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1.
Treating Coronary Artery Disease: Beyond Statins, Ezetimibe, and PCSK9 Inhibition.
Musunuru, K
Annual review of medicine. 2021;:447-458
Abstract
Statins, ezetimibe, and PCSK9 inhibitors are currently the standard of care for the prevention and treatment of coronary artery disease. Despite their widespread use, coronary artery disease remains the leading cause of death worldwide, a fact that pleads for the development of new protective therapies. In no small part due to advances in the field of human genetics, many new therapies targeting various lipid traits or inflammation have recently received approval from regulatory agencies such as the US Food and Drug Administration or fared favorably in clinical trials. This wave of new therapies promises to transform the care of patients at risk for life-threatening coronary events.
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2.
Bempedoic Acid: A New Tool in the Battle Against Hyperlipidemia.
Powell, J, Piszczatoski, C
Clinical therapeutics. 2021;(2):410-420
Abstract
PURPOSE This article discusses the pharmacology of bempedoic acid, the trials that led to United States Food and Drug Administration (FDA) approval of its use, and the overall safety and efficacy of this therapy in heterozygous familial hypercholesterolemia, established atherosclerotic cardiovascular disease (ASCVD), and hyperlipidemia. METHODS A database search of PubMed and ClinicalTrials.gov was conducted for articles published between January 2012 to September 2020 and containing the key words bempedoic acid, ezetimibe, Nexletol and Nexlizet. Trials from the CLEAR series were selected, as they played a pivotal role in the establishment of FDA approval, along with additional trials published after FDA approval, which provided novel evidence on the use of bempedoic acid in the treatment of hypercholesterolemia. Publications that were not randomized, controlled trials were not included in this review. Only randomized controlled trials in which ezetimibe was used in conjunction with bempedoic acid were included in this review as they were relevant to the new FDA approval of bempedoic acid. FINDINGS The findings of the present review show that bempedoic acid is both an effective and well-tolerated option for the treatment of hypercholesterolemia when used without ezetimibe in addition to standard therapy. It also appears that the combination with ezetimibe increases the cholesterol-lowering effect more than either agent alone when added to standard therapy. IMPLICATIONS Hypercholesteremia continues to be a major contributing factor leading to ASCVD. Bempedoic acid is an additional treatment option, along with both statins and diet and exercise, for reducing cholesterol levels and ASCVD events. With the new FDA approval, bempedoic acid may offer an effective therapy for reducing low-density lipoprotein cholesterol in patients at high risk for cardiovascular events due to established ASCVD or heterozygous familial hypercholesterolemia.
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3.
Rosuvastatin/Ezetimibe: A Review in Hypercholesterolemia.
Lamb, YN
American journal of cardiovascular drugs : drugs, devices, and other interventions. 2020;(4):381-392
Abstract
Rosuvastatin/ezetimibe combines two lipid-lowering agents: rosuvastatin, an HMG-CoA reductase inhibitor (i.e. statin) with particularly strong inhibitory effects on hepatic cholesterol synthesis, and ezetimibe, which inhibits the intestinal absorption of cholesterol. A fixed-dose combination (FDC) of rosuvastatin/ezetimibe is indicated as an adjunctive therapy to diet for the management of primary hypercholesterolemia in adults in numerous countries worldwide. In well-designed clinical trials evaluating the therapeutic efficacy of rosuvastatin/ezetimibe administered as either separate agents or as an FDC, rosuvastatin/ezetimibe was significantly more effective than rosuvastatin monotherapy (including at double the dose of rosuvastatin) or simvastatin/ezetimibe in reducing low-density lipoprotein cholesterol (LDL-C) and total cholesterol in adults with hypercholesterolemia. Furthermore, rosuvastatin/ezetimibe enabled significantly higher proportions of patients to achieve recommended LDL-C levels than rosuvastatin monotherapy or simvastatin/ezetimibe. Rosuvastatin/ezetimibe did not significantly differ from rosuvastatin monotherapy with respect to incidences of treatment-related or serious adverse events in these short-term trials and displayed a similar safety profile to simvastatin/ezetimibe. While additional cardiovascular outcomes data and head-to-head comparisons with atorvastatin/ezetimibe would be of interest, rosuvastatin/ezetimibe is a potent and generally well-tolerated drug combination that extends the range of options available for the pharmacological management of primary hypercholesterolemia in adults.
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4.
Low-Density Lipoprotein Cholesterol After an Acute Coronary Syndrome: How Low to Go?
