Reduced incidence of cardiovascular events in hyper-Lp(a) patients on lipoprotein apheresis. The G.I.L.A. (Gruppo Interdisciplinare Aferesi Lipoproteica) pilot study.

BACKGROUND: Lipoprotein apheresis (LA) is the elective therapy for homozygous and other forms of Familial Hypercholesterolemia, Familial Combined Hypercholesterolemia, resistant/intolerant to lipid lowering drugs, and hyper-lipoproteinemia(a). Lipoprotein(a) [Lp(a)] has been classified as the most prevalent genetic risk factor for coronary artery disease and aortic valve stenosis. AIM: Our multicenter retrospective study has the aim to analyze the incidence of adverse cardiovascular events (ACVE) before and during the LA treatment, in subjects with elevated level of Lp(a) (>60 mg/dL) [hyper-Lp(a)] and chronic ischemic heart disease. METHODS: We collected data of 23 patients (mean age 63 ± 9 years, male 77%; from hospital of Pisa 11/23, Pistoia 7/23, Verona 2/23, Padova 2/23 and Ferrara 1/23), with hyper-Lp(a), pre-apheresis LDL-cholesterol <100 mg/dL, cardiovascular disease, on maximally tolerated lipid lowering therapy and LA treatment (median 7 years, interquartile range 3-9 years). The LA treatment was performed by heparin-induced LDL precipitation apheresis (16/23), dextran-sulphate (4/23), cascade filtration (2/23) and immunoadsorption (1/23). The time lapse between first cardiovascular event and beginning of apheresis was 6 years (interquartile range 1-12 years). RESULTS: The recorded ACVE, before and after the LA treatment inception, were 40 and 10 respectively (p < 0.05), notably, the AVCE rates/year were 0.43 and 0.11 respectively (p < 0.05) with a 74% reduction of event occurrence. CONCLUSIONS: Our data confirm long-term efficacy and positive impact of LA on morbidity in patients with hyper-Lp(a) and chronic ischemic heart disease on maximally tolerated lipid lowering therapy.

Detrimental effects of niacin/laropiprant on microvascular reactivity and red cell deformability in patients with elevated lipoprotein(a) levels.

Several studies have found a beneficial effect of nicotinic acid on lipid profile, but there remains a limitation in the clinical use of nicotinic acid due to its side effects. In this study, 46 (F/M = 22/24, age = 58.74 ± 10.02 years) patients with Lp(a) ≥500 mg/L and with a previous arterial thrombotic event were treated with nicotinic acid/laropiprant (Tredaptive®). We found a significant reduction in the Lp(a) values at T1 (after 12 months), with a decrease of 32.3 % from baseline levels. At T1, 11 patients (23.9 %) showed Lp(a) levels to be <500 mg/L. PAT values were significantly decreased after treatment (2.13 ± 0.81 vs 1.74 ± 0.42, p = 0.001), showing a worsening of endothelial function in 27 (58.6 %) patients. A significantly higher number of patients had RHI <1.5 after the treatment [18 (39.1 %) vs 8 (17.4 %)]. Blood rheology worsened as ED was impaired (p < 0.0001) after 12 months, whereas WHV, plasma viscosity, and red cell aggregation did not show any significant differences in comparison to baseline. Patients with a worsening in microvascular reactivity in comparison to baseline showed a marked impairment in ED (0.3327 ± 0.037 vs 0.3091 ± 0.0351; p < 0.0001), while others showed only a mild, even though significant, reduction (0.3347 ± 0.0299 vs 0.3272 ± 0.0235; p = 0.044). In the light of the results of HPS2-THRIVE study, we may hypothesize that the addition of laropiprant to niacin might be responsible for these negative effects. In turn, these effects might explain, at least in part, the lack of a clinical net benefit of niacin/laropiprant in the trial.

Therapeutic plasma exchange in patients with severe hypertriglyceridemia: a multicenter study.

Extremely high plasma triglyceride (TG) concentration is a recognized risk factor for acute pancreatitis (AP). In order to evaluate the therapeutic efficacy of plasma-exchange plasmapheresis in treating patients with severe hypertriglyceridemia (sHTG), 17 patients who had not responded to conventional medical therapy (fat-free diet plus pharmaceutical interventions) were referred for therapeutic plasma exchange (TPE) in a multicenter frame case series study. Two hundred seventeen TPE sessions were performed, and therapy is ongoing for five (30%) of the patients. After treatment, the mean plasma TG and total cholesterol concentrations were significantly reduced from 1929 and 510 mg/dL, to 762 and 227 mg/dL, respectively (P < or = 0.001 in both cases). In most cases, the interval between treatments was related to the clinical presentation and individual circumstances. The removal of TG-rich lipoproteins prevented relapses of AP. In this case series, TPE is confirmed as a safe and reliable method for treating patients with refractory sHTG when a severe complication, such as AP, is clinically demonstrated or can be actively prevented. Therefore, in cases where standard medical approaches fail to promote the clearance of TGs from plasma and a high risk of first or second hypertriglyceridemic pancreatitis persists, TPE provides a therapeutic option for preventing life-threatening sHTG.

Immunoadsorption apheresis and immunosuppressive drug therapy in the treatment of complicated HCV-related cryoglobulinemia.

The immunosuppressive drug therapy (IDT) is not always effective to avoid the development of complications in hepatitis C virus-related cryoglobulinemia (HCV-Cr). Removal of cryoglobulins by therapeutic plasmapheresis is currently accepted. In this randomized, parallel group study, 17 male and female patients aged 43-79 years, with complicated HCV-Cr, were submitted for 12 weeks (initial immunosuppressive therapy) to IDT (alpha-interferon, pegylated-interferon alpha-2a, cyclophosphamide, methylprednisolone, prednisone, cyclosporine, ribavirin, and melphalan). Then, they were randomly assigned to two parallel groups: A # 9 patients treated by immunoadsorption apheresis (Selesorb((R))) (IA) plus IDT, and B # 8 patients submitted to IDT only, for further 12 weeks. # 187 IA aphereses were performed. No adverse reactions or complications were observed. A Clinical Score (CS) was adapted from a pre-existing scoring model to evaluate signs and symptoms inherent to the underlying immunologic disorder. The CS was calculated at baseline (CS0), after the initial immunosuppressive therapy (CS1 = 12 weeks) when patients were treated only with IDT, and at the end of the study (24 weeks) in the group A (CSA; IA plus IDT) and B (CSB; IDT only). The score did not change significantly from CS0 to CS1. However, statistically significant differences were observed between CS1 and CSA (P < 0.001), and CSA versus CSB (P = 0.03), respectively. The changes observed were favorable to the patients assigned to the IA plus IDT group (A): in most case relief of symptoms and complications have been obtained.