0
selected
-
1.
Current Drugs and Nutraceuticals for the Treatment of Patients with Dyslipidemias.
Scognamiglio, M, Costa, D, Sorriento, A, Napoli, C
Current pharmaceutical design. 2019;(1):85-95
Abstract
Coronary heart disease (CHD) remains the leading cause of disability and death in industrialized Countries. Among many conditions, which contribute to the etiology and progression of CHD, the presence of high low density lipoprotein-cholesterol (LDL-C) levels represents the major risk factor. Therefore, the reduction of LDL-C levels plays a key role in the management of patients with high or very high cardiovascular risk. Although statins represent the gold standard therapy for the reduction of cholesterol levels, these drugs do not allow to achieve target levels of LDL-C in all patients. Indeed, a significant number of patients resulted intolerants, especially when the dosage increased. The availability of new lipid-lowering drugs, such as ezetimibe and PCSK9 inhibitors, may represent an important alternative or complement to the conventional lipid-lowering therapies. However, long-term studies are still needed to define both efficacy and safety of use of these latter new drugs. Some nutraceuticals may become an adequate and effective support in the management of some patients. To date, several nutraceuticals with different mechanism of actions that provide a good tolerability are available as lipidlowering agents. In particular, the most investigated are red yeast rice, phytosterols, berberine, beta-glucans and soy. The aim of this review was to report recent data on the efficacy and safety of principle hypocholesterolemic drugs available and to evaluate the possible role of some nutraceuticals as support therapy in the management of patients with dyslipidemias.
-
2.
Lipid Management for the Prevention of Atherosclerotic Cardiovascular Disease.
Michos, ED, McEvoy, JW, Blumenthal, RS
The New England journal of medicine. 2019;(16):1557-1567
-
3.
Current status of familial hypercholesterolemia in Chinese populations.
Tomlinson, B, Hu, M, Chow, E
Current opinion in lipidology. 2019;(2):94-100
Abstract
PURPOSE OF REVIEW Heterozygous familial hypercholesterolemia often went unrecognized in China when population cholesterol levels were low, but rapid economic development has changed the situation. This review will discuss the current position of awareness, diagnosis, and management of familial hypercholesterolemia in Chinese populations. RECENT FINDINGS The phenotype of familial hypercholesterolemia in China and other Chinese populations has become similar to that in Western countries, although it may still be somewhat less severe. The prevalence in Chinese populations is also similar to that in other countries and it has been found in up to 7% of Chinese patients with premature coronary heart disease. Most of the mutations are in the low-density lipoprotein receptor gene but the pattern of mutations differs from that in Whites. Chinese patients may be more responsive to statins than Whites but patients with familial hypercholesterolemia are often undertreated. SUMMARY Increasing population cholesterol levels have changed the phenotype of familial hypercholesterolemia in China and Chinese patients now resemble those in Western countries. International initiatives are facilitating increased awareness and identification of cases and more effective management of the condition.
-
4.
Potential Therapeutic Value of Interleukin 1b-targeted Strategies in Atherosclerotic Cardiovascular Disease.
Viana-Huete, V, Fuster, JJ
Revista espanola de cardiologia (English ed.). 2019;(9):760-766
Abstract
Clinical trials have unequivocally shown that cholesterol-lowering drugs decrease the risk of atherosclerotic cardiovascular disease in an exceptionally wide range of individuals. Yet, even when treated optimally according to current standards, many individuals still experience life-threatening ischemic events. Emerging experimental and clinical evidence strongly suggests that persistent inflammation is a major driver of this residual risk, which has opened the door to the application of anti-inflammatory drugs for cardiovascular disease prevention. Here, we review our current knowledge of the biology of interleukin-1β, a key regulator of inflammation in atherosclerotic plaque and the target of the first clinical trial to demonstrate that an anti-inflammatory drug can effectively reduce cardiovascular risk. We discuss the challenges faced by interleukin-1β inhibitors and other anti-inflammatory compounds in their translation to the clinical scenario, and identify other potential targets within this signaling pathway that hold promise in the cardiovascular setting.
-
5.
Combining cholesterol-lowering strategies with imaging data: a visible benefit?