Qamar, A, Libby, P
Current cardiology reports. 2019;(8):77
Abstract
PURPOSE OF REVIEW Recent advances in low-density lipoprotein cholesterol (LDL-C) lowering therapy have now enabled reducing LDL-C safely to very low levels. This review summarizes evidence from recent randomized clinical trials of intensive LDL-C lowering in patients with acute coronary syndrome (ACS) and provides a practical approach for LDL-C lowering to reduce the risk of recurrent ischemic events in this population. RECENT FINDINGS The risk of atherothrombotic events falls linearly with LDL-C level extending to very low achieved LDL-C levels (< 10 mg/dL) without apparent safety concerns. The addition of ezetimibe or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (i.e., evolocumab or alirocumab) to statin therapy lowers LDL-C to very low levels (≤ 30-50 mg/dL) with safety under the conditions studied and reduces the risk of recurrent cardiovascular events in patients with atherosclerotic cardiovascular disease. Current data support LDL-C lowering to levels below 70 mg/dL in patients post-ACS. Combination of high-intensity statins, ezetimibe, and if needed PCSK9 inhibitors merits consideration in such patients with ACS to optimize outcomes.
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5.
Practical guide for the use of PCSK9 inhibitors in Portugal.
Fontes-Carvalho, R, Marques Silva, P, Rodrigues, E, Araújo, F, Gavina, C, Ferreira, J, Morais, J
Revista portuguesa de cardiologia. 2019;(6):391-405
Abstract
Reducing low-density lipoprotein cholesterol (LDL-C) levels is one of the most important strategies for reducing the risk of cardiovascular events. However, in clinical practice, a high proportion of patients do not achieve recommended LDL-C levels through lifestyle and lipid-lowering therapy with statins and ezetimibe. PCSK9 inhibitors (PCSK9i) are a new therapeutic option that significantly (50-60%) reduces LDL-C levels, which in clinical trials translates into an additional reduction in risk for cardiovascular events, and has a good safety profile. However, it is a high-cost therapy, and therefore its use in clinical practice should take its cost-effectiveness into account. Priority should be given to use in patients at higher cardiovascular risk and those in whom high LDL-C levels persist despite optimal lipid-lowering therapy. This consensus document aims to summarize the main data on the clinical use of PCSK9i and to make recommendations for Portugal on the profile of patients who may benefit most from this therapy.
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6.
Familial Hypercholesterolemia in Children and Adolescents: Diagnosis and Treatment.
Maliachova, O, Stabouli, S
Current pharmaceutical design. 2018;(31):3672-3677
Abstract
Familial hypercholesterolemia is a hereditary genetic disorder predisposing in premature atherosclerosis and cardiovascular complications. Early diagnosis as well as effective treatment strategies in affected children are challenges among experts. Universal screening and cascade screening among families with familial hypercholesterolemia are being controversially discussed. Diagnosis of familial hypercholesterolemia in children and adolescents is usually based on clinical phenotype upon LDL-C levels and family history of premature cardiovascular and/or elevated LDL-C. Treatment approaches for familial hypercholesterolemia in the pediatric population are multidisciplinary and aim to reduce total cardiovascular risk. The most widely recommended and effective pharmacotherapy in the pediatric age group is currently statins. Ezetimibe and bile acid sequestrants are usually used as second-line agents. New therapeutic approaches, such as mipomersen and PCSK9 inhibitors seem promising. The main gap of evidence remains the lack of longitudinal follow up studies investigating cardiovascular outcomes, side effects, and effectiveness of treatment starting from childhood. Evidence would be expected in the near future by cohort and registry studies.
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7.
Optimizing Statins and Ezetimibe in Guideline-Focused Management.
Bin Abdulhak, AA, Robinson, JG
Cardiology clinics. 2018;(2):221-223
Abstract
Statins are essential medications in the management of patients with clinical atherosclerotic cardiovascular disease, and have been supported by numerous clinical trials. Emerging evidence suggests that adding ezetimibe to statin therapy is associated with a net benefit and improved hard clinical outcomes, particularly in patients with significantly elevated atherosclerotic cardiovascular disease risk and elevated low-density lipoprotein cholesterol levels.
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8.
Current status of lipid management in acute coronary syndrome.
