Efficacy and safety of ezetimibe coadministered with statins: randomised, placebo-controlled, blinded experience in 2382 patients with primary hypercholesterolemia

Davidson, Michael; Ballantyne, Christie M.; Kerzner, Boris; Melani, Lorenzo; Sager, Philip T.; Lipka, Leslie J.; Strony, John; Suresh, Ramachandran; Veltri, Enrico P.

doi:10.1111/j.1368-5031.2004.00289.x

Cited by 123 publications

(80 citation statements)

References 22 publications

(42 reference statements)

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“…None of the patients treated with ezetimibe, including those who had previously suffered from statin-related myopathy, developed any treatment-related clinical adverse events or significant changes in hepatic enzymes (e.g., ALT and AST). A US placebo-controlled study of ezetimibe administered alone or in co-administration with statins showed statistically similar rates of adverse events between patients receiving ezetimibe monotherapy and those receiving a placebo and between those receiving statin monotherapy and those receiving co-administration with ezetimibe and any statin therapy 26) . Our findings confirm that ezetimibe has an excellent safety profile when administered alone or in co-administration with any statin.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Ezetimibe on Surrogate Markers of Cholesterol Absorption and Synthesis in Japanese Patients with Dyslipidemia

Hiramitsu¹,

Ishiguro²,

Matsuyama³

et al. 2010

JAT

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Aim:To demonstrate the clinical benefit of inhibiting intestinal cholesterol absorption, we evaluated the effects of ezetimibe on surrogate markers of cholesterol absorption and synthesis, lipid and glucose metabolism, and markers of obesity and inflammation. Methods: A total of 120 patients with dyslipidemia (46 men; mean age 66.5 years), who had not achieved the low density lipoprotein cholesterol (LDL-C) goal recommended by the Japan Atherosclerosis Society Guideline despite diet and exercise or any statin therapy, were enrolled and additionally treated with ezetimibe (10 mg/day) for 12 weeks. . Recent studies have elucidated the molecular mechanisms underlying intestinal cholesterol absorption, another potential therapeutic target for hypercholesterolemia. In 2000, Niemann-Pick C1 like 1 (NPC1L1), a transporter protein important for intestinal cholesterol absorption, was cloned. NPC1L1 is composed of 1,359 amino acids, possesses 13 transmembrane spanning IntroductionElevated low density lipoprotein cholesterol (LDL-C) is a major risk factor for cardiovascular diseases and its two sources, i.e., de novo synthesis in the liver and the absorption of dietary and bilialy cholesterol in the intestine, have offered important targets for the treatment of hypercholesterolemia. HMGCoA reductase inhibitors (statins), which target choAddress for correspondence: Shinya Hiramitsu, Fujita Ezetimibe STudy Assembly (FESTA) investigators group, Shiroshita-cho 2-35, Minami-ku, Nagoya 457-0047, Japan E-mail: hirazy@fujita-hu.ac. , together with a growing body of evidence that relates cholesterol absorption to the risk of cardiovascular events 4,5) , has made investigators more aware of the importance of controlling cholesterol absorption for the prevention of these cardiovascular events. Some investigators have reported increased intestinal cholesterol absorption in US and/or European individuals with a history of coronary artery disease 6) , obesity 7) , or type 2 diabetes mellitus 8) , although the relevance of this alteration to these and other pathologies remains to be determined.Based on these considerations, we evaluated the clinical benefit of ezetimibe and its effect on surrogate markers of cholesterol absorption and synthesis in Japanese patients with hypercholesterolemia in order to establish more efficient lipid-lowering therapy. MaterialsBetween June and December 2007, patients who presented to the outpatient clinic of Fujita Ezetimibe Study Assembly were enrolled if they had not achieved the LDL-C goal levels recommended in the 2007 Guideline of the Japan Atherosclerosis Society (JAS) 9) despite diet and exercise without anti-dyslipidemic agents for at least 4 weeks (ezetimibe monotherapy group) or had not achieved the LDL-C management goal levels despite at least 4 weeks of statin therapy (co-administration with ezetimibe and any statin). The study protocol was approved by the Fujita Health University Ethics Committee and all patients gave written informed consent. MethodsAt enrollment, all patients were examined ...

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Section: Discussionmentioning

confidence: 99%

The Effects of Ezetimibe on Surrogate Markers of Cholesterol Absorption and Synthesis in Japanese Patients with Dyslipidemia

Hiramitsu¹,

Ishiguro²,

Matsuyama³

et al. 2010

JAT

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“…Injury-induced neuroplasticity is also triggered at the onset of brain trauma, including neurogenesis, synaptogenesis, and angiogenesis (Davidson et al, 2004). Whether statins enhance these aspects of neuroplasticity after TBI remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Statins Increase Neurogenesis in the Dentate Gyrus, Reduce Delayed Neuronal Death in the Hippocampal CA3 Region, and Improve Spatial Learning in Rat after Traumatic Brain Injury

Goussev

et al. 2007

Journal of Neurotrauma

244

185

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Traumatic brain injury (TBI) remains a major public health problem globally. Presently, there is no way to restore cognitive deficits caused by TBI. In this study, we seek to evaluate the effect of statins (simvastatin and atorvastatin) on the spatial learning and neurogenesis in rats subjected to controlled cortical impact. Rats were treated with atorvastatin and simvastatin 1 day after TBI and daily for 14 days. Morris water maze tests were performed during weeks 2 and 5 after TBI. Bromodeoxyuridine (BrdU; 50 mg/kg) was intraperitoneally injected 1 day after TBI and daily for 14 days. Brain tissue was processed for immunohistochemical staining to identify newly generated cells and vessels. Our data show that (1) treatment of TBI with statins improves spatial learning on days 31-35 after onset of TBI; (2) in the non-neurogenic region of the hippocampal CA3 region, statin treatment reduces the neuronal loss after TBI, demonstrating the neuroprotective effect of statins; (3) in the neurogenic region of the dentate gyrus, treatment of TBI with statins enhances neurogenesis; (4) statin treatment augments TBI-induced angiogenesis; and (5) treatment with simvastatin at the same dose provides a therapeutic effect superior to treatment with atorvastatin. These results suggest that statins may be candidates for treatment of TBI.

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“…Ezetimibe/statin combination therapy was well-tolerated in 2,382 patients with primary hypercholesterolemia (37). Moreover, the safety and tolerability profiles for the ezetimibe/simvastatin and ezetimibe monotherapy groups were similar in a randomized, double-blind, placebocontrolled trial (38).…”

Section: Safety Of Ezetimibe In Humansmentioning

confidence: 97%

Ezetimibe, a Selective Inhibitor of the Transport of Cholesterol

Miura

Saku

2008

Intern. Med.

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Efficacy and safety of ezetimibe coadministered with statins: randomised, placebo-controlled, blinded experience in 2382 patients with primary hypercholesterolemia

Cited by 123 publications

References 22 publications

The Effects of Ezetimibe on Surrogate Markers of Cholesterol Absorption and Synthesis in Japanese Patients with Dyslipidemia

The Effects of Ezetimibe on Surrogate Markers of Cholesterol Absorption and Synthesis in Japanese Patients with Dyslipidemia

Statins Increase Neurogenesis in the Dentate Gyrus, Reduce Delayed Neuronal Death in the Hippocampal CA3 Region, and Improve Spatial Learning in Rat after Traumatic Brain Injury

Ezetimibe, a Selective Inhibitor of the Transport of Cholesterol

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