H.E.L.P. LDL-apheresis clinical experience in Italy 1 H.E.L.P. LDL-apheresis clinical experience in Italy Stefanutti C, Di Giacomo S, Shafii M, Morozzi C, Mazzilli S, and the Italian Multicenter Study (IMS) LDL-apheresis (LDLa) Working Group ISFA Vienna 2011 8th International Society for Apheresis Congress September 14th – 17th University Hospital, Vienna - Austria Lake of Bracciano, NW Rome, September 2011

2 Background and aims The clinical benefits of LDL-apheresis (LDL-A) have been demonstrated in: the H.E.L.P. LDL-A Multicenter Study the LDL-A Atherosclerosis Regression Study (LAARS) the German Multicenter LDL-A Trial the FH Regression Study. The efficacy and safety of the heparin-induced extra-corporeal LDL-precipitation (H.E.L.P.®) LDL–A on long-term, has been studied in a single center (Rome, “La Sapienza” University) open retrospective survey. Furthermore, the increasing use of H.E.L.P. LDL-A in Italy was recently reported also by the coordination (Rome) of the Italian Multicenter Study on LDL-apheresis Working Group (unpublished data).

The data from 22 (♂ 13 - ♀ 9) patients were evaluated accounting for 1437 H.E.L.P. LDL-A sessions. The Plasmat™ Futura System is used selectively to remove apoprotein B100-containing- lipoproteins in patients with severe dyslipidemia in our center. Regular treatment with H.E.L.P. LDL-A was administered weekly or biweekly in Hoz and Htz FH patients. Vascular accesses: antecubital veins Plasma volume treated per session: 3000 ml 3 Patients and Methods

Patients Age Dyslipidemia CAD and/or AVD Activity parameters 22 ♂: 13 ♀: 9 Age X: 32.7 SD: 15.4 Dyslipidemia Homozygous-Compound FH: 10 Heterozygous FH: 12 CAD and/or AVD 77.2 %(documented by angiography) Activity parameters Homozygous FH mg/dL X SD Heterozygous FH X SD LDL-Chol before after 402 148 85 34 388 138 56 20 HDL-Chol 50 41 7 8 45 36 6 Lp(a) 19 3 31 12 14 Fibrinogen 224 80 54 21 315 134 46 32 4 4 4

SASSARI OZIERI NUORO CAGLIARI PALERMO BARI L’AQUILA ROMA PISTOIA REGGIO EMILIA GALLARATE MILANO PADOVA TRIESTE VERONA VITERBO PRATO FORLÌ 5 Coordinating centre Italian Multicenter Study on LDL-apheresis Working Group (# 23 Centers) 5

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Total patients under treatment in Italy: # 211 8 IMSLDLa-WG: # 157 Not belonging: # 54 Total patients under treatment in Italy: # 211

27 62 IMS LDLa 2011 (2009 activity; # 18 Centers; # 101 patients) MPVT MBVT MPVS 3127 ± 518.5 (1700 vs 4000 ml) 8666.6 ± 1384.4 (5000 vs 10000 ml) 3500 ± 300 (3200 vs 3800 ml) Major side effects (# total events) Minor side effects (# total events) 27 62 IMSLDLa-WP:# 101 Patients under treatment (2009)

Symptomatic Hypocalcemia 8 Hematoma by venipuncture 230 10 Italian Multicenter Study on Low-Density Lipoprotein Apheresis (IMS-LDLa): Side effects and number of events (2007) IMS-LDLa Centers = 18 Side effects No. of events Symptomatic Hypocalcemia 8 Hematoma by venipuncture 230 Low outlet flow 125 Circuit coagulation 44 Allergic reaction 19 Gastrointestinal discomfort/vomiting 19 Fever and shivers 0 Hypotension/collapse 11 Vasovagal reaction 13 Hemolysis 6 Cardiac arrhythmias 0 Stefanutti C and the Italian Multicenter Study (IMS) on LDL-apheresis (LDLa) Working Group (2010): The Italian Multicenter Study on LDL-apheresis: retrospective analysis (2007) Ther Apher Dial. 14(1):79-86.

IMSLDLa-WG Survey 2009, unpublished 11 IMSLDLa-WG Survey 2009, unpublished

IMSLDLa-WG Survey 2009, unpublished 12 IMSLDLa-WG Survey 2009, unpublished

IMSLDLa-WG Survey 2009, unpublished 13 IMSLDLa-WG Survey 2009, unpublished

Results and Discussion 14 Results and Discussion The 2nd survey of the IMSLDLa-WG was carried out. The study involved 18 centres for LDL-A. The patients enrolled in 2009 were 101 (66 males; 35 females) aged 47 ± 18 years. The average age for initial drug treatment before LDL-A was 31 ± 18 years. The mean age to the 1st LDL-A was 37 ± 20 years. The average duration of treatment was 9 ± 6 years. The techniques utilized were: HELP, DALI, DSC, PEX, CF. The mean treated plasma and blood volumes/session were 3127 ± 518 mL and 8666 ± 1384 mL, respectively. The average plasma volume substituted was 3500 ± 300 mL. The hypolipidemic drugs given before LDL-A were: ezetimibe+simvastatin, atorvastatin, rosuvastatin, ω-3 fatty acids, and fenofibrate.

15 Conclusion Interestingly, ischemic events were not observed in patients with CAD, and without CAD treated with all LDL-A and LA techniques because of refractoriness or intolerance to drugs, over 9 ± 6 years treatment. H.E.L.P. LDL-A treatment was beneficial and safe in patients with refractory hypercholesterolemia genetically determined, CAD. The increasing use of H.E.L.P. LDL-A in Italy was recently reported also by the coordination (Rome) of the Italian Multicenter Study on LDL-apheresis Working Group (unpublished data). Among 101 patients submitted to LDL-A in 18 Italian centers, 41 have been treated with H.E.L.P. LDL-A.

16 Take-home message The Italian Multicenter Study on LDL-apheresis Working Group This group is the organizational and operative forum where experts in LDL-A and LA in our country collaborate on clinical, technical, scientific and experimental themes. Concerning the guidelines, the group has decided to develop a common protocol of orientation, also specialized in updating and training, that could be extended to new centers that desire to join the network. The II Italian Consensus Conference on LDL-apheresis (2009) was made possible by the collaborating centers belonging to the above mentioned group. Stefanutti C (2010): The 2009 2nd Italian Consensus Conference on LDL-apheresis Nutrition, Metabolism & Cardiovascular Diseases. 20(10) 761-762

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