Fujisue, K, Tsujita, K
Journal of cardiology. 2017;(2):101-106
Abstract
The development of coronary revascularization has dramatically improved early cardiovascular outcomes in patients with acute coronary syndrome (ACS). However, patients who have experienced myocardial infarction (MI) are at high risk of recurrence of cardiovascular events compared with those who are healthy or have stable coronary artery disease. Acute coronary events induce further inflammatory responses and plaque vulnerability in either a coronary culprit or whole vessels. The majority of data have supported the importance of coronary risk management to prevent secondary events. Dyslipidemia is common and one of the therapeutic targets in patients with ACS. Statins can reduce coronary plaque burden and lower the risk of cardiovascular death, recurrent MI, stroke, and coronary revascularization in patients with ACS. Growing evidence from clinical trials and meta-analyses supports early, intensive, and continuous therapy with statins in patients with ACS. Statins are accepted worldwide as the first-line lipid-lowering therapy as guidelines recommend. However, some patients do not reach the target level of low-density lipoprotein cholesterol by statins alone or are contra-indicated for statins. Recently, several clinical trials showed the further benefit of ezetimibe combined with statins on cardiovascular outcomes and coronary plaque regression in patients with ACS. In addition, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, novel and powerful lipid-lowering agents, have been developed and used in clinical settings. In this review, we summarize the present statin therapy, and refer to ezetimibe and PCSK9 as novel or additional non-statin strategies in the management of ACS.
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9.
The Treatment of Disorders of Lipid Metabolism.
Parhofer, KG
Deutsches Arzteblatt international. 2016;(15):261-8
Abstract
BACKGROUND Disorders of lipid metabolism are very common. They play an important role in the pathogenesis of atherosclerosis and can be effectively treated by lifestyle changes and drugs. METHODS This review is based on pertinent literature retrieved by a selective search. RESULTS The main disorders of lipid metabolism are LDL-hypercholesterolemia, hypertriglyceridemia, mixed hyperlipoproteinemia, and low HDL cholesterol. The lipoprotein(a) level can also be elevated either in isolation or in combination with other disorders of lipid metabolism. According to the current European recommendations, an LDL-cholesterol target value should be defined on the basis of the overall cardiovascular risk. If this risk is very high, as in patients with documented atherosclerosis, the target value should be set at <70 mg/dL (<1.8 mmol/L). If the risk is lower, higher target values can be set: <100 mg/dL (<2.6 mmol/L) or <115 mg/dL (<3.0 mmol/L). Lifestyle changes are an effective treatment mainly for patients with hypertriglyceridemia and mixed disorders of lipid metabolism. Lowering the LDL-cholesterol concentration with statins is by far the most important type of pharmacotherapy. Patients who cannot tolerate statins or whose cholesterol level is not adequately lowered can be given ezetimibe instead. PCSK9 antibodies have been available since the autumn of 2015; they can apparently lower the LDL-cholesterol level by more than 50% , but no endpoint trials have yet been reported. At present, they should only be given to carefully selected patients. Fibrates and omega-3 fatty acids have been found to prevent cardiovascular events in monotherapy trials but yield no added benefit when given together with statins. The design of these trials was faulty, however, and the utility of such combinations in patients with mixed disorders of lipid metabolism or hypertriglyceridemia cannot yet be definitively assessed. CONCLUSION There is a causal relationship between hypercholesterolemia and the risk of vascular and cardiovascular events. A reduction of LDL cholesterol lessens the risk of cardiovascular events.
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10.
Nonstatins and Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors: Role in Non-Familial Hypercholesterolemia.
Robinson, JG
Progress in cardiovascular diseases. 2016;(2):165-171
Abstract
After maximizing statin and lifestyle adherence, some patients may benefit from additional low-density lipoprotein cholesterol (LDL-C) lowering. The potential for net benefit from added therapy can inform nonstatin decision-making. Considering patient risk and the LDL-C level on statin, the additional potential cardiovascular disease (CVD) risk reduction benefit from further lowering LDL-C depends on the magnitude of LDL-C lowering from the nonstatin. Ezetimibe is the only nonstatin shown to reduce atherosclerotic CVD events added to a statin, albeit modestly, since it modestly reduces LDL-C by about 20%. Proprotein Convertase Subtilisin-Like/Kexin Type 9 mononclonal antibodies lower LDL-Cby 45-65%, but definitive CVD outcomes and safety trials are pending. Niacin and fenofibrate do not clearly reduce CVD events in statin-treated patients, and may increase adverse events. Bile acid sequestrants have not been evaluated in CVD outcome trials in statin-treated patients, and have an excess of adverse effects. Cost also plays a role in access to nonstatin therapy. These considerations may inform shared decision-making.