Day: 11/18/2010

Experimental Drug Has ‘Robust Effects’ on LDL and HDL Cholesterol

Posted by

0


Anacetrapib, a cholesteryl ester transfer protein inhibitor, had “robust effects” on LDL and HDL cholesterol levels in an industry-funded, phase III study presented Wednesday at the American Heart Association meeting and published in the New England Journal of Medicine.

Some 1600 adults who were already taking statins were randomized to receive 100 mg of anacetrapib or placebo daily for 18 months. At 6 months, the mean LDL level had dropped from 81 to 45 mg/dL with anacetrapib, compared with a drop from 82 to 77 mg/dL with placebo. Similarly, mean HDL increased significantly more with the drug (from 41 to 101 mg/dL) than with placebo (40 to 46 mg/dL).

Throughout treatment, the groups did not differ in cardiovascular events or in blood pressure, electrolyte, or aldosterone levels (such side effects kept anacetrapib’s predecessor, torcetrapib, from reaching the market).

The authors call for a larger clinical trial, noting that this study “is too small to provide definitive results regarding the overall safety or efficacy of anacetrapib.”

 

what is this?

Posted by

0


An image of a tube formation assay taken with an epifluorescence microscope. The tube formation assay is a 3D in vitro assay that mimics the formation of vasculature in vivo. NCI’s Dr. Enrique Zudaire is using this assay to discover new drugs to block tumor angiogenesis and tumor growth. The nuclei of endothelial cells appear blue. In green are the endothelial cells, which have been genetically engineered to express a green fluorescent protein. The thinner areas are hollow tubes while the thicker areas are cell clusters.

With Vitamin E Supplements, Risk Is Lower for Ischemic Stroke but Higher for Hemorrhagic Stroke

Posted by

0


Widespread use of vitamin E supplements is not recommended.

A plausible theory exists that vitamin E, an antioxidant, would prevent cardiovascular disease. The results of prospective randomized trials, however, have been mostly negative, and some have suggested harm, including excess risk for hemorrhagic stroke (JW Gen Med Nov 13 2008, JW Gen Med Sep 27 2007, and JW Gen Med Aug 2 2005). In this meta-analysis of nine randomized placebo-controlled trials with nearly 119,000 participants, investigators evaluated the effect of vitamin E supplementation on risk for overall, ischemic, and hemorrhagic strokes.

Seven trials provided information on overall stroke, and five trials each provided information on ischemic stroke and hemorrhagic stroke. Vitamin E had no effect on risk for overall stroke. Risk for ischemic stroke was 10% lower and risk for hemorrhagic stroke was 22% higher in vitamin E recipients than in placebo recipients; these differences were significant. Absolute risk differences, however, were small; 476 people would need to take vitamin E for at least 1 year to prevent one ischemic stroke, and 1250 people would need to take vitamin E to cause one hemorrhagic stroke.

Comment: Vitamin E supplementation has no effect on overall stroke, has minimal beneficial effect on ischemic stroke, and raises risk for hemorrhagic stroke. The authors advise against “indiscriminate widespread use of vitamin E” supplementation.

— Paul S. Mueller, MD, MPH, FACP

Published in Journal Watch General Medicine November 16, 2010

Nitrates and Nitrites in the Treatment of Ischemic Cardiac Disease

Posted by

0


Nossaman VE et al. – The organic nitrite, amyl of nitrite, was initially used as a therapeutic agent in the treatment of angina pectoris, but was replaced over a decade later by the organic nitrate, nitroglycerin (NTG), due to the ease of administration and longer duration of action. The administration of organic nitrate esters, such as NTG, continues to be used in the treatment of angina pectoris and heart failure since the birth of modern pharmacology. The nitrite anion, either from sodium nitrite or an intermediate nitroglycerin (NTG) form, may act as a storage form for nitric oxide (NO) and provide support for investigating the use of these agents in the treatment of ischemic cardiovascular states.

A Promising First Step for Combination Oral Therapy Against HCV

Posted by

0


In a short-term study, use of a protease inhibitor and a polymerase inhibitor together rapidly lowered HCV RNA levels.

Oral hepatitis C virus (HCV) protease inhibitors are expected to be approved in 2011. Adding these agents to standard HCV treatment (peginterferon plus ribavirin) improves the likelihood of sustained virologic response, but the interferon component must be given subcutaneously and has substantial side effects. In the industry-funded INFORM-1 study, researchers explored whether an interferon-free regimen containing two new oral anti-HCV agents — the protease inhibitor danoprevir, plus the nucleoside polymerase inhibitor RG7128 — could successfully suppress HCV replication.

Patients with chronic HCV genotype 1 infection but not cirrhosis or HIV infection were randomly assigned to receive placebo (n=14) or one of six different doses of danoprevir plus RG7128 (n=74) for 13 days. Treatment was directly observed in a clinical research unit.

At day 14, patients who received danoprevir plus RG7128 had marked declines in HCV RNA, with the median reduction ranging from 3.7 to 5.2 log10 IU/mL in the different dose groups; some patients achieved undetectable HCV RNA levels. At the highest doses tested, reductions in viral load were similar between patients who were treatment naive and those who had not responded to previous standard-of-care treatment. No phenotypic drug resistance was detected, although one patient with viral rebound did have a clone containing a danoprevir-resistance mutation.

Comment: This study shows that a combination of two oral investigational agents effectively suppresses HCV replication, at least in the short term. There has been an explosion of new direct-acting anti-HCV agents, and promising trial results were reported for many of them at the Liver Meeting this month in Boston. If longer-term studies show that combination therapy with new oral agents can eliminate viral replication, we may be able to cure HCV with pills alone. As an editorialist notes, we are “on the eve of a new era in HCV treatment.”


Published in Journal Watch Infectious Diseases November 17, 2010