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Vitamine B3 veel beter dan medicijn bij hoog cholesterol en tegen aderverkalking*
Uit twee studies, een Engelse en een Amerikaanse blijkt het belang van vitamine B3 in de vorm van niacine in de behandeling van hoog cholesterol. In beide studies kregen patiënten die statines gebruikten om het cholesterol te verlagen als aanvulling vitamine B3 (niacine). In de Engelse studie kregen de deelnemers een jaar lang 2 gram niacine per dag of een placebo. Na dat jaar bleek de aderverkalking in de slagaders duidelijk minder te zijn, was het goede cholesterol (HDL) met 23% gestegen te zijn en was het slechte cholesterol met 19% gedaald. In de Amerikaanse studie kregen de deelnemers 14 maanden niacine of het medicijn ezetimibe. Ook hier deed niacine de aderverkalking duidelijk afnemen en steeg het goede cholesterol met 19%. Het medicijn deed het slechte cholesterol verder verlagen, maar deed niets aan de aderverkalking. Met dit medicijn kregen de deelnemers wel vijf maal meer kans op een hartaanval dan de deelnemers met de niacine. (5% versus 1%)
Drug that increases good cholesterol reduces clogging of arteries
A drug that raises levels of ‘good’ cholesterol, when taken in addition to standard statin therapy to lower ‘bad’ cholesterol, can reduce the furring up of arteries in patients with established heart disease, an Oxford University study has shown. The findings are published in the Journal of the American College of Cardiology.
‘This is the first clear evidence that a therapy to raise levels of good cholesterol when taken alongside statins can have a beneficial effect,’ says Dr Robin Choudhury of the Department of Cardiovascular Medicine at the University of Oxford, who led the study. ‘Using MRI scans, we have shown a reduction in the size of artery walls in patients after a year of treatment with nicotinic acid.
‘Our imaging study has identifying this as a very promising new prospect for treatment, and if the findings are borne out in ongoing larger studies this could benefit large numbers of people worldwide.
’ Heart disease is still the biggest killer in the Western world, and atherosclerosis – the ‘furring up’ or hardening of arteries – is closely linked to later heart attacks and strokes. The standard treatment for patients with atherosclerosis is to be prescribed statins. These drugs are effective in reducing the risk of heart attacks and stroke and work by lowering levels of ‘bad’ cholesterol, or low-density lipoprotein (LDL) cholesterol, which might otherwise get deposited in the arteries.
‘Good’ cholesterol, or high-density lipoprotein (HDL) cholesterol, is thought to help remove bad cholesterol from the arteries, and high levels of good cholesterol are associated with lower risk of heart disease. It has been thought that patients with low levels of good cholesterol might additionally benefit from treatments to raise these levels, but until now there has been little evidence to back this up.
Nicotinic acid, sometimes known as niacin, is one of the oldest drugs used for atherosclerosis and only fell out of favour as statins came to prominence. It is known to raise levels of good cholesterol in the blood.
Researchers at the Oxford Centre for Clinical Magnetic Resonance Research (OCMR) have been one of the leading groups to develop MRI methods for investigating vascular disease. So the Oxford team, along with colleagues from the University of Manchester, set out to see whether a high dose of nicotinic acid in addition to statins would affect the progression of atherosclerosis, using MRI to measure any changes in the thickness of the walls of the carotid artery (which takes blood to the head and neck) in particular, as well as other arteries and measures of major blood vessel function. 
71 patients, all with existing vascular disease, low levels of good cholesterol, and taking statins as prescribed by their GPs, were randomised to receive either 2 g of nicotinic acid or placebo for 1 year. MRI scans were performed before, after 6 months and after 12 months of the study.
After a year, the size of the carotid artery walls in patients who had received nicotinic acid was reduced compared with placebo. The area of the artery wall had got smaller by an average of 1.1 sq mm, while those receiving a placebo saw an average increase in the carotid artery wall of 1.2 sq mm.
Patients receiving nicotinic acid for 12 months showed an average 23% increase in levels of good cholesterol in the blood and a reduction in bad cholesterol of 19%. 
‘For years we had always been taught that atherosclerosis was a relentless progressive disease,’ says Dr Choudhury. ‘It is exciting to see a regression in established atherosclerosis.
’While this is evidence of a change that could be beneficial to patients, it is not a large-scale study of clinical outcomes to show whether taking nicotinic acid in addition to statins actually leads to fewer heart attacks, strokes or reduced mortality. 
But two such studies involving thousands of patients will report their results in the next few years (including one led by a different group at Oxford), which will give a clearer picture on whether therapies to increase good cholesterol should be added to strategies to combat heart disease.
