Ezetimibe

BACKGROUND: A large proportion of patients with heterozygous familial hypercholesterolemia (heFH) do not reach low-density lipoprotein cholesterol (LDL-c) levels advocated by international guidelines (<70 mg/dL or <100 mg/dL). OBJECTIVE: We set out to model which proportion of patients reach targets using conventional and novel therapies. METHODS: We performed a cross-sectional analysis in a large cohort of genetically identified heFH patients and calculated the proportion reaching treatment targets in four scenarios: (1) after 50% LDL-c reduction (representing maximal dose statin); (2) after 70% LDL-c reduction (maximal dose statin + ezetimibe); (3) additional 40% LDL-c reduction representing cholesteryl ester transfer protein inhibitor (CETPi); and (4) 60% LDL-c reduction (proprotein convertase subtilisin/kexin type 9 inhibitors [PCSK9i]), on top of scenario 2...

Importance: Human genetic studies have indicated that plasma lipoprotein(a) (Lp[a]) is causally associated with the risk of coronary heart disease (CHD), but randomized trials of several therapies that reduce Lp(a) levels by 25% to 35% have not provided any evidence that lowering Lp(a) level reduces CHD risk. Objective: To estimate the magnitude of the change in plasma Lp(a) levels needed to have the same evidence of an association with CHD risk as a 38.67-mg/dL (ie, 1-mmol/L) change in low-density lipoprotein cholesterol (LDL-C) level, a change that has been shown to produce a clinically meaningful reduction in the risk of CHD...

BACKGROUND: Chronic kidney disease (CKD) deteriorates the prognosis of patients undergoing percutaneous coronary intervention (PCI). Because coronary artery disease (CAD) is the major cause of death in CKD patients, cardiovascular risk reduction has been clinically important in CKD. We hypothesized intensive lipid-lowering with statin/ezetimibe attenuated coronary atherosclerotic development even in patients with CKD. METHODS: In the prospective, randomized, controlled, multicenter PRECISE-IVUS trial, 246 patients undergoing intravascular ultrasound (IVUS)-guided PCI were randomly assigned to receive atorvastatin/ezetimibe combination or atorvastatin alone (the dosage of atorvastatin was up-titrated to achieve the level of low-density lipoprotein cholesterol < 70 mg/dL)...

AIMS: The analysis evaluated the contemporary percentage of patients with established coronary heart disease (CHD) reaching the European guidelines recommended LDL-cholesterol (LDL-C) levels of less than 70 mg/dl and the threshold required for proprotein convertase subtlisin/kexin type 9 reimbursement in Italy (100 mg/dl). It also assessed how these percentages would change in case of diffuse use of ezetimibe. METHODS: The Dyslipidemia International Study II enrolled CHD patients aged at least 18 either on lipid-lowering therapy (LLT) for at least 3 months or not on LLT at the time of the lipid profile...

Low-density lipoprotein cholesterol (LDL-C) has been identified as a causative factor for atherosclerosis and related coronary heart disease, and as the main target for cholesterol- and lipid-lowering therapy. Statin drugs inhibit cholesterol synthesis in the liver and are typically the first line of therapy to lower elevated levels of LDL-C. On the other hand, a different drug, Ezetimibe, inhibits the absorption of cholesterol by the small intestine and provides a different mechanism of action. Many clinical trials have been carried out on safety and efficacy evaluation of cholesterol lowering drugs...

BACKGROUND AND AIMS: Patients with hyperlipidemia who are unable to tolerate optimal statin therapy are at increased cardiovascular risk due to ongoing elevations in low-density lipoprotein cholesterol (LDL-C). The objective of CLEAR Tranquility (NCT03001076) was to evaluate the efficacy and safety of bempedoic acid when added to background lipid-modifying therapy in patients with a history of statin intolerance who require additional LDL-C lowering. METHODS: This phase 3, multicenter, randomized, double-blind, placebo-controlled study enrolled patients with a history of statin intolerance and an LDL-C ≥100 mg/dL while on stable lipid-modifying therapy...

DYSIS II CHD was a longitudinal, observational study in 6794 patients from 18 countries. They were attending an outpatient physician appointment for coronary heart disease (CHD). 6370 patients (93.8%) were on active lipid lowering therapy (LLT). The mean atorvastatin dose equivalent was 25 mg per day and 10.5% received ezetimibe in combination with a statin. The mean low-density lipoprotein cholesterol (LDL-C) level was 88 mg/dL, with 29.4% of patients displaying a level below the 70 mg/dL target for very high-risk subjects...

OBJECTIVE: The nonalcoholic fatty liver disease fibrosis score (NFS) is comprised of unique metabolic risk indicators that may accurately predict residual cardiovascular (CV) risk in patients with established coronary disease and metabolic dysfunction. METHODS: We applied the NFS prospectively to 14,819 post-ACS patients randomized to ezetimibe/simvastatin (E/S) or placebo/simvastatin (P/S), in the IMPROVE-IT trial, using validated NFS cutoffs. The primary endpoint included CV death, myocardial infarction, unstable angina, revascularization or stroke...

The sorting receptor Sortilin functions in the regulation of glucose and lipid metabolism. Dysfunctional lipid uptake, storage, and metabolism contribute to several major human diseases including atherosclerosis and obesity. Sortilin associates with cardiovascular disease; however, the role of Sortilin in adipose tissue and lipid metabolism remains unclear. Here we show that in the low-density lipoprotein receptor-deficient (Ldlr-/- ) atherosclerosis model, Sortilin deficiency (Sort1-/- ) in female mice suppresses Niemann-Pick type C1-Like 1 (Npc1l1) mRNA levels, reduces body and white adipose tissue weight, and improves brown adipose tissue function partially via transcriptional downregulation of Krüppel-like factor 4 and Liver X receptor...

