Efficacy, safety, and tolerability of long-term lipoprotein apheresis in patients with LDL- or Lp(a) hyperlipoproteinemia: Findings gathered from more than 36,000 treatments at one center in Germany.

LDL cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) are main risk factors for cardiovascular disease (CVD). Efficacy, safety, and tolerability of lipoprotein apheresis (LA) were investigated in 36,745 LA treatments of 118 patients with CVD in a retrospective, monocentric study. Indications were severe hypercholesterolemia (n = 83) or isolated Lp(a) hyperlipoproteinemia (n = 35). Average age of patients at start of LA treatment was 58.1 years for males and 62.5 years for females. Medium interval between the first cardiovascular event and LA treatment was 6.4 ± 5.6 years and the average LA treatment period was 6.8 ± 4.9 years. On average treatments were performed once a week, via peripheral venous access in 79.3% of non-hemodialysis patients. In patients with hypercholesterolemia initial pre-LA LDL-C was lowered from 176.4 ± 67.0 mg/dL by 66.7 ± 10.8% per session, achieving a long-term interval mean value of 119.8 ± 34.7 mg/dL, i.e. reduction by 32.1 ± 19.6% (p < 0.0001). In patients with isolated elevated Lp(a) initial pre-LA Lp(a) was lowered from 127.2 ± 67.3 mg/dL by 66.8 ± 5.8% per session, achieving a long-term interval mean value of 60.0 ± 19.5 mg/dL, i.e. reduction by 52.8 ± 23.0% (p < 0.0001). After start of LA the average annual rate of major adverse coronary events (MACE) of all patients declined by 79.7% (p < 0.0001). Subgroup analysis showed decline by 73.7% (p < 0.0001) in patients with severe hypercholesterolemia, and by 90.4% (p < 0.0001) in patients with isolated elevated Lp(a). Adverse events (AE) occurred in 1.1% of treatments. LA treatment of patients with high risk for CVD due to LDL and/or Lp(a) hyperlipoproteinemia was effective, safe, and well tolerated. The number of cardiovascular events, at least during a six-year period, declined by 80%.

Clinical benefit of long-term lipoprotein apheresis in patients with severe hypercholesterolemia or Lp(a)-hyperlipoproteinemia with progressive cardiovascular disease.

Low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) are established causal risk factors for cardiovascular disease (CVD). Efficacy, safety, and tolerability of lipoprotein apheresis (LA) were investigated in 118 patients with CVD covering a period with 36,745 LA treatments in a retrospective, monocentric study. Indications for LA were severe hypercholesterolemia (n = 83) or isolated Lp(a) hyperlipoproteinemia (Lp(a)-HLP) (n = 35). In patients with hypercholesterolemia, initial pre-LA LDL-C was 176.4 ± 67.0 mg/dL. In patients with isolated Lp(a)-HLP, initial pre-LA Lp(a) was 127.2 ± 67.3 mg/dL. Mean reduction rates of LA were 67 % for both LDL-C and Lp(a). During chronic LA, the average annual rate of major adverse cardiac events of all patients declined by 79.7 % (p < 0.0001). Subgroup analysis showed decline by 73.7 % (p < 0.0001) in patients with severe hypercholesterolemia, and by 90.4 % (p < 0.0001) in patients with isolated Lp(a)-HLP. Adverse events occurred in 1.1 % of treatments. LA treatment of patients with a high risk for CVD due to hypercholesterolemia and/or Lp(a)-HLP demonstrated clinical benefit and was safe and well tolerated.

Changes in acid-base, electrolyte and hemoglobin concentrations during infusion of hydroxyethyl starch 130/0.42/6 : 1 in normal saline or in balanced electrolyte solution in children.