‘Our results are very encouraging in that they have shown a very definite potential benefit, and will certainly increase the great interest the large outcome studies that are due to report in the next couple of years,’ says Dr Choudhury.
For more information please contact Dr Robin Choudhury on 01865 234663, 07789 481776, or robin.choudhury@cardiov.ox.ac.uk
Or the Press Office, University of Oxford on +44 (0)1865 280530 or press.office@admin.ox.ac.uk. 

Effect of niacin or ezetimibe added to chronic statin therapy on carotid intima media thickness: Study
In patients with or at high-risk for coronary artery disease and LDL (bad cholesterol) treated with statins to < 100mg/dL but low HDL (good cholesterol), adding medication to raise HDL was compared with lowering LDL further.
Patients were randomized to the addition of niacin (primarily to raise HDL), or ezetimibe (to further lower LDL cholesterol). Plaque buildup in the lining of the neck arteries was significantly reduced only in the niacin group.
In combination with statins, adding a medication that raises high-density lipoprotein (HDL) cholesterol was more effective in reversing artery wall plaque buildup and in reducing heart disease risk than adding a drug that lowers low-density lipoprotein (LDL) cholesterol, researchers reported today at the American Heart Association Scientific Sessions 2009.
In the study titled The Effect of Extended-release Niacin or Ezetimibe Added to Chronic Statin Therapy On Carotid Intima Media Thickness (ARBITER 6-HALTS), researchers found:
· Adding the cholesterol drug niacin to a statin improved HDL ("good") cholesterol levels and significantly reduced arterial plaque buildup within 8 months, with further improvement seen at the end of the study (14 months). 
· A second approach, adding ezetimibe to a statin, lowered LDL ("bad") cholesterol to a greater extent, but did not raise HDL. With it, there was no overall effect on arterial build up in the neck arteries.
· With ezetimibe, greater reductions in LDL cholesterol paradoxically were associated with more arterial buildup, a result opposite to that expected.
· The incidence of major cardiovascular events such as fatal and non-fatal heart attack was higher in the ezetimibe group as compared to the niacin group (5 percent vs. 1 percent). 
HDL And LDL Treatment Strategies (HALTS) was a prospective, randomized, parallel group, open-label, blinded endpoint study conducted at Walter Reed Army Medical Center in Washington, D.C., and Washington Adventist Hospital in Tacoma Park, Md. It included 363 adults (80 percent male, average age 68 years) with or at high risk for atherosclerotic cardiovascular disease.
All participants were on cholesterol-lowering statin drugs, and their LDL cholesterol was at the treatment goal of under 100 milligrams per deciliter (mg/dL) of blood. Their HDL cholesterol was lower than 50 mg/dL for men and 55 mg/dL for women. 
The researchers randomly assigned the subjects to receive either niacin or ezetimibe in addition to their usual statin. The primary endpoint was the change in the wall thickness of the carotid artery in the neck between the two groups of patients. In June, researchers halted the trial early because the primary endpoint was met. Specifically, 14-month follow-up data on 208 patients showed that in the niacin group, average HDL cholesterol rose from 42 mg/dL to 50 mg/dL and there was a significant regression in artery wall thickness. In the ezetimibe group, average LDL cholesterol levels dropped from 83 mg/dL to 66 mg/dL; however no overall change was found in average artery wall thickness. 
LDL cholesterol is generally linked to the buildup of plaque in the arteries, which makes them more likely to become narrowed, and can lead to heart attack or stroke. HDL cholesterol helps clear LDL cholesterol from the blood in a process called reverse cholesterol transport.
"These findings for ezetimibe are counter to the prevailing understanding of LDL cholesterol -- that lowering LDL cholesterol results in slowing of the atherosclerotic process as has been convincingly shown for other classes of lipid modifying drugs, such as statins and bile acid resins," said Allen J. Taylor, M.D. FAHA, principal investigator of the study and director of Advanced Cardiovascular Imaging and the Lipid/Prevention Clinic in the Department of Medicine (Cardiology) at Washington Hospital Center in Washington, D.C. 
In earlier studies demonstrating the protective effects of statins, researchers found strong associations between LDL cholesterol reduction and the prevention of cardiovascular disease. Consequently, many people now view LDL cholesterol reduction as a way to measure whether a treatment will be useful.
But HALTS researchers' findings "challenge the use of LDL reduction as a guaranteed surrogate for clinical performance, particularly for new clinical compounds, and in this particular case, ezetimibe," Taylor said. Patients should know their HDL numbers and, if they are low, ask their doctors if adding a treatment such as niacin is right for them once their LDL is treated to goal with a statin drug, he said. 
SOURCE American Heart Association (Januari 2010)


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