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Evaluation of plasma-fed lipid apheresis in patients with homozygous familial hypercholesterolaemia
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Abstracts / Atherosclerosis 252 (2016) e1ee196
apheresis was started to selectively remove LDL-C from the plasma.LDL-C levels were measured prior to and after each procedure.C-IMT measurements were performed before the start of apheresis and approximately 1.5 year after performing apheresis. Results: Three HoFH patients were included.Their LDL-C levels before (and after) maximum statin therapy were 20.8 (13.3),16.9 (9.3),and 15.5 (11.2) mmol/L.All patients had extensive cutaneous xanthomas. The mean acute reductions in LDL-C after a single LDL-apheresis session were 77%,74% and 69%.The mean LDL-C levels during a stable period of on average 9 LDL-apheresis sessions were 4.1, 4.7 and 4.0 mmol/dL.Furthermore,a regression of cutaneous xanthomas was observed in all patients.In one patient, c-IMT decreased substantially (0.420 mm to 0.391 mm); c-IMT results for the other two patients did not differ significantly before and after starting LDL-apheresis.LDLapheresis was well tolerated; only mild side effects in 1 patient were reported. Conclusions: Our findings suggest that LDL-apheresis (DSA) in children with homozygous FH is a safe and effective method to lower LDL-C levels, decrease or stabilise c-IMT and to significantly reduce xanthoma size.
EAS16-0584, DYSLIPIDEMIAS: DYSLIPIDEMIAS, SCREENING AND TREATMENT. EVALUATION OF PLASMA-FED LIPID APHERESIS IN PATIENTS WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLAEMIA P. Downie 1, G. Bayly 1, L. Hart 2, S. Douglas 2, J. Griffin 2. 1 University Hospitals of Bristol NHS Foundation Trust, Department of Clinical BIochemistry, Bristol, United Kingdom; 2 University Hospitals of Bristol NHS Foundation Trust, Department of Haematology, Bristol, United Kingdom Objectives: In addition to diet and drug therapy LDL-apheresis is a treatment for Homozygous Familial Hypercholesterolaemia (HoFH). We investigated the use of a Medicollect column, fed plasma from a Terumo Spectra Optia through a Medicap Adasorb Machine to remove LDLcholesterol (LDL-C), in 2 patients with HoFH. Methods: Patient A (27), is a true homozygote, diagnosed with an LDL-C of 27mmol/L at the age of 3 and is treated with LDL-apheresis every two weeks. Patient B (34) is a compound heterozygote, diagnosed aged 11 with an LDL-C of 15mmol/L, currently treated with weekly LDL-apheresis. Previous LDL-apheresis was with Fresenius DALI. 8 procedures were performed for patient A, 12 for patient B. Results: In patient A, mean LDL-C reduction improved from 54 to 65% (p<0.0001) and from 61 to 71% (p<0.0001) in patient B. Subsequently in patient B, we investigated the use of the Fresnius ART universal machine using the Monet programme. 6 procedures were performed; mean LDL-C reduction improved from 61 to 74% (p < 0.0001). On average 15L of whole blood was processed by Monet as opposed to 10L for DALI. Conclusions: Initially there was no patient preference but towards the end of the 6 procedures our preferred Adasorb. The ART Universal machine is also unsuitable for patients with lower body weight due to the higher extra corporeal blood volume required (up to 885mls). However, advantages include its multiple programme selection, its similarity to DALI, its quiet operation, and the fact that it is a compact machine so easy to move/handle and store.
