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21-02-2010 | Cardiology | Article

Ezetimibe has multiple effects beyond lipid-lowering

Abstract

Free abstract

MedWire News: The lipid-lowering drug ezetimibe has a wide range of beneficial effects on metabolic, oxidative, inflammatory, and renal parameters, a Japanese study has demonstrated.

The researchers say that these additional effects of ezetimibe, an inhibitor of Niemann-Pick C1-like protein, suggest the drug may be particularly useful in the treatment of hypercholesterolemic patients with the metabolic syndrome and chronic kidney disease.

Shusuke Yagi (The University of Tokushima) and co-workers enrolled 76 patients with inadequately controlled hypercholesterolemia, half of whom received ezetimibe 5 mg daily, in addition to any pre-existing drug or treatment for hyperlipidemia. The other half acted as controls, continuing on treatment as usual.

The two groups did not differ at baseline in any measured characteristic. By the end of the 8-week treatment period, however, the groups differed significantly with regard to a variety of anthropometric, lipid, metabolic, and vascular parameters.

Ezetimibe treatment was associated with significant reductions in low-density lipoprotein (LDL) cholesterol (from 146 to 111 mg/dl), body weight (from 65.3 to 64.2 kg), waist circumference (from 87.6 to 85.7 cm), and blood pressure (from 139/76 to 132/71 mmHg).

Ezetimibe was also associated with significant reductions in insulin resistance (from 4.73 to 3.83 units), urinary albumin excretion (from 38.6 to 26.1 mg/g creatinine), C-reactive protein (from 165 to 106 µg/dl), tumor necrosis factor-α (from 23.6 to 16.1 pg/ml), and urinary excretion of 8-hydroxy-2’-deoxyguanosine, a marker of oxidative stress (from 6.2 to 5.3 µg/g).

Meanwhile, ezetimibe brought about significant increases in the urinary excretion of nitrate and nitrite (from 18.8 to 25.6 nmol/g creatinine), indicating enhanced bioavailability of vascular nitric oxide.

None of these parameters changed significantly in control patients over the study period.

The researchers say their study shows that ezetimibe is an effective and potent lipid-lowering agent, bringing about an average 24.0% reduction in serum LDL-cholesterol levels.

“These data suggest that ezetimibe monotherapy is comparable to statin therapy and that the addition of ezetimibe to ongoing statin therapy further reduces serum LDL cholesterol levels,” they write.

Moreover, ezetimibe improved metabolic disorders, including obesity, hypertension, insulin resistance, and microalbuminuria.

“These findings suggest that [ezetimibe] produces a decrease in cardiovascular events by ameliorating metabolic syndrome and chronic kidney disease, crucial risk factors for cardiovascular diseases,” Yagi et al conclude.

They add: “Clinical and basic studies are underway in our laboratory to clarify the detailed mechanisms underlying the beneficial effects of ezetimibe on cardiovascular-renal diseases.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Joanna Lyford

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