scholarly journals Ezetimibe and Improving Cardiovascular Outcomes: Current Evidence and Perspectives

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Akshyaya Pradhan ◽  
Monika Bhandari ◽  
Rishi Sethi
Keyword(s):  
Statin Therapy ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Absorption ◽  
Cardiovascular Outcomes ◽  
Current Evidence ◽  
High Dose ◽  
Residual Cardiovascular Risk ◽  
Intestinal Cholesterol Absorption ◽  
Cholesterol Absorption Inhibitor

Low-density lipoprotein lowering with statins has convincingly and consistently proven to reduce cardiovascular events in both primary and secondary prevention. However, despite high-dose statin therapy, residual cardiovascular risk remains and many patients also do not tolerate statins. Ezetimibe was initially projected as a frontline alternative to statin. It is an intestinal cholesterol absorption inhibitor with modest LDL lowering effects. But, major studies failed to demonstrate any beneficial effect of CV outcomes, and the drug was relegated to oblivion. IMPROVE-IT, a contemporary, large, and well-designed trial, unequivocally demonstrated reduction in CV outcomes with ezetimibe when added to statin therapy. The benefits are seen in both sexes, elderly, CKD, diabetes mellitus, and in patients with prior CABG. It also reduces biomarkers and induces plaque regression like statins. The drug has now established itself as an add-on therapy to statin when monotherapy fails to achieve LDL goals and when it is not tolerated. The combination therapy has excellent safety and efficacy record. It has now been endorsed by major guidelines too in management of dyslipidemia. Yes, ezetimibe can indeed improve cardiovascular outcomes!

scholarly journals Triglycerides and Cardiovascular Outcomes—Can We REDUCE-IT ?

2020 ◽  
Vol 29 (01) ◽  
pp. 002-011 ◽  
Author(s):  
Akshyaya Pradhan ◽  
Monika Bhandari ◽  
Pravesh Vishwakarma ◽  
Rishi Sethi
Keyword(s):  
Fatty Acids ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cardiovascular Outcomes ◽  
High Dose ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Residual Cardiovascular Risk ◽  
Beneficial Effects ◽  
Artery Disease

AbstractThe causal linkage between triglycerides and coronary artery disease has been controversial. Most of the trials hitherto have shown marginal or no beneficial effects of reduction of triglycerides (with fibrates) on top of low-density lipoprotein (LDL) reduction. But a significant residual cardiovascular risk remains even after use of high dose of statins. Omega-3 fatty acids have been shown to reduce triglyceride levels and some old trials have shown the benefits of fish oils in reducing cardiovascular events. However, barring a few trials most of the large trials of omega-3 fatty acids are negative. Recently, few large trials have been conducted to see the effects of high dose omega-3 fatty acids on cardiovascular outcomes and some of them have shown promising results on top of LDL reduction.

scholarly journals Cis- and Trans-Palmitoleic Acid Isomers Regulate Cholesterol Metabolism in Different Ways

2020 ◽  
Vol 11 ◽  
Author(s):  
Wen-wen Huang ◽  
Bi-hong Hong ◽  
Kai-kai Bai ◽  
Ran Tan ◽  
Ting Yang ◽  
...  
Keyword(s):  
Bile Acids ◽  
Palmitoleic Acid ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Absorption ◽  
Cholesterol Homeostasis ◽  
High Dose ◽  
Intestinal Cholesterol Absorption ◽  
Preventable Risk Factor

Hypercholesterolemia is a preventable risk factor for atherosclerosis and cardiovascular disease. However, the mechanisms whereby cis-palmitoleic acid (cPOA) and trans-palmitoleic acid (tPOA) promote cholesterol homeostasis and ameliorate hypercholesterolemia remain elusive. To investigate the effects of cPOA and tPOA on cholesterol metabolism and its mechanisms, we induced hypercholesterolemia in mice using a high-fat diet and then intragastrically administered cPOA or tPOA once daily for 4 weeks. tPOA administration reduced serum cholesterol, low-density lipoprotein, high-density lipoprotein, and hepatic free cholesterol and total bile acids (TBAs). Conversely, cPOA had no effect on these parameters except for TBAs. Histological examination of the liver, however, revealed that cPOA ameliorated hepatic steatosis more effectively than tPOA. tPOA significantly reduced the expression of 3-hydroxy-3-methyl glutaryl coenzyme reductase (HMGCR), LXRα, and intestinal Niemann-Pick C1-Like 1 (NPC1L1) and increased cholesterol 7-alpha hydroxylase (CYP7A1) in the liver, whereas cPOA reduced the expression of HMGCR and CYP7A1 in the liver and had no effect on intestinal NPC1L1. In summary, our results suggest that cPOA and tPOA reduce cholesterol synthesis by decreasing HMGCR levels. Furthermore, tPOA, but not cPOA, inhibited intestinal cholesterol absorption by downregulating NPC1L1. Both high-dose tPOA and cPOA may promote the conversion of cholesterol into bile acids by upregulating CYP7A1. tPOA and cPOA prevent hypercholesterolemia via distinct mechanisms.

scholarly journals Serum PCSK9 Levels Distinguish Individuals Who Do Not Respond to High-Dose Statin Therapy with the Expected Reduction in LDL-C

2014 ◽  
Vol 2014 ◽  
pp. 1-3 ◽  
Author(s):  
Beth A. Taylor ◽  
Gregory Panza ◽  
Linda S. Pescatello ◽  
Stuart Chipkin ◽  
Daniel Gipe ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Present Report ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Statin Treatment ◽  
High Dose ◽  
Drug Compliance ◽  
Atorvastatin Treatment ◽  
Pill Counts ◽  
And Gender

The purpose of the present report was to examine whether proprotein convertase subtilisin/kexin type 9 (PCSK9) levels differ in individuals who do not exhibit expected reductions in low density lipoprotein cholesterol (LDL-C) with statin therapy. Eighteen nonresponder subjects treated with 80 mg atorvastatin treatment for 6 months without substantial reductions in LDL-C (ΔLDL-C: 2.6 ± 11.4%) were compared to age- and gender-matched atorvastatin responders (ΔLDL-C: 50.7 ± 8.5%) and placebo-treated subjects (ΔLDL-C: 9.9 ± 21.5%). Free PCSK9 was marginally higher in nonresponders at baseline(P=0.07)and significantly higher in atorvastatin responders after 6 months of treatment(P=0.04). The change in free PCSK9 over 6 months with statin treatment was higher(P<0.01)in atorvastatin responders (134.2 ± 131.5 ng/mL post- versus prestudy) than in either the nonresponders (39.9 ± 87.8 ng/mL) or placebo subjects (27.8 ± 97.6 ng/mL). Drug compliance was not lower in the nonresponders as assessed by pill counts and poststudy plasma atorvastatin levels. Serum PCSK9 levels, both at baseline and in response to statin therapy, may differentiate individuals who do versus those who do not respond to statin treatment.

Molecular Insights into the Mechanisms Underlying the Cholesterol- Lowering Effects of Phytosterols

2019 ◽  
Vol 26 (37) ◽  
pp. 6704-6723 ◽  
Author(s):  
Lídia Cedó ◽  
Marta Farràs ◽  
Miriam Lee-Rueckert ◽  
Joan Carles Escolà-Gil
Keyword(s):  
Bile Acids ◽  
Molecular Mechanisms ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Absorption ◽  
Plant Sterols ◽  
Intestinal Lumen ◽  
Low Density ◽  
Intestinal Cholesterol Absorption ◽  
Cholesterol Lowering

Dietary phytosterols, which comprise plant sterols and stanols, reduce plasma Low-Density Lipoprotein-Cholesterol (LDL-C) levels when given 2 g/day. Since this dose has not been reported to cause health-related side effects in long-term human studies, food products containing these plant compounds are used as potential therapeutic dietary options to reduce LDL-C and cardiovascular disease risk. Several mechanisms have been proposed to explain the cholesterol-lowering action of phytosterols. They may compete with dietary and biliary cholesterol for micellar solubilization in the intestinal lumen, impairing intestinal cholesterol absorption. Recent evidence indicates that phytosterols may also regulate other pathways. Impaired intestinal cholesterol absorption is usually associated with reduced cholesterol transport to the liver, which may reduce the incorporation of cholesterol into Very-Low- Density Lipoprotein (VLDL) particles, thereby lowering the rate of VLDL assembly and secretion. Impaired liver VLDL production may reduce the rate of LDL production. On the other hand, significant evidence supports a role for plant sterols in the Transintestinal Cholesterol Excretion (TICE) pathway, although the exact mechanisms by which they promote the flow of cholesterol from the blood to enterocytes and the intestinal lumen remains unknown. Dietary phytosterols may also alter the conversion of bile acids into secondary bile acids, and may lower the bile acid hydrophobic/hydrophilic ratio, thereby reducing intestinal cholesterol absorption. This article reviews the progress to date in research on the molecular mechanisms underlying the cholesterol-lowering effects of phytosterols.

scholarly journals Recent Molecular Mechanisms and Beneficial Effects of Phytochemicals and Plant-Based Whole Foods in Reducing LDL-C and Preventing Cardiovascular Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 784
Author(s):  
Salman Ul Islam ◽  
Muhammad Bilal Ahmed ◽  
Haseeb Ahsan ◽  
Young-Sup Lee
Keyword(s):  
Cardiovascular Disease ◽  
Molecular Mechanisms ◽  
Cardiovascular Health ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Absorption ◽  
Intestinal Cholesterol Absorption ◽  
Beneficial Effects ◽  
Treatment And Prevention ◽  
Whole Foods

Abnormal lipid metabolism leads to the development of hyperlipidemia, a common cause of multiple chronic disorders, including cardiovascular disease (CVD), obesity, diabetes, and cerebrovascular disease. Low-density lipoprotein cholesterol (LDL-C) currently remains the primary target for treatment of hyperlipidemia. Despite the advancement of treatment and prevention of hyperlipidemia, medications used to manage hyperlipidemia are limited to allopathic drugs, which present certain limitations and adverse effects. Increasing evidence indicates that utilization of phytochemicals and plant-based whole foods is an alternative and promising strategy to prevent hyperlipidemia and CVD. The current review focuses on phytochemicals and their pharmacological mode of actions for the regulation of LDL-C and prevention of CVD. The important molecular mechanisms illustrated in detail in this review include elevation of reverse cholesterol transport, inhibition of intestinal cholesterol absorption, acceleration of cholesterol excretion in the liver, and reduction of cholesterol synthesis. Moreover, the beneficial effects of plant-based whole foods, such as fresh fruits, vegetables, dried nuts, flax seeds, whole grains, peas, beans, vegan diets, and dietary fibers in LDL-C reduction and cardiovascular health are summarized. This review concludes that phytochemicals and plant-based whole foods can reduce LDL-C levels and lower the risk for CVD.

Abstract 13849: Impact of Statin-Ezetimibe Combination on Coronary Atheroma Progression/Regression in Patients With and Without Prior Statin Therapy - Subanalysis of PRECISE-IVUS Trial

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Kenichi Tsujita ◽  
Kenshi Yamanaga ◽  
Seigo Sugiyama ◽  
Hideki Shimomura ◽  
Takuro Yamashita ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Coronary Intervention ◽  
Cholesterol Absorption ◽  
Coronary Plaque ◽  
Regression Effect ◽  
Atheroma Volume ◽  
Plaque Regression ◽  
Coronary Atheroma

Introduction: IMPROVE-IT trial showed the clinical benefit of statin-ezetimibe (EZE) combination appeared to be pronounced in patients with prior statin therapy. On the other hand, the PRECISE-IVUS ( P laque RE gression with C holesterol absorption I nhibitor or S ynthesis inhibitor E valuated by I ntra V ascular U ltra S ound) trial was a prospective, randomized, controlled, multicenter study evaluating the effects of EZE addition to atorvastatin (atorva), compared with atorva monotherapy, on coronary atherosclerosis evaluated by IVUS and lipid profile. Hypothesis: We hypothesized that the antiatherosclerotic effect of atorva-EZE combination was pronounced in patients with statin pretreatment. Methods: 246 patients undergoing IVUS-guided percutaneous coronary intervention were randomized to EZE/atorva combination or atorva alone. The dosage of atorva was uptitrated with a treatment goal of lowering low-density lipoprotein cholesterol (LDL-C) below 70mg/dL. Serial volumetric IVUS was performed at baseline and 9–12 months follow-up to quantify the coronary plaque response in 202 patients. We compared the IVUS endpoints in all subjects, stratified by the presence of statin pretreatment. Results: The baseline LDL-C level (100.7±23.1mg/dL vs. 116.4±25.9mg/dL, p<0.001) and lathosterol (55 [38 to 87])μg/100mg TC vs. 97 [57 to 149]μg/100mg TC, p<0.001) was significantly lower, and campesterol/lathosterol ratio (3.9 [2.4 to 7.4] vs. 2.6 [1.5 to 4.1], p<0.001) was significantly accelerated in patients with statin pretreatment. Contrary to the patients without statin pretreatment (-1.3 [-3.1 to -0.1]% vs. -0.9 [-2.3 to 0.9]%, p=0.12), the atorva-EZE combination showed the significantly stronger reduction in delta percent atheroma volume, compared with atorva alone, in patients with statin pretreatment (-1.8 [-3.6 to -0.3]% vs. -0.1 [-1.6 to 0.8]%, p=0.002). Conclusions: Compared to atorva alone, atorva-EZE combination demonstrated stronger regression effect in coronary atheroma volume especially in patients with statin pretreatment. Compensatory accelerated cholesterol absorption might be associated with reduced coronary plaque regression. Low-dose statin-EZE combination might be a promising option in statin-hyporesponder.

Ease: Ezetimibe Add-on to Statin for Effectiveness Trail

2006 ◽  
Vol 4 (1) ◽  
pp. 32-35
Author(s):  
Linda Brokes
Keyword(s):  
National Cholesterol Education Program ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Absorption ◽  
Adult Treatment ◽  
Adult Treatment Panel ◽  
Community Based ◽  
Cholesterol Absorption Inhibitor ◽  
Additional Reduction

Results from the largest community-based clinical trial to date, involving more than 3000 patients, has shown that adding the cholesterol absorption inhibitor ezetimibe to ongoing stable statin therapy in patients with hypercholesterolemia produces a significant additional reduction in low-density lipoprotein (LDL)- cholesterol compared with adding a placebo.[1] In addition, more patients who added ezetimibe achieved their National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) If LDL-cholesterol targets. The Ezetimibe Add-on to Statin for Effectiveness (EASE) trial included a total of 3030 patients on a stable dose of a statin but not yet at their NCEP ATP III LDLcholesterel goal,[2]

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