Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The recently published Effect of Combination Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone on the Atherosclerotic Process in Patients With Heterozygous Familial Hypercholesterolemia (ENHANCE) trial seems to raise questions regarding the notion that lipid lowering is of benefit in the prevention and treatment of vascular disease. Before one can make this conclusion, a careful analysis of the trial, including the subjects included and the surrogate end point studied, is required. The results of this study should be taken in context with those of many other studies showing that lipid lowering by many approaches is beneficial. In conclusion, the public fury over this study, with physicians making unsupported statements to the press and on the Web, is unfortunate and should be discouraged in the future.
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PMID:Enhanced hype. 1863 4

Few clinical studies have focused on the efficacy of lipid-lowering therapies in patients > or = 65 years of age. The percentage of change from baseline in low-density lipoprotein (LDL) cholesterol and the percentage of patients achieving prespecified LDL cholesterol levels after 12 weeks of ezetimibe 10 mg plus atorvastatin versus up titration of atorvastatin were assessed in subjects > or = 65 years old with hyperlipidemia and at high risk of coronary heart disease. After stabilization of atorvastatin 10-mg therapy, 1,053 patients, > or = 65 years old, at high risk of coronary heart disease, with and without atherosclerotic vascular disease and a LDL cholesterol level that was not <70 or <100 mg/dl, respectively, were randomized to receive ezetimibe added to atorvastatin 10 mg for 12 weeks versus up titration to atorvastatin 20 mg for 6 weeks followed by up titration to atorvastatin 40 mg for an additional 6 weeks. Ezetimibe added to atorvastatin 10 mg resulted in significantly greater changes at week 6 in LDL cholesterol (p <0.001), significantly more patients with atherosclerotic vascular disease achieving a LDL cholesterol level of <70 mg/dl (p <0.001), and significantly more patients without atherosclerotic vascular disease achieving a LDL cholesterol level of <100 mg/dl (p <0.001) at weeks 6 and 12 compared to atorvastatin 20 mg or atorvastatin 40 mg. In addition, ezetimibe plus atorvastatin 10 mg resulted in significantly greater changes at week 6 in total cholesterol, triglycerides, non-high-density lipoprotein (HDL) cholesterol, apolipoprotein B (all p <0.001), and HDL cholesterol (p = 0.021) compared with atorvastatin 20 mg and significantly greater changes at week 12 in LDL cholesterol, non-HDL cholesterol, apolipoprotein A-I (p = 0.001), total cholesterol, apolipoprotein B (p <0.030), and HDL cholesterol (p <0.001) compared with atorvastatin 40 mg. Both treatments were generally well tolerated, with comparable safety profiles. In conclusion, adding ezetimibe to atorvastatin 10 mg produced significantly greater favorable changes in most lipids at 6 and 12 weeks and significantly greater attainment of prespecified LDL cholesterol levels than doubling or quadrupling the atorvastatin dose in patients > or =65 years old at high risk for coronary heart disease.
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PMID:Safety and efficacy of ezetimibe added to atorvastatin versus up titration of atorvastatin to 40 mg in Patients > or = 65 years of age (from the ZETia in the ELDerly [ZETELD] study). 2018 12

Ezetimibe is a lipid lowering medication that is able to inhibit dietary cholesterol. It can be used alone or in combination with statin therapy. The definitive IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) study will reveal the impact of ezetimibe in decreasing coronary vascular disease. The SHARP trial (Study of Heart And Renal Protection) will evaluate the effects of lowering low-density lipoprotein cholesterol with ezetimibe 10 mg and simvastatin 20 mg/day versus placebo in patients with chronic kidney disease. Recently, in a post-marketing analysis of reported adverse events, it was clearly demonstrated that ezetimibe or the combination of ezetimibe and simvastatin does not increase risk of cancer. The current evidence suggests that ezetimibe should be considered as a safe and effective lipid-lowering agent. This article projects the potential benefits of current and possible future ezetimibe clinical trials.
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PMID:Ezetimibe and recent clinical trials: a look on the bright side. 2037 76

The widespread clinical use of statins has contributed to significant reductions in the rate of cardiovascular morbidity and mortality over the past 3 decades, and statins are considered first-line therapy for the prevention and treatment of atherosclerotic vascular disease. Nevertheless, various other lipid-lowering agents can provide clinical benefit by supplementing or augmenting statin therapy in patients with severe hypercholesterolaemia or mixed dyslipidaemia, or by providing an alternative for patients who are intolerant to statins. Bile acid resins and niacin were prescribed for lipid modification for years before the introduction of the statins, and new data continue to emerge regarding their use in different patient groups and for specific conditions. Ezetimibe can be appropriate for patients whose primary lipid abnormality is an elevated LDL-cholesterol level, whereas the fibrates seem to be most beneficial in patients with low levels of HDL cholesterol and elevated triglycerides. At the end of 2012 and the beginning of 2013, the first microsomal triglyceride transfer protein inhibitor, lomitapide, and the first antisense therapy to target apolipoprotein B, mipomersen, were approved for the treatment of individuals with extremely elevated LDL-cholesterol levels caused by homozygous familial hypercholesterolaemia. Although two agents in the experimental class of cholesteryl ester transfer protein inhibitors have failed to show a benefit in clinical trials, newer drugs in this class could provide an additional strategy to address residual cardiovascular risk in patients treated with statins.
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PMID:Pharmacotherapies for lipid modification: beyond the statins. 2395 29

With the goal of decreasing low-density cholesterol (LDL-C) to mitigate risk of both primary and secondary cardiovascular outcomes, statins have been the cornerstone of therapy, significantly reducing the incidence of coronary atherosclerotic vascular disease. Previous studies suggest that adding other non-statin LDL-lowering agents may further lower LDL-C without negative side effects. Recent guidelines support the hypothesis that driving the LDL-C level below previously recommended targets may have a beneficial effect. Ezetimibe, a cholesterol absorption blocker that inhibits the Niemann-Pick C1-Like 1 (NPC1L1) receptor, has been the focus of recent trials that support its use in cardiovascular risk reduction. For patients not at goal on statin therapy alone, ezetimibe has proven to be a safe, well-tolerated medication that may be used as an adjunct to statin therapy to further reduce LDL-C, resulting in a significant mortality benefit.
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PMID:Role of Ezetimibe in Lipid-Lowering and Cardiovascular Disease Prevention. 2649 81

Statins are important for preventing adverse cardiovascular events in patients with both high and low risk of vascular disease, by reducing the levels of low-density lipoprotein cholesterol (LDL-C). However, statins dose-dependently increase adverse effects and increase the risk of type 2 diabetes. Previously, it was hypothesized this was caused by to off-target effects, but recent studies demonstrate it is caused by on-target effects. Nonetheless, the American guidelines recommend the use of high-intensity statin therapy, and extend its use to most people at risk of vascular diseases, particularly older people. In contrast, European, Korean, and Japanese committees have expressed concerns about the potential adverse effects of using high-intensity statins for lifelong periods in a large fraction of the population. Patients who have achieved LDL-C levels below currently recommended targets may still experience cardiovascular events, resulting from residual risk. Ezetimibe, PCSK9 inhibitors, inclisiran, and ANGPTL3 antisense oligonucleotides are promising alternative non-statin drugs. Of interest, cross-talk between hypercholesterolemia and the renin-angiotensin-system exists at multiple levels of insulin resistance and endothelial dysfunction. There are still unanswered questions on how to maximize the cardiometabolic benefits of statins in patients. We will discuss the results of randomized clinical trials, meta-analysis, and recent clinicopharmacogenetic studies, and propose practical guidelines to maximize the cardiometabolic benefits while reducing adverse effects and overcoming residual risk.
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PMID:Best Treatment Strategies With Statins to Maximize the Cardiometabolic Benefits. 2950 9