19 May 2003 19:00 GMT

by Larry Schuster

San Diego - A five-year study of a cholesterol-lowering drug in patients with diabetes has found that reducing cholesterol levels below currently approved US targets significantly reduces the risk of heart attack and related vascular events. The findings suggest that cholesterol target levels may be set too high for diabetes patients.

The current US target for acceptable levels of circulating cholesterol is set at 100 mg/dl, but even patients with levels below this were found to have their risk of heart attack and related disorders cut by up to a third following treatment with a statin, or cholesterol-reducing drug, called simvastatin.

A group of 4,000 subjects were enrolled on the five-year placebo-controlled trial led by Rory Collins, professor of medicine and epidemiology at the University of Oxford, UK. The results support continued and increasingly aggressive efforts to lower cholesterol in most diabetic patients, regardless of the national target points that have been set, the researchers conclude. They also point to a possible increased role for similar drugs, stronger drugs or combinations of another drug with a statin for diabetics who are resistant to cholesterol lowering.

The same study found no benefit from taking antioxidant vitamins E, C and beta-carotene, says Collins, who presented data here at the annual meeting of the American Association of Clinical Endocrinologists.

The diabetes trial is part of the Heart Protection Study of cholesterol-lowering therapy in diabetes and other high-risk conditions, which reported similar findings about a year ago in more than 20,000 patients. For that study, patients aged 40-80 with a history of occlusive vascular disease or diabetes were eligible provided their own doctors did not consider statin therapy clearly indicated.

These data reported at the meeting, however, represent the first findings from a large group composed exclusively of diabetic patients with no previous history of coronary heart disease.

Specifically, Collins and colleagues found that daily doses of 40mg of the statin reduced the risk of major vascular events by at least a quarter. But taking into account various artefacts, including people who stopped taking the drug or took the drug when they were not supposed to, Collins estimates that the actual risk reduction is closer to one third. Major vascular events included non-fatal myocardial infarction or coronary death, non-fatal or fatal stroke and coronary or non-coronary revascularization.

The reduction in such events occurred regardless of how well controlled the diabetes was, regardless of the level of cholesterol when the therapy was initiated, and regardless of whether patients had a previous record of symptoms.

"Their lipid levels are not that different from the general population, but their risk is higher," Collins told BioMedNet News.

Gene Barrett, president elect of the American Diabetes Association (ADA), says that the American Heart Association has recently recommended viewing the treatment of diabetes as equivalent to a coronary disease event. The ADA agrees with this, says Barrett, and supports the need for increasingly aggressive therapy.

Barrett, professor of medicine at the University of Virginia, Charlottesville, Virginia, says current AHA guidelines call for a target of below 100 mg/dl. Whether to recommend further reductions has remained unresolved because there were no conclusive data that it would help. This new study may provide those data.

Collins says the results "Reinforce the value of finding new drugs that can further reduce low density lipoproteins [LDLs] on top of statins, rather than just taking people down to a target level which seems not to be low enough."

Statins decrease the body's synthesis of cholesterol. Other drugs may be valuable add-ons in the therapy. For example, Ezetimibe, which was approved by the Food and Drug Administration in October 2002, decreases absorption of cholesterol in the intestine. When used with simvastatin, the drug can decrease cholesterol by another 15-20%, says Collins, who calls the drug "very promising."

The results appear to further confirm and extend the results of several previous studies: the Scandinavian Simvastatin Survival Study (4S), the West of Scotland Coronary Prevention Study (WOSCOPS), and the Cholesterol and Recurrent Events (CARE) study. Those studies showed the benefits of cholesterol lowering in patients with either high cholesterol and established cardiovascular heart disease, high cholesterol but no disease, or 'normal' cholesterol levels but myocardial ischemia.