Simulation of bempedoic acid and ezetimibe in the lipid-lowering treatment pathway in Austria using the contemporary SANTORINI cohort of high and very high risk patients.

OBJECTIVE: The low-density lipoprotein cholesterol goals in the 2019 European Society of Cardiology/European Atherosclerosis Society dyslipidaemia guidelines necessitate greater use of combination therapies. We describe a real-world cohort of patients in Austria and simulate the addition of oral bempedoic acid and ezetimibe to estimate the proportion of patients reaching goals. METHODS: Patients at high or very high cardiovascular risk on lipid-lowering treatments (excluding proprotein convertase subtilisin/kexin type 9 inhibitors) from the Austrian cohort of the observational SANTORINI study were included using specific criteria. For patients not at their risk-based goals at baseline, addition of ezetimibe (if not already received) and subsequently bempedoic acid was simulated using a Monte Carlo simulation. RESULTS: A cohort of patients (N = 144) with a mean low-density lipoprotein cholesterol of 76.4 mg/dL, with 94% (n = 135) on statins and 24% (n = 35) on ezetimibe monotherapy or in combination, were used in the simulation. Only 36% of patients were at goal (n = 52). Sequential simulation of ezetimibe (where applicable) and bempedoic acid increased the proportion of patients at goal to 69% (n = 100), with a decrease in the mean low-density lipoprotein cholesterol from 76.4 mg/dL at baseline to 57.7 mg/dL overall. CONCLUSIONS: The SANTORINI real-world data in Austria suggest that a proportion of high and very high-risk patients remain below the guideline-recommended low-density lipoprotein cholesterol goals. Optimising use of oral ezetimibe and bempedoic acid after statins in the lipid-lowering pathway could result in substantially more patients attaining low-density lipoprotein cholesterol goals, likely with additional health benefits.

Blood flow characteristics in the ascending aorta after TAVI compared to surgical aortic valve replacement.

Ascending aortic blood flow characteristics are altered after aortic valve surgery, but the effect of transcatheter aortic valve implantation (TAVI) is unknown. Abnormal flow may be associated with aortic and cardiac remodeling. We analyzed blood flow characteristics in the ascending aorta after TAVI in comparison to conventional stented aortic bioprostheses (AVR) and healthy subjects using time-resolved three-dimensional flow-sensitive cardiovascular magnetic resonance imaging (4D-flow MRI). Seventeen patients with TAVI (Edwards Sapien XT), 12 with AVR and 9 healthy controls underwent 4D-flow MRI of the ascending aorta. Target parameters were: severity of vortical and helical flow pattern (semiquantitative grading from 0 = none to 3 = severe) and the local distribution of systolic wall shear stress (WSSsystole). AVR revealed significantly more extensive vortical and helical flow pattern than TAVI (p = 0.042 and p = 0.002) and controls (p < 0.001 and p = 0.001). TAVI showed significantly more extensive vortical flow than controls (p < 0.001). Both TAVI and AVR revealed marked blood flow eccentricity (64.7 and 66.7%, respectively), whereas controls showed central blood flow (88.9%). TAVI and AVR exhibited an asymmetric distribution of WSSsystole in the mid-ascending aorta with local maxima at the right anterior aortic wall and local minima at the left posterior wall. In contrast, controls showed a symmetric distribution of WSSsystole along the aortic circumference. Blood flow was significantly altered in the ascending aorta after TAVI and AVR. Changes were similar regarding WSSsystole distribution, while TAVI resulted in less helical and vortical blood flow.

Therapeutic potential of mipomersen in the management of familial hypercholesterolaemia.

High levels of low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) [Lp(a)] are associated with early morbidity and mortality caused by cardiovascular disease (CVD). There are hints that a reduction of LDL-C levels beyond currently advocated targets, and the use of drugs that also have Lp(a)-lowering potential, could provide further clinical benefit. Today, LDL apheresis is the only available treatment option to achieve further lowering of apolipoprotein-B (apo-B)-containing lipoproteins, especially Lp(a). Mipomersen is currently being studied in patients with mild to severe hypercholesterolaemia as add-on therapy to other lipid-lowering therapy, as monotherapy in patients who are intolerant of HMG-CoA reductase inhibitors (statins) and who are at high risk for CVD. Patients affected by homozygous or heterozygous familial hypercholesterolaemia (FH), which are inherited autosomal co-dominant disorders characterized by a marked elevation of serum LDL-C concentration, remain a clinical challenge, especially when their CVD risk is aggravated by additionally elevated Lp(a) levels. Mipomersen is a 20-mer oligonucleotide [2'-O-(2-methoxy) ethyl-modified oligonucleotide], a second-generation antisense oligonucleotide (AOS), complementary to the coding region for human-specific apo-B-100 messenger RNA (mRNA). Mipomersen inhibits apo-B-100 synthesis and is consequently a new treatment strategy to lower apo-B-containing lipoproteins like LDL-C and Lp(a) in patients at high risk for CVD not on target or intolerant to statins. This article focuses on mipomersen and gives an overview of the current status of mipomersen as a promising treatment option. Recent studies have shown a decrease in LDL-C levels of 22-42.2% and in Lp(a) of 19.6-31.1% from baseline, depending on study design. Dose-dependent reductions of very low-density lipoprotein cholesterol (VLDL-C) and triglyceride levels have also been observed. Although the short-term efficacy and safety of mipomersen have been proven, side effects like injection-site reactions (up to 90-100%), increased liver enzymes, cephalgias, nasopharyngitis, myalgia, nausea and fatigue must be mentioned and critically discussed. Furthermore, we need more data on the long-term side effects, especially regarding the long-term potential for hepatic steatosis. Data on cardiovascular outcomes with mipomersen are also not yet available.

[Adipokine update - new molecules, new functions]. / Adipokine update - neue Moleküle, neue Funktionen.

The prevalence of obesity is rising worldwide. Recent research findings show that adipose tissue is a highly active endocrine organ, which is involved in many physiological processes. These metabolic processes are influenced by products of the adipose tissue, so-called adipokines, which play a crucial role in the pathogenesis of the metabolic syndrome and cardiovascular disease. In addition, the two major fat depots - intraabdominal and subcutaneous - differ in their ability to secrete adipokines. In recent years the importance of the association between intraabdominal fat and the development of insulin resistance, diabetes mellitus type 2 and dyslipidemia was recognized. Therefore, accumulation of visceral adipose tissue contributes due to its ability to secrete a different pattern of adipokines to increased morbidity and mortality. This review aims to characterize novel, newly recognized adipokines and to discuss their roles in the pathogenesis of insulin resistance and atherosclerosis, as well as other metabolic complications.