EAS16-0642, DYSLIPIDEMIAS: DYSLIPIDEMIAS, SCREENING AND TREATMENT. LOMITAPIDE IN HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA e FIRST EXPERIENCES IN CLINICAL PRACTICE A. Vogt. Medizinische KLinik 4, Stoffwechselambulanz, Muenchen, Germany Objectives: Lomitapide is a new class of drug to lower LDL-cholesterol (LDL-C) by inhibiting the microsomal transfer protein independently of
LDL-receptors. This might be a unique option for patients with homozygous familial hypercholesterolemia (hoFH). Methods: Four patients with proven hoFH undergoing regular lipoprotein-apheresis were started on Lomitapide in a clinical setting (named patient program). All patients were advised to reduce fat intact and to refrain from alcohol; concomitant medication and apheresis schedule were stable. Results: Two patients had no problems to follow diet instructions. One patient started exercising additionally and lost 20 kg. Pre apheresis LDL-C is reduced markedly. Patient 1: LDL-C -30% (5 mg), -50% (10 mg); patient 2: -47% (5 mg); patient 3: -24% (5 mg); patient 4: -30% (5 mg). In patient 1 apheresis frequency was reduced from every week to every two weeks. Dose increasing had to be delayed in two patients due to mild gastrointestinal symptoms. Liver enzymes increased in patient 1 due to alcohol intake and decreased with abstinence. Conclusions: Low dose Lomitapide reduced LDL-C markedly and treatment goals may be reached in the course of treatment for the first time in these patients with extreme LDL-C-levels. Necessity for lipoprotein-apheresis might be reduced. Lomitapide proves to be well tolerable in clinical practice. Strict guidance and adherence to diet restrictions are important to prevent or reduce possible side effects. Long term data regarding safety and reduction of cardiovascular events in comparison to lipoprotein-apheresis are to be determined.
EAS16-0641, DYSLIPIDEMIAS: DYSLIPIDEMIAS, SCREENING AND TREATMENT. ANALYSIS OF CANDIDATE SINGLE NUCLEOTIDE VARIATIONS ASSOCIATED WITH POLYGENIC HYPERCHOLESTEROLEMIA IN FAMILIES WITH THE CLINICAL DIAGNOSIS OF FAMILIAL HYPERCHOLESTEROLEMIA I. Lamiquiz Moneo 1, M.R. Perez-Ruiz 1, E. Jarauta 1, M.T. Tejedor 2, L. BailaRueda 3, A.M. Bea 3, R. Mateo-Gallego 3, A. Cenarro 3, F. Civeira 3. 1 Hospital n en Lípidos y Universitario Miguel Servet, Unidad Clínica de Investigacio Arteriosclerosis, zaragoza, Spain; 2 Universidad de zaragoza. Facultad de veterinaria, Departamento de Anatomía- Embriología y Gen etica Animal n Sanitaria Area de Genetica, Zaragoza, Spain; 3 Instituto de Investigacio n en Lípidos y Aragon IIS Aragon, Unidad Clínica de Investigacio Arteriosclerosis, zaragoza, Spain Introduction: Familial hypercholesterolemia (FH) is a common autosomal-dominant disorder caused by mutations in four known genes (LDLR, APOB, PCSK9 and APOE). However, about 20-40% of patients with the clinical diagnosis of heterozygous FH (heFH) are mutation-negative, probably due to the overlapping of heFH with severe forms of polygenic hypercholesterolemias (PH). Several single nucleotide variations (SNV) has been associated with PH. Objective: To establish the frequency of SNVs associated with PH in families with the clinical diagnosis of heFH, but without functional mutacions in candidates genes for FH in the proband. Methods: We selected 323 family members from 52 families with the clinical diagnosis of FH and without mutations in LDLR, APOB, PCSK9 and APOE in the proband. Genotyping of 5 PH associated SNVs were performed with TaqMan probes. For each individual, we calculated LDL cholesterolspecific gene scores using the weighted sum of the risk alleles. The weights used were the corresponding per-allele (risk) beta coefficients reported by the Global Lipid Genetic Consortium. Results: We observed that all SNVs, except APOB, showed differences with statistical significance (p<0.05) in allele frequencies when comparing with 1000 Genome Project, but without differences when comparing between affected and non-afected subjects within the families (Table). These 5 SNVs explained a small proportion (5.7%) of the variability in the LDL cholesterol.