BACKGROUND: Individuals are at increased risk for cardiovascular events following an acute coronary syndrome (ACS). Effective management of hyperlipidemia, an associated risk factor, is essential for improving outcomes. We aimed to quantify the extent of hyperlipidemia and its treatment in ACS survivors in Hong Kong and Taiwan. METHODS: The multinational, observational Dyslipidemia International Study (DYSIS) II included patients hospitalized for an ACS. Lipid levels and use of lipid-lowering therapy (LLT) were evaluated at baseline and 4 months post-discharge...

PURPOSE OF REVIEW: Treatment of diabetic dyslipidemia is necessary because of its impact on cardiovascular disease, which is the leading cause of death in patients with diabetes. In the past, standard treatment of diabetic dyslipidemia focused only on correcting lipids. Although this remains the mainstay of treatment, because new antihyperglycemic treatments reduce cardiovascular events with minimal effect on dyslipidemia, a new approach is both timely and relevant. RECENT FINDINGS: LDL-lowering remains the focus of treatment for diabetic dyslipidemia, especially in patients with both diabetes and cardiovascular disease (CVD)...

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The authors review the association between diabetes mellitus (DM) and aberrations of lipid metabolism related to DM, diabetic dyslipidemia (DD). DM is considered as a major health burden worldwide and one of the most important modifiable cardiovascular disease (CVD) risk factors. This applies to both the developed and the developing countries, especially the latter. While patients with type 1 DM, 10% of all DM cases, usually do not have dyslipidemia, DD is frequent among patients with type 2 DM (T2DM) (prevalence > 75%) and is mainly a mixed dyslipidemia [increase in triglycerides (TGs), low high-density lipoprotein cholesterol (HDL-C), and small-dense (atherogenic), low-density lipoprotein cholesterol (LDL-C) particles]...

PURPOSE: The aim of this study was to evaluate the safety and efficacy of combination treatment of rosuvastatin with ezetimibe in patients with primary hypercholesterolemia. METHODS: This multicenter, randomized, double-blind study comprised a main study and an extension study. In the main study, the efficacy and safety of a combination of rosuvastatin (5, 10, and 20 mg) with ezetimibe (10 mg) were compared with those of rosuvastatin (5, 10, and 20 mg) alone. The subjects who achieved the National Cholesterol Education Program Adult Treatment Panel III LDL-C goal in the main study and agreed to a further study were enrolled for the extension study...

Autophagy activation exerts neuroprotective effects in the ischemic stroke model. Ezetimibe (Eze), a Niemann-Pick disease type C1-Like 1 (NPC1L1) pharmacological inhibitor, has been reported to protect hepatocytes from apoptosis via autophagy activation. In this study, we explored whether Eze could attenuate neuronal apoptosis in the rat model of middle cerebral artery occlusion (MCAO), specifically via activation of the AMPK/ULK1/autophagy pathway. Two hundred and one male Sprague-Dawley rats were subjected to transient MCAO followed by reperfusion...

Reducing the plasma levels of low-density lipoprotein-cholesterol (LDL-C) is critical for patients with coronary heart disease (CHD). Conventional treatment with statins alone may not achieve the goal of lowering LDL-C due to drug intolerance or resistance. The present study evaluated the effectiveness and safety of combining statin with another lipid-lowering agent in the management of dyslipidemia in CHD patients. A total of 180 patients with CHD were divided into three therapeutic groups (n=60 in each): Statin/colesevelam group (20 mg atorvastatin and 10 mg colesevelam daily), statin/ezetimibe group (20 mg atorvastatin and 10 mg ezetimibe daily) and high-intensity statin monotherapy group (30 mg atorvastatin daily)...

Purpose: Many studies of persistence involving fixed dose combinations (FDCs) of cardiovascular medicines have not adequately accounted for a user's prior experience with similar medicines. The aim of this research was to assess the effect of prior medicine experience on persistence to combination therapy. Patients and methods: Two retrospective cohort studies were conducted in the complete Pharmaceutical Benefits Scheme prescription claims dataset. Initiation and cessation rates were determined for combinations of: ezetimibe/statin; and amlodipine/statin...

BACKGROUND: Although high-intensity statin therapy (HIST) is recommended for most patients between 21 and 75 years of age with atherosclerotic cardiovascular disease (ASCVD), several recent analyses examining contemporary statin use trends have identified a clinical care gap in the utilization of HIST. OBJECTIVE: The objective of this study was to assess secular trends in lipid management for patients with ASCVD enrolled in a clinical pharmacy program within an integrated health care delivery system...

AIMS: Individuals with both diabetes mellitus (DM) and atherosclerotic cardiovascular disease (ASCVD) are at very high risk of cardiovascular events. This post-hoc analysis evaluated efficacy and safety of the PCSK9 inhibitor alirocumab among 984 individuals with DM and ASCVD pooled from 9 ODYSSEY Phase 3 trials. MATERIALS AND METHODS: Changes in low-density lipoprotein cholesterol (LDL-C) and other lipids from baseline to Week 24 were analysed (intention-to-treat) in 4 pools by alirocumab dosage (150 mg every 2 weeks [150] or 75 mg with possible increase to 150 mg every 2 weeks [75/150]), control (placebo/ezetimibe) and background statin usage (yes/no)...

PURPOSE OF REVIEW: There has been confusion following the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Lipid guidelines on the role of non-statin medications for cardiovascular prevention. RECENT FINDINGS: Several recent large trials have also now shown that lowering LDL with non-statins reduces cardiovascular events. In ASCVD patients on statins, adding ezetimibe or a PCSK9 inhibitor led to reductions in CV events in the IMPROVE IT, FOURIER, and most recently the ODYSSEY-OUTCOMES trials...