New Therapies for Primary Hyperlipidaemia

Primary hyperlipidemias include a heterogeneous set of monogenic and polygenic conditions characterized by a strong family aggregation, severe forms of hypercholesterolemia and/or hypertriglyceridemia, appearance early on life and a high risk of cardiovascular events and/or recurrent pancreatitis. In real life, a small proportion of the primary hyperlipidemia cases is recognized and treated properly. Our goal is to present an update of current and upcoming therapies for patients with primary hyperlipidemia. Recently, new lipid lowering medications have obtained FDA and/or EMA authorization. These drugs target metabolic pathways, including (ATP)-citrate lyase (bempedoic acid), PCSK9 (inclisiran), apo CIII (volanesorsen) and ANGPTL3 (volanesorsen), that have additive effects with the actions of the currently available therapies (i.e. statins, ezetimibe or fibrates). We discuss the potential clinical indications for the novel medications. To conclude, the addition of these new medications to the therapeutic options for primary hyperlipidemia patients may increase the likelihood to achieve the treatment targets. Also, it could be a safer alternative for subjects with side effects for the currently available drugs.

Reactive Seizures Due to Hyperlipidemia in a Maltese Dog

Background: Primary hyperlipidemia is a condition that affects some specific breeds. It has been previously described in Miniature Shnauzer, Beagles, Shetland Shepdog and West Highland White Terrier. There are no reports of primary hyperlipidemia in Maltese dogs. It is a hereditary disorder of lipoprotein metabolism. The etiology is unknown and may be related to a genetic problem in lipoprotein lipase or to the absence of apaprotein CII. Clinical signs include spontaneous arterosclerosis, retinal lipemia, cutaneous xanthomas, abdominal pain, lethargy, vomiting and / or diarrhea. Neurological manifestations such as seizures and behavioral changes may also occur. The aim of this report is to describe a case of reactive seizures due to hyperlipidemia in a dog.Case: A 5-year-old male Maltese dog was admitted with a history of seizures. Hypertension and abdominal distension with large amounts of intestinal gases were found in general physical examination. Neurological examination revealed impaired nasal septum sensory perception, which was slightly bilaterally reduced, and pain on cervical palpation and in the brachial plexus region. Based on history and clinical examination, it was possible to locate the lesion in the thalamocortical region and to suspect idiopathic epilepsy, reactive seizures, and symptomatic epilepsy due to meningoencephalitis of unknown origin. The diagnosis of primary hyperlipidemia was made by exclusion with the aid of laboratory tests and ultrasound. After the establishment of a fat restriction diet, bezafibrate, phenobarbital, and omega-3 supplementation, the animal improved significantly with the reduction of epileptic seizures.Discussion: The initial clinical suspicion was hyperadrenocorticism as the primary cause of hyperlipidemia. This suspicion was based on the presence of polyphagia, polydipsia, polyuria and abdominal distension, together with laboratory results of thrombocytosis, increased ALT and AF, and hyposenuria; but ultrasound images and ACTH stimulation test ruled out this differential diagnosis. Hypothyroidism was also ruled out since LDL values were normal and the animal was extremely active. Regarding nephrotic syndrome, it was also excluded for some alterations would be present, such as severe proteinuria, cholesterol reduction and hypoalbuminemia. As for diabetes mellitus, it was discarded because of the dog’s young age and due to the absence of suggestive clinical signs. The suspicion of primary hyperlipidemia was based on increased levels of triglycerides, and the presumptive diagnosis was of reactive seizures due to hyperlipidemia. It is essential, when treating hyperlipidemia, to readjust to a low-calorie diet with fat concentration below 8% and protein level above 18%. Generally, these restricted diets are for life. Omega-3 supplementation can be performed to help maintain low levels of triglycerides. Drug therapy is usually carried out with bezafibrate, which is used in human medicine as treatment for hypertriglyceridemia, and has showed good results in the control of hypertriglyceridemia and hypercholesterolemia in dogs with primary and secondary hyperlipidemia. Six months after the beginning of the treatment, the animal no longer presented abdominal distension and pain, cholesterol values and its fractions were controlled, as well as triglycerides. Seizures were also under control. Therefore, hyperlipidemia is an important differential diagnosis in cases of patients presenting seizures, especially when dealing with young animals showing signs of metabolic diseases.

YLTZ in the treatment of primary hyperlipidemia (phlegm-turbid obstruction type): study protocol for randomized, double-blind, parallel dose control and multi-center phase II a dose exploration

Backgrounds: Yinlan Tiaozhi Capsule (YLTZ) is a prescription of traditional Chinese medicine (TCM) based on clinical experience. YLTZ have been used for the treatment of primary hyperlipidemia (HLP) in China, performing the disorder of blood lipids level, but few clinical studies have been conducted to assess its efficacy and safety in the treatment of primary HLP. Here, we designed a clinical trial combining Western Chinese medicine and TCM evaluation systems to evaluate the efficacy and safety of primary HLP.Methods: The study is designed as a randomized, double-blind, parallel dose control and multi-center clinical trial. Eligible subjects (n=120) will be allocated after satisfying the criteria (western medicine). Subjects will be randomized to receive YLTZ, or a placebo for 12-week treatment and with follow-up after treatment to record symptoms and signs and to collect serum samples for detecting the lipids level. At the same time, the syndrome differentiation criteria of TCM, such as body mass index, furred tongue and palpitation, will be recorded as determined by doctors of both Western and Chinese medicine. Participants will be instructed to comply with the protocol and to keep a daily record of symptoms. The primary and secondary outcomes and safety indicators will be used to evaluate the efficacy and safety of YLTZ in the treatment of primary HLP based on both Western Chinese medicine and TCM evaluation systems.Discussion: Previous studies were expected to evaluate whether the addition of YLTZ to standard routine treatment would enhance the treatment effectiveness and improve the primary HLP. However, this trial is focused on the outcome of lipids level, and we chose a range of outcome measurements to assess the improvement of relevant symptoms and signs. This trial is the first study designed to define and optimize the outcome measurements of lipids level of YLTZ in the treatment of patients with primary HLP. Trial registration: The trial has also been registered with the Center for Drug Evaluation (CDE, CTR20190061) and the China Clinical Trials Registry (ChiCTR1900021326).

A Rare Case of Evolocumab Induced Atrial Fibrillation

Evolocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) is a novel low-density lipoprotein (LDL) lowering agent that has been recently approved by the FDA to reduce the risk of myocardial infarction, stroke, and coronary revascularization in individuals with established atherosclerotic cardiovascular disease, alone or in combination with other lipid-lowering agents, and for treatment of patients with primary hyperlipidemia including familial hypercholesterolemia

A REVIEW: AZADIRACHTA INDICA AS ANTIHYPERLIPIDEMIC ACTIVITY

Antihyperlipidemic agents having various pharmacological actions are being tested clinically3. Elevated lipid levels result from increased absorption through the gut or enhanced endogenous synthesis and therefore two ways are feasible to reduce hyperlipidemia; to block endogenous synthesis or to decrease absorption. Whole plant of Azadirachta indica gives the Antihyperlipidemic activity. Several genetic conditions are known to responsible for primary Hyperlipidemia, such as lipoprotein lipase deficiency, apolipoprotein C-II deficiency etc. In our study we choose cholesterol diet which contains the common ingredients in our daily food. Cholesterol feeding has been often used to elevate serum or tissue cholesterol levels to assess the hypercholesterolemia- related metabolic disturbances in animals. Cholesterol feeding alone however does not affect the serum TG level. Keywords: Azadirachta indica, antihyperlipidemic, antiatherosclerotic activities, Maceration.