Abstracts / Atherosclerosis 252 (2016) e1ee196
apheresis was started to selectively remove LDL-C from the plasma.LDL-C levels were measured prior to and after each procedure.C-IMT measurements were performed before the start of apheresis and approximately 1.5 year after performing apheresis. Results: Three HoFH patients were included.Their LDL-C levels before (and after) maximum statin therapy were 20.8 (13.3),16.9 (9.3),and 15.5 (11.2) mmol/L.All patients had extensive cutaneous xanthomas. The mean acute reductions in LDL-C after a single LDL-apheresis session were 77%,74% and 69%.The mean LDL-C levels during a stable period of on average 9 LDL-apheresis sessions were 4.1, 4.7 and 4.0 mmol/dL.Furthermore,a regression of cutaneous xanthomas was observed in all patients.In one patient, c-IMT decreased substantially (0.420 mm to 0.391 mm); c-IMT results for the other two patients did not differ significantly before and after starting LDL-apheresis.LDLapheresis was well tolerated; only mild side effects in 1 patient were reported. Conclusions: Our findings suggest that LDL-apheresis (DSA) in children with homozygous FH is a safe and effective method to lower LDL-C levels, decrease or stabilise c-IMT and to significantly reduce xanthoma size.
EAS16-0584, DYSLIPIDEMIAS: DYSLIPIDEMIAS, SCREENING AND TREATMENT. EVALUATION OF PLASMA-FED LIPID APHERESIS IN PATIENTS WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLAEMIA P. Downie 1, G. Bayly 1, L. Hart 2, S. Douglas 2, J. Griffin 2. 1 University Hospitals of Bristol NHS Foundation Trust, Department of Clinical BIochemistry, Bristol, United Kingdom; 2 University Hospitals of Bristol NHS Foundation Trust, Department of Haematology, Bristol, United Kingdom Objectives: In addition to diet and drug therapy LDL-apheresis is a treatment for Homozygous Familial Hypercholesterolaemia (HoFH). We investigated the use of a Medicollect column, fed plasma from a Terumo Spectra Optia through a Medicap Adasorb Machine to remove LDLcholesterol (LDL-C), in 2 patients with HoFH. Methods: Patient A (27), is a true homozygote, diagnosed with an LDL-C of 27mmol/L at the age of 3 and is treated with LDL-apheresis every two weeks. Patient B (34) is a compound heterozygote, diagnosed aged 11 with an LDL-C of 15mmol/L, currently treated with weekly LDL-apheresis. Previous LDL-apheresis was with Fresenius DALI. 8 procedures were performed for patient A, 12 for patient B. Results: In patient A, mean LDL-C reduction improved from 54 to 65% (p<0.0001) and from 61 to 71% (p<0.0001) in patient B. Subsequently in patient B, we investigated the use of the Fresnius ART universal machine using the Monet programme. 6 procedures were performed; mean LDL-C reduction improved from 61 to 74% (p < 0.0001). On average 15L of whole blood was processed by Monet as opposed to 10L for DALI. Conclusions: Initially there was no patient preference but towards the end of the 6 procedures our preferred Adasorb. The ART Universal machine is also unsuitable for patients with lower body weight due to the higher extra corporeal blood volume required (up to 885mls). However, advantages include its multiple programme selection, its similarity to DALI, its quiet operation, and the fact that it is a compact machine so easy to move/handle and store.