Koenig, W, Giovas, P, Nicholls, SJ
European journal of preventive cardiology. 2019;(4):365-379
Abstract
Coronary artery disease is characterised by the development of atherosclerotic plaques and is associated with significant morbidity and mortality on a global level. However, many patients with atherosclerosis are asymptomatic and the prediction of acute coronary events is challenging. The role of imaging studies in characterising plaque morphology and stability is emerging as a valuable prognostic tool, while providing evidence for the beneficial effects of cholesterol-lowering therapy on plaque burden. This review provides an overview of contemporary studies describing the value of imaging strategies for atherosclerotic plaques. Coronary angiography is commonly used in the clinical setting, but requires a significant radiation dose (similar to computed tomography). Magnetic resonance imaging evaluation of coronary vessels would avoid exposure to ionising radiation, but is not yet feasible due to motion artefacts. The roles of alternative imaging techniques, including grey-scale intravascular ultrasound, optical coherence tomography and near-infrared spectroscopy have emerged in recent years. In particular, grey-scale intravascular ultrasound has been effectively applied to detect changes in plaque burden and features of plaques predictive of rupture, as well as plaque characteristics during cholesterol-lowering therapy, providing novel insights into factors that may contribute to treatment effectiveness. Challenges and limitations to the use of imaging techniques are considered in this context, along with future imaging strategies.
-
6.
Cholesterol Lowering and Prevention of Stroke.
Hackam, DG, Hegele, RA
Stroke. 2019;(2):537-541
-
7.
Future role of proprotein convertase subtilisin/kexin type 9 inhibitors in preventive cardiology.
Mahmood, T, Shapiro, MD
Current opinion in cardiology. 2019;(5):519-525
Abstract
PURPOSE OF REVIEW The use of therapeutic monoclonal antibodies to target proprotein convertase subtilisin/kexin type 9 (PCSK9) represents a novel approach to the management of hypercholesteremia and prevention of atherosclerotic cardiovascular disease. We review the most recent literature relevant to PCSK9 inhibition with emphasis on how recent results and ongoing trials have and will continue to shape the use of this new therapeutic class in preventive cardiology. RECENT FINDINGS PCSK9 inhibitors reduce plasma lipoprotein(a) concentrations but a mechanistic understanding remains elusive. Evaluation of evolocumab for use in patients without prior myocardial infarction or stroke is underway (NCT03872401). Concerns regarding the cost-effectiveness of PCSK9 inhibitors have continued to thwart access to these drugs, though innovative models of care delivery and price reductions have improved this situation. Inclisiran, a small interfering ribonucleic acid (siRNA), reduces translation of PCSK9 and demonstrates more durable reductions in low-density lipoprotein-cholesterol (LDL-C). It is currently evaluated in the context of a phase III cardiovascular outcome trial in patients with established vascular disease (NCT03705234). SUMMARY The current scope of PCSK9 inhibitor therapy in preventive cardiology is limited to patients with familial hypercholesterolemia and/or established atherosclerotic cardiovascular disease. Future cardiovascular outcome trial results with PCSK9 blocking antibodies in primary prevention and with siRNA to PCSK9 in secondary prevention, improved understanding of the drivers of lipoprotein(a) reduction with PCSK9 inhibition, and cost-effectiveness will determine the future role of this therapeutic class.
-
8.
Subclinical coronary atherosclerosis and cardiovascular risk stratification in heterozygous familial hypercholesterolemia patients undergoing statin treatment.
