Ezetimibe monotherapy for cholesterol lowering in 2,722 people: systematic review and meta‐analysis of randomized controlled trials

Pandor, Abdullah; Ara, Roberta; Tumur, Indra; Wilkinson, Anna; Paisley, Suzy; Duenas, Alejandra; Durrington, Paul N.; Chilcott, Jim

doi:10.1111/j.1365-2796.2008.02062.x

Cited by 198 publications

(105 citation statements)

References 43 publications

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“…Ezetimibe has slight positive effects in lowering plasma fasting TG (8%) [153]. In addition, ezetimibe reduces the cholesterol content of both fasting and postprandial TG -rich lipoproteins, thereby lowering the concentrations of atherogenic remnant particles [154].…”

Section: Management Of Hypertriglyceridemiamentioning

confidence: 99%

Hypertriglyceridemia: a too long unfairly neglected major cardiovascular risk factor

Tenenbaum

Klempfner

Fisman

2014

Cardiovasc Diabetol

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The existence of an independent association between elevated triglyceride (TG) levels, cardiovascular (CV) risk and mortality has been largely controversial. The main difficulty in isolating the effect of hypertriglyceridemia on CV risk is the fact that elevated triglyceride levels are commonly associated with concomitant changes in high density lipoprotein (HDL), low density lipoprotein (LDL) and other lipoproteins. As a result of this problem and in disregard of the real biological role of TG, its significance as a plausible therapeutic target was unfoundedly underestimated for many years. However, taking epidemiological data together, both moderate and severe hypertriglyceridaemia are associated with a substantially increased long term total mortality and CV risk. Plasma TG levels partially reflect the concentration of the triglyceride-carrying lipoproteins (TRL): very low density lipoprotein (VLDL), chylomicrons and their remnants. Furthermore, hypertriglyceridemia commonly leads to reduction in HDL and increase in atherogenic small dense LDL levels. TG may also stimulate atherogenesis by mechanisms, such excessive free fatty acids (FFA) release, production of proinflammatory cytokines, fibrinogen, coagulation factors and impairment of fibrinolysis. Genetic studies strongly support hypertriglyceridemia and high concentrations of TRL as causal risk factors for CV disease. The most common forms of hypertriglyceridemia are related to overweight and sedentary life style, which in turn lead to insulin resistance, metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM). Intensive lifestyle therapy is the main initial treatment of hypertriglyceridemia. Statins are a cornerstone of the modern lipids-modifying therapy. If the primary goal is to lower TG levels, fibrates (bezafibrate and fenofibrate for monotherapy, and in combination with statin; gemfibrozil only for monotherapy) could be the preferable drugs. Also ezetimibe has mild positive effects in lowering TG. Initial experience with en ezetimibe/fibrates combination seems promising. The recently released IMPROVE-IT Trial is the first to prove that adding a non-statin drug (ezetimibe) to a statin lowers the risk of future CV events. In conclusion, the classical clinical paradigm of lipids-modifying treatment should be changed and high TG should be recognized as an important target for therapy in their own right. Hypertriglyceridemia should be treated.

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Section: Management Of Hypertriglyceridemiamentioning

confidence: 99%

Hypertriglyceridemia: a too long unfairly neglected major cardiovascular risk factor

Tenenbaum

Klempfner

Fisman

2014

Cardiovasc Diabetol

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“…Metaanalysis of 8 randomized, double-blind, placebo-controlled trials revealed that ezetimibe monotherapy for 12 weeks for the treatment of primary hypercholesterolemia was associated with a statistically significant reduction of the mean plasma LDL cholesterol levels by 18.58% as compared with a placebo 42) . Altmann and coworkers revealed Niemann-Pick C1-like 1 (NPC1L1) as a strong candidate for the ezetimibesensitive cholesterol transporter 43,44) .…”

Section: Novel Strategy For the Treatment Of Sitosterolemia With Ezetmentioning

confidence: 99%

Current Therapy for Patients with Sitosterolemia –Effect of Ezetimibe on Plant Sterol Metabolism

Tsubakio-Yamamoto

Nishida

Nakagawa-Toyama

et al. 2010

JAT

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Sitosterolemia is a rare, autosomal recessive inherited sterol storage disease associated with high tissue and serum plant sterol concentrations, caused by mutations in the adenosine triphosphate-binding cassette (ABC) transporter ABCG5 or ABCG8 genes. Markedly increased serum concentration of plant sterols. such as sitosterol and campesterol, cause premature atherosclerosis and massive xanthomas. Hitherto known treatments for sitosterolemia, including a low-sterol diet, bile-salt binding resins, ileal bypass surgery and low density lipoprotein (LDL) apheresis have not yielded sufficient reduction of serum plant sterol levels and many patients show a sustained elevation of plant sterol levels, subsequently developing premature atherosclerotic cardiovascular diseases. Ezetimibe, an inhibitor of intestinal cholesterol absorption through its binding to Niemann-Pick C1-like 1 (NPC1L1), has been widely used for decreasing serum LDL-cholesterol levels in patients with hypercholesterolemia. Ezetimibe also reduces the gastrointestinal absorption of plant sterols, thereby also lowering the serum concentrations of plant sterols. This pharmacological property of ezetimibe shows its potential as a novel effective therapy for sitosterolemia. In the current review, we discuss the current therapy for patients with sitosterolemia and present two Japanese adolescent patients with this disease, one of whom underwent percutaneous coronary intervention for accelerated coronary atherosclerosis. Ezetimibe administration in addition to conventional drug therapy successfully reduced serum sitosterol levels by 51.3% and 48.9%, respectively, in the two patients, demonstrating ezetimibe as a novel and potent treatment agent for sitosterolemia that could work additively with conventional drug therapy. J Atheroscler Thromb, 2010; 17:891-900.

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“…Other systematic reviews conducted so far have typically been focused on surrogate parameters rather than patient-relevant endpoints. Furthermore, most studies included in these reviews were short, lasting only a few weeks (11)(12)(13)(14)(15)(16)(36)(37)(38). The authors of a comparable review (17), also focusing on patientrelevant endpoints, arrived at the conclusion that, based on the available evidence, no additional or fewer benefits and no greater or lesser harm can be attributed to ezetimibe-statin combination therapy.…”

Section: Discussionmentioning

confidence: 99%

Ezetimibe-Statin Combination Therapy: Efficacy and Safety as Compared With Statin Monotherapy

Nußbaumer¹,

Glechner²,

Kaminski‐Hartenthaler³

et al. 2016

Deutsches Ärzteblatt International

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SUMMARYIntroduction: To date, most clinical comparisons of ezetimibe-statin combination therapy versus statin monotherapy have relied entirely on surrogate variables. In this systematic review, we study the efficacy and safety of ezetimibe-statin combination therapy in comparison to statin monotherapy in terms of the prevention of cardiovascular events in hyperlipidemic patients with atherosclerosis and/or diabetes mellitus.

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Ezetimibe monotherapy for cholesterol lowering in 2,722 people: systematic review and meta‐analysis of randomized controlled trials

Cited by 198 publications

References 43 publications

Hypertriglyceridemia: a too long unfairly neglected major cardiovascular risk factor

Hypertriglyceridemia: a too long unfairly neglected major cardiovascular risk factor

Current Therapy for Patients with Sitosterolemia –Effect of Ezetimibe on Plant Sterol Metabolism

Ezetimibe-Statin Combination Therapy: Efficacy and Safety as Compared With Statin Monotherapy

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