New drug combo to cut cardiovascular disease

A major international study to test whether a new combination treatment that increases good "HDL" cholesterol prevents heart attacks and strokes will start to recruit patients later this year.

It will recruit 20,000 patients with vascular disease from the UK, China and Scandinavia to investigate whether combining niacin with a new drug (MK-0524A) that minimises niacin's side-effects (chiefly facial flushing) can drive down still further the risk of serious heart attacks and strokes among people already taking treatment to lower their bad "LDL" cholesterol levels effectively.

It is being co-ordinated at Oxford University by the Clinical Trial Service Unit (CTSU), the research unit famous for running huge international studies, including the ground-breaking Heart Protection Study (HPS) which showed that a third of all heart attacks and strokes can be safely avoided in people at risk of vascular disease by using statins to lower LDL cholesterol.

The new study - called HPS2-THRIVE (Treatment of HDL to Reduce the Incidence of Vascular Events) - will be funded through a #42million grant to Oxford University by the pharmaceutical company Merck & Co., Inc. (Whitehouse Station, NJ, USA), developers of the combined HDL raising tablet. However, the CTSU has designed the study and will be responