Chairs: B. Jäger (Mühlheim a.d. Ruhr, Germany), H. Sinzinger (Vienna, Austria)
|Worsening of angina after stopping apheresis treatment in a patient with raised lipoprotein (a)
1 Royal Brompton & Harefield NHS Foundation Trust, Harefield Hospital, Cardiology, Harefield, Middlesex, United Kingdom
Abstract text :
In 2002 a 42 year old man presented with unstable angina. His only known risk factor was type IIb hyperlipidaemia. Cardiac investigations revealed significant triple vessel coronary artery disease. He initially had PCI and stent deployment and in 2004 due to worsening of symptoms and progression of the disease he underwent surgical revascularisation. Initially he symptomatically improved however, he had a recurrence of unstable angina and required coronary stent insertion every 4-6 weeks amounting to a total of 12 stents. In 2007 he was referred to the Lipid Clinic and his lipoprotein(a) (Lp(a)) was 1200mg/L, LDL 1.3mmol/L, HDL 108mmol/L, TG 1.4mmol/L. Lipid lowering medication included Rosuvastatin 40mg, Bezafibrate 400mg, Ezetimibe 10mg and Omacor 1g od.
Lipoprotein apheresis was commenced in August 2007 initially using the Kaneka whole blood DX21 system and from July 2014, the double filtration system. Treatment was carried out on a 2 weekly basis until August 2017 when the patient moved to Bermuda.
Lipoprotein apheresis treatment resulted in an average acute reduction of 63.7% in Lp(a) and an average interval mean reduction of 31.33% (see table).
Since commencing apheresis treatment his functional status improved with significant improvement in angina and he was able to work full-time. Lipoprotein apheresis also slowed the progression of his coronary disease. Since commencement of treatment he has required nine percutaneous interventions to the RCA. Apheresis treatment was not available in Bermuda and in November 2017 he noticed a recurrence of worsening angina which adversely affected his quality of life.
Raised Lp(a) is an independent risk factor for CAD. Since commencement of lipoprotein apheresis there has been a significant reduction in his Lp(a) which has correlated in improvement in symptoms and quality of life.
|Proprotein convertase subtilisin/ kexine type 9 inhibitors (PCSK9i) in patients with indications for lipoprotein apheresis (LA)
1 University Hospital and Faculty of Medicine Carl Gustav Carus, Lipidology, Department of Internal Medicine III, Dresden, Germany
Abstract text :
LA is the last-resort therapeutic option for patients with highly elevated atherogenic lipoproteins levels. Facing the introduction of the PCSK9i, we analyzed to which extent they might replace LA.
The medical records of 152 persons having an indication for LA were reviewed with respect to efficacy and safety of PCSK9i. On the other side we analyzed the data of 37 LA patients, taking PCSK9i additionally to the extracorporeal treatment
The mean reduction of LDL-Cholesterol (LDL-C) after 4 months of PCSK9i administration was 53.03%. In 51 (34%) patients the target value could not be reached. 69 (45%) persons suffered from adverse effects: influenza symptoms (23), muscle and joint pains (22), local skin reactions (7), collapse (8) and exanthema (6). In 27 subjects the adverse effects were long-term. Because of the adverse effects the PCSK9i medication was switched (from alirocumab to evolocumab or vice versa) in 7 and completely terminated in 12 (8%) patients. 8 (22%) of 37 LA patients, taking PCSK9i, could stop LA. 29 persons continued the extracorporeal treatment because of PCSK9i termination, insufficient LDL-C reduction at PCSK9i or/and additionally elevated lipoprotein (a). In 6 persons the intervals between two sessions could be extended from 1 to 2 or from 2 to 4 weeks.
The efficacy and safety of PCSK9i in a real clinical setting are in clear contrast to study data. Only 22% from patients with highly elevated LDL-C could stop LA after having been switched to PCSK9i. These data overturn some speculations about the future perspective of LA therapy.
|Response of lipoprotein(a) levels to PCSK9 inhibitors: The Tuscany Reference Center for hereditary dyslipidemia experience
1 Fondazione Toscana "Gabriele Monasterio", U.O. Lipoaferesi, Pisa, Italy
Abstract text :
Purpose. Lipoprotein (a) [Lp(a)] has been classified as the single most prevalent genetic risk factor for coronary artery disease and aortic valve stenosis. Clinical trials with proprotein convertase subtilisin/kexin type 9 monoclonal antibody inhibitors (PCSK9i) reported a significant Lp(a)-lowering effect.
Methods. We enrolled 21 patients (mean age 61±8 years, male 67%) affected by hyper-Lp(a) (defined as >50 mg/dl), familial hypercholesterolemia (FH) complicated by coronary heart disease assigned to PCSK9i. No relevant comorbidities were present in any patients.
PCSK9i (evolocumab 140 mg in 14 subjects, alirocumab 150 mg in 5 subjects or alirocumab 75 mg in 2 subjects) were administered, every 2 weeks, on top of background lipid-lowering-therapy. Furthermore, 10/21 patients were chronically on LDL Apheresis (LA) treatment. Selective LA procedures were performed with 14 days inter-apheretic interval treating 1.5 patient plasma volume for session. In subjects on LA, PCSK9i were administered at the end of apheresis procedure.
Results. During the 6 months study period, 1/21 patient on LA had been droped-out because of severe myalgia. Other adverse events were reported in 5/20 of patients: 3/5 showed low grade of myalgia that required a lipid-lowering down-grade, 2/5 patients presented visual impairment and were scheduled for cataract surgery.
The cumulative effect of lipid lowering treatment on the all group of patients studied showed a 32% decrease in total cholesterol (p<0.001), 49% in LDL-c (p<0.001) and 15% in Lp(a) median levels (p<0.001).
The subgroup of LA patients on PCSK9i (9/20) showed reduction of 34% (p<0.001) in total cholesterol, 53% (p<0.001) in LDL-c and 17% (p<0.01) in Lp(a) median levels, while subgroup on PCSK9i (11/20) showed a decrease in total cholesterol of 28% (p<0.01), 46% in LDL-c (p<0.01) and 22% (p<0.05) in Lp(a) median levels.
Hyper-Lp(a), especially when associated to FH, is a clinical condition that requires the highest personalization in lipid-lowering therapy. While LA represents a definite treatment to lower Lp(a) and cardiovascular events, PCSK9i would be a supplementary opportunity for treatment hyper-Lp(a) patients. Our data are in disagreement with clinical trials showing a 30% decrease in Lp(a).
|Hyperlipoproteinemia (a) in four Pediatric Patients with Cerebral Insult
1 Medical University of Vienna, Department of Pediatric and Adolescent Medicine, Division of Pediatric Pulmonology, Allergology and Endocrinology, 1090 , Austria
Abstract text :
Lipoprotein (a) (Lp(a)) is a major risk factor for cerebrovascular diseases, especially for stroke. Data about lipoprotein (a) and stroke in the pediatric and adolescent population is scarce, and guidelines for the management of those patients are missing. The aim of the report is to describe clinical and biochemical findings in children and adolescents with stroke and hyperlipoproteinemia (a).
We report data of four patients (median age at diagnosis 11.5 years; range: 6-17 years) with stroke and hyperlipoproteinema (a), who presented in our clinic between 2012 and 2017. Diagnosis was based on MRI (magnetic resonance imaging) findings. Other diseases like hypercoagulable states, autoimmune disorders, infections, heart diseases, hypertension, elevated homocysteine etc. were excluded in all patients. Further, all patients received a low fat diet, lipid lowering medication (statins) and as anticoagulation treatment low dose acetylsalicylic acid. The patients get regular clinical checks with neurological examination, lipoprotein profile and cardiovascular evaluation (ECG), echocardiography, intima media thickness (IMT) of supraaortic arteries.
Presenting symptoms were headache (n=2), hemiparesthesia (n=2), homonymous hemianopia (n=2) and muscular hypotonia (n=1). MRI showed lesions in the putamen, in the temporoccipital lobe and occipital lobe as well as in the capsula interna and thalamic region.
Initial Lp (a) was 166.5 mg/dl (=median, range: 106-236 mg/dl) and initial LDL-cholesterol (LDL-C) was 114.6 mg/dl (=median, range: 77.8-114.6 mg/dl). All patients reached LDL-C levels <70 mg/dl under oral medication. Furthermore, IMT of supraaortic arteries and cardiac evaluation were normal in all patients. None of the patients had a further stroke event over a median observation period of 1.75 years (range: 0.25-5 years) and in all of them neurological deficits diminished.
Lipoprotein (a) is an important risk factor for stroke, also in pediatric and adolescents patients. The treatment with anticoagulation, lipid lowering medication and healthy lifestyle should eliminate further cardiovascular risk factors, especially in a young population.
|Short- and long-term effects of lipoprotein apheresis on plasma levels of ACTH, adrenal hormones and renin in patients with therapy-resistant dyslipidemia
1 University Hospital at the Technische Universität Dresden, Department of Internal Medicine III, Dresden, Germany
Abstract text :
Purpose: Lipoprotein apheresis (LA) is a highly effective method to improve clinical and metabolic situation in patients with therapy-resistant disorders of lipid metabolism. Whether repeated massive reduction of LDL-cholesterol may interfere with steroid hormone synthesis, which could become clinically relevant, is unknown so far. Thus, the aim of this study was to identify possible short- and long-term effects of LA by determination of plasma levels of ACTH, cortisol, aldosterone, DHEAS, and renin.
Methods: In total, 41 patients, treated with one of these four LA techniques were studied: 1. Lipid Filtration (LF; n=8), 2. Dextran Sulfate Adsorption (DSA; n=10), 3. Membrane Filtration Optimised Novel Extracorporeal Treatment (MONET; n=8), and 4. Direct Absorption of Lipoproteins (DALI; n=15). Hormone levels were analyzed before and after five LA sessions with an interval of 20 weeks covering a total observation time of two years. In addition patients were comprehensively characterized by clinical and laboratory data.
Results: Acute effects of LA were characterized by significant reductions of ACTH and cortisol during LA with DSA, MONET, and DALI, but not with LF. A decrease of aldosterone could be observed in LA with LF and MONET. DHEAS and renin remained unchanged during all LA methods. Rebound effects three days after LA resulted in restored pre-apheresis values in ACTH, cortisol, and aldosterone (LF, MONET, DALI) or even significantly higher values in comparison to pre-apheresis values (ACTH and cortisol in DSA).
Analysis of long-term fluctuations of plasma hormone levels did not reveal any significant changes in pre- or post-apheresis values for any of the LA procedures.
Conclusion: In conclusion, these data suggest that although different LA techniques considerably differ in their acute effects on steroid hormone levels during LA, they did not alter long-term hormone levels sustainably.