Miname, MH, Bittencourt, MS, Nasir, K, Santos, RD
Current opinion in lipidology. 2019;(2):82-87
Abstract
PURPOSE OF REVIEW To discuss the heterogeneity of atherosclerotic cardiovascular disease (ASCVD) risk in heterozygous familial hypercholesterolemia and evidence and limitations of clinical risk scores and subclinical coronary atherosclerosis (SCA) imaging to evaluate risk. RECENT FINDINGS Risk evaluation in contemporary familial hypercholesterolemia cohorts needs to consider the cause of the familial hypercholesterolemia phenotype, for example the presence of autosomal molecular defects that impart a greater ASCVD risk than in polygenic hypercholesterolemia, prospective follow-up and the impact of statin treatment. As atherosclerosis is multifactorial, clinical scores like the Montreal familial hypercholesterolemia score and SAFEHEART risk equation have been proposed to stratify ASCVD in statin-treated, molecularly defined familial hypercholesterolemia individuals. However, these scores need further validation. SCA distribution in familial hypercholesterolemia individuals undergoing conventional lipid-lowering treatment is heterogeneous, with 45-50% of individuals not presenting any coronary artery calcification (CAC). One study suggests that the absence of CAC associates with no ASCVD events in asymptomatic familial hypercholesterolemia individuals undergoing statin therapy despite elevated residual LDL-cholesterol levels. In contrast, the presence of CAC was independently associated with ASCVD events. SUMMARY ASCVD risk is heterogeneous in statin-treated familial hypercholesterolemia individuals. Further studies are necessary to determine how risk stratification, especially with SCA detection, impacts on prescription of proprotein convertase subtilisin kexin type 9 inhibitors within a cost-constrained environment.
-
9.
LDL-cholesterol: The lower the better.
Pedro-Botet, J, Pintó, X
Clinica e investigacion en arteriosclerosis : publicacion oficial de la Sociedad Espanola de Arteriosclerosis. 2019;:16-27
Abstract
The reduction of low density lipoprotein-cholesterol (LDL-chol) has been associated with a decrease in cardiovascular morbidity and mortality. It has been demonstrated that there is no value of LDL-chol below which there ceases to be a preventive benefit with its reduction, and neither has it been observed that there is a higher incidence of secondary effects associated with lower concentrations of LDL-chol. Although there is a wide range of lipid-lowering drugs available, a high percentage of patients do not achieve the desired LDL-chol levels. The high-potency statins reduce the LDL-chol by 15-30%, and can double the percentage of patients that reach their desired level. This combination has shown to be safe and effective in the primary and secondary prevention of cardiovascular disease. Another option is the combination of statins with exchange resins, although this requires a more complex management. The inhibition of PCSK9 protein with monoclonal antibodies reduces the LDL-chol by more than 60%, and is effective in the prevention of cardiovascular disease. However, due to its cost, its use is restricted to patients with ischaemia or familial hypercholesterolaemia that do not achieve the desired levels with conventional drugs. The evidence base as regards the benefit and safety of achieving the desired levels of LDL-chol is very wide and is still increasing. In the next few years, it may be necessary to adjust the intensity of the hypercholesterolaemia treatment to the level of vascular risk of the patients, and to the level of reduction necessary to achieve the therapeutic targets. This will result in a more effective cardiovascular prevention and in a better quality of life, particularly in the large group of patients at higher vascular risk.
-
10.
An updated review of lipid-modifying therapy.
Simons, LA
The Medical journal of Australia. 2019;(2):87-92
Abstract
Statin drugs reduce low-density lipoprotein (LDL)-cholesterol (LDL-C) and cardiovascular risk. Ezetimibe may be used to supplement statin therapy, or used alone in cases of statin intolerance. Statin-associated side effects do occur, especially muscle symptoms and new onset diabetes, but they do not detract from the benefits of statin therapy. Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce LDL-C and cardiovascular risk. Evolocumab is subsidised in Australia for patients with familial hypercholesterolaemia when LDL-C is not adequately controlled with maximum doses of statin or ezetimibe or when statin therapy is contraindicated. Fenofibrate reduces triglycerides and cardiovascular risk in patients with type 2 diabetes when triglycerides are elevated and high-density lipoprotein (HDL) is low. A role for dietary omega-3 fatty acids and esters in reducing cardiovascular risk remains controversial. All cases of secondary cardiovascular disease prevention merit intensive lipid therapy, unless a contraindication exists. Lipid therapy is justified in cases of primary prevention when absolute risk is high, especially when lipids are highly elevated or when multiple risk factors are present. Clinical management requires a focus on the predominant lipid disorder present, namely hypercholesterolaemia, hypertriglyceridaemia or combined hyperlipidaemia. There is an ongoing problem of poor long term persistence on lipid therapy, as well as reduced awareness by practitioners of poor risk factor control.