom Check List (SCL-90-R). RESULTS: The highest percentage for pathology was observed in dimensions of obsessive-compulsive, somatization, interpersonal sensitivity, and depression in SCL-90-R. Patients with any cardiovascular condition have more psychiatric symptoms in different fields of SCL-90-R. The outcomes of the correlative analysis indicated that lower the age of the first coronary event better the psychiatric status, probably denoting a better adaptation to disease and its treatment. Among 68 patients, 36 patients were not exercising regularly. Patients with regular physical activity had significantly lower scores in most dimensions of SCL-90-R and there was no association between regular physical activity and other investigated variables. The strongest predictor of regular exercising was global severity index of SCL-90-R. CONCLUSION: In the HoFH population, there was a high prevalence of mental disturbances. Better psychiatric status was associated with regular exercising. Therefore, assessing the mental status of patients with HoFH and referring patients in need, to a psychiatrist, may improve the outcome of patients.

Lomitapide treatment in a female with homozygous familial hypercholesterolaemia: a case report.

BACKGROUND: Homozygous familial hypercholesterolaemia (FH) is an autosomal-dominant inherited disease presenting with highly elevated low-density lipoprotein cholesterol (LDL-C) levels. Untreated, the patient can develop atherosclerosis and cardiovascular disease already in adolescence. Treatment with statins and ezetimibe is usually not sufficient and LDL apheresis is often required. Lomitapide, an inhibitor of the microsomal triglyceride transfer protein, reduces LDL-C and triglyceride levels and can be used alone or in combination with other therapies in homozygous FH. However, experience with this agent is still limited. CASE SUMMARY: We present a young female who was diagnosed with homozygous FH at 6 years of age. She shows a complete lack of normal LDL receptor activity and no cholesterol-lowering effect from statins. The patient was treated with LDL apheresis from 7 years of age. When LDL apheresis treatment extended to twice a week, she began to experience adverse effects, including catheter-related complications, infections, and hospital admissions. When lomitapide treatment was initiated, the frequency of apheresis reduced, the LDL-C levels improved and she has not had any further hospital admissions since. Initially, she suffered from gastrointestinal disturbances. However, after 3 years of treatment with lomitapide 20 mg/day, the patient has not experienced any adverse effects. DISCUSSION: In this female with homozygous FH adding lomitapide treatment to LDL apheresis has contributed to improved LDL-C levels, a reduction in LDL apheresis sessions and enhanced quality of life. No adverse effects have been reported. These findings suggest that lomitapide can be a drug of choice in patients with homozygous FH.

PCSK9 Inhibition: New Treatment Options and Perspectives to Lower Atherogenic Lipoprotein Particles and Cardiovascular Risk.

PURPOSE OF REVIEW: To summarize latest clinical studies and to put them into perspectives for clinical relevant subgroups and new therapeutic options. RECENT FINDINGS: Have investigated PCSK9 inhibitors in patients with very high cardiovascular risk and insufficient LDL cholesterol lowering under current maximal tolerated lipid-lowering therapy, patients with statin intolerance, or genetic forms of familiar hypercholesterolemia, and patients on LDL apheresis. Purpose of recent cardiovascular endpoint trials has proven cardiovascular benefit of this new approach. PCSK9 inhibition with fully humanized antibodies has proven to be effective, safe, and well-tolerated in reducing cardiovascular risk by LDL cholesterol lowering. Therefore, research interests are to elucidate additional roles and effects of PCSK9 modulation on inflammation and cellular processes of the atherosclerotic plaque and to develop alternative therapeutic strategies addressing PCSK9 as a proven and therefore promising drug target.