EAS16-0642, DYSLIPIDEMIAS: DYSLIPIDEMIAS, SCREENING AND TREATMENT. LOMITAPIDE IN HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA e FIRST EXPERIENCES IN CLINICAL PRACTICE A. Vogt. Medizinische KLinik 4, Stoffwechselambulanz, Muenchen, Germany Objectives: Lomitapide is a new class of drug to lower LDL-cholesterol (LDL-C) by inhibiting the microsomal transfer protein independently of
LDL-receptors. This might be a unique option for patients with homozygous familial hypercholesterolemia (hoFH). Methods: Four patients with proven hoFH undergoing regular lipoprotein-apheresis were started on Lomitapide in a clinical setting (named patient program). All patients were advised to reduce fat intact and to refrain from alcohol; concomitant medication and apheresis schedule were stable. Results: Two patients had no problems to follow diet instructions. One patient started exercising additionally and lost 20 kg. Pre apheresis LDL-C is reduced markedly. Patient 1: LDL-C -30% (5 mg), -50% (10 mg); patient 2: -47% (5 mg); patient 3: -24% (5 mg); patient 4: -30% (5 mg). In patient 1 apheresis frequency was reduced from every week to every two weeks. Dose increasing had to be delayed in two patients due to mild gastrointestinal symptoms. Liver enzymes increased in patient 1 due to alcohol intake and decreased with abstinence. Conclusions: Low dose Lomitapide reduced LDL-C markedly and treatment goals may be reached in the course of treatment for the first time in these patients with extreme LDL-C-levels. Necessity for lipoprotein-apheresis might be reduced. Lomitapide proves to be well tolerable in clinical practice. Strict guidance and adherence to diet restrictions are important to prevent or reduce possible side effects. Long term data regarding safety and reduction of cardiovascular events in comparison to lipoprotein-apheresis are to be determined.
EAS16-0641, DYSLIPIDEMIAS: DYSLIPIDEMIAS, SCREENING AND TREATMENT. ANALYSIS OF CANDIDATE SINGLE NUCLEOTIDE VARIATIONS ASSOCIATED WITH POLYGENIC HYPERCHOLESTEROLEMIA IN FAMILIES WITH THE CLINICAL DIAGNOSIS OF FAMILIAL HYPERCHOLESTEROLEMIA I. Lamiquiz Moneo 1, M.R. Perez-Ruiz 1, E. Jarauta 1, M.T. Tejedor 2, L. BailaRueda 3, A.M. Bea 3, R. Mateo-Gallego 3, A. Cenarro 3, F. Civeira 3. 1 Hospital n en Lípidos y Universitario Miguel Servet, Unidad Clínica de Investigacio Arteriosclerosis, zaragoza, Spain; 2 Universidad de zaragoza. Facultad de veterinaria, Departamento de Anatomía- Embriología y Gen etica Animal n Sanitaria Area de Genetica, Zaragoza, Spain; 3 Instituto de Investigacio n en Lípidos y Aragon IIS Aragon, Unidad Clínica de Investigacio Arteriosclerosis, zaragoza, Spain Introduction: Familial hypercholesterolemia (FH) is a common autosomal-dominant disorder caused by mutations in four known genes (LDLR, APOB, PCSK9 and APOE). However, about 20-40% of patients with the clinical diagnosis of heterozygous FH (heFH) are mutation-negative, probably due to the overlapping of heFH with severe forms of polygenic hypercholesterolemias (PH). Several single nucleotide variations (SNV) has been associated with PH. Objective: To establish the frequency of SNVs associated with PH in families with the clinical diagnosis of heFH, but without functional mutacions in candidates genes for FH in the proband. Methods: We selected 323 family members from 52 families with the clinical diagnosis of FH and without mutations in LDLR, APOB, PCSK9 and APOE in the proband. Genotyping of 5 PH associated SNVs were performed with TaqMan probes. For each individual, we calculated LDL cholesterolspecific gene scores using the weighted sum of the risk alleles. The weights used were the corresponding per-allele (risk) beta coefficients reported by the Global Lipid Genetic Consortium. Results: We observed that all SNVs, except APOB, showed differences with statistical significance (p<0.05) in allele frequencies when comparing with 1000 Genome Project, but without differences when comparing between affected and non-afected subjects within the families (Table). These 5 SNVs explained a small proportion (5.7%) of the variability in the LDL cholesterol.