INTRODUCTION: A balanced volume replacement strategy is a well established concept for correcting hypovolemia using plasma adapted isotonic crystalloid solutions with a physiological electrolyte pattern and acetate as bicarbonate precursor. Recently, third-generation hydroxyethyl starch (HES) has also become available in a balanced electrolyte solution instead of normal saline. Therefore, in this prospective non-interventional clinical study, the perioperative administration of HES 130/0.42/6 : 1 in normal saline (ns-HES) and in balanced electrolyte solution (bal-HES) was evaluated in children with a focus on acid-base, electrolyte and hemoglobin changes. METHODS: Following local ethics committee approval, pediatric patients aged up to 12 years with an ASA risk score of I-III undergoing perioperative administration of HES (ns-HES from May 2006 to December 2007, bal-HES from January 2008 to January 2009) were included. Patient demographics, the performed procedure, adverse drug reactions, hemodynamic data and the results of blood gas analysis were documented with a focus on changes in acid-base, electrolyte and hemoglobin concentrations. RESULTS: Of 396 enrolled patients (ASA I-III; age 2.3 +/- 3, range day of birth - 12 years; body weight 10.8 +/- 9, range 0.9-52 kg), 249 received ns-HES and 147 bal-HES (mean volume infused 9.9 +/- 4 and 9.4 +/- 6.9 ml x kg(-1), respectively). After HES infusion, hemoglobin decreased in both groups, whereas bicarbonate and base excess (BE) decreased only with ns-HES and remained stable with bal-HES (BE before infusion: ns-HES -1.8 +/- 2.8, bal-HES -1.7 +/- 2.7 mmol x l(-1); after infusion: ns-HES -2.6 +/- 2.4; bal-HES -1.6 +/- 2.6 mmol x l(-1), P < 0.05). Chloride (Cl) concentrations increased in both groups and were significantly higher with ns-HES (Cl before infusion: ns-HES 105.6 +/- 3.7, bal-HES 105.1 +/- 2.8 mmol x l(-1); after infusion: ns-HES 107.7 +/- 3.2, bal-HES 106.3 +/- 2.9 mmol x l(-1), P < 0.01). No serious adverse drug reactions were observed. CONCLUSION: Infusion related iatrogenic acid-base and electrolyte alterations can be minimized by using hydroxyethyl starch in a balanced electrolyte solution instead of normal saline.

Hydroxyethyl starch 130/0.42/6:1 for perioperative plasma volume replacement in children: preliminary results of a European Prospective Multicenter Observational Postauthorization Safety Study (PASS).

BACKGROUND: Several clinical studies have shown that hydroxyethyl starch (HES) may be as effective and safe as, but less expensive than, albumin when used for perioperative plasma volume replacement (PVR) in children. The new third generation HES 130/0.42 solution was designed to reduce adverse drug reactions (ADRs) and improve safety while maintaining efficacy. Therefore, the objective of this prospective multicenter observational postauthorization safety study (PASS) was to evaluate the perioperative use of HES 130/0.42 in 1000 children with a particular focus on possible ADRs. METHODS: Approximately 300 of 1000 pediatric patients aged up to 12 years with ASA risk scores of I-III receiving perioperative HES 130/0.42 (Venofundin 6%; Braun, Melsungen, Germany) should be enrolled for interims analysis in the first year. The statistical sample size calculation showed that this number of patients would be sufficient to detect a 1% incidence of ADRs. Following approval by local ethics committee, patient demographics, data relating to HES 130/0.42 use, the procedures performed, anesthesia, and ADRs were documented with a particular focus on cardiovascular stability, hemodilution, acid-base balance, renal function, blood coagulation, and hypersensitivity. RESULTS: Three hundred and sixteen children (ASA I-III, age 3 +/- 3.4 [range, day of birth-12 years], body weight 13 +/- 10.5 [range, 1.1-60 kg]) were studied at five centers in Germany, Austria, and Italy from May 2006 until August 2007. Forty-five percent of the patients underwent abdominal surgery, 12.4% urologic procedures, 11.4% thoracic surgery, 7.6% orthopedic procedures, and 7% cardiovascular surgery. The mean volume of infused HES 130/0.42 was 11 +/- 4.8 ml x kg(-1) (range, 5-42). Cardiovascular stability was maintained in all cases. After HES infusion, hemoglobin (11.5 vs 10.25 g x dl(-1)), base excess (-2 vs -2.7 mmol x l(-1)), anion gap (12.9 vs 11.2 mmol x l(-1)), and strong ion difference (34.3 vs 31.4 mmol x L(-1)) decreased, and chloride (105.7 vs 107.8 mmol x l(-1)) increased significantly (P < 0.05). No serious ADRs (i.e., anaphylactoid reaction, renal failure, clotting disorders) were observed. CONCLUSION: Moderate doses of HES 130/0.42 help to maintain cardiovascular stability and lead to only moderate changes in hemoglobin concentration and acid-base balance in children. The probability of serious ADRs is lower than 1%. Therefore, HES 130/0.42 for PVR seems to be safe and effective even in neonates and small infants with normal renal function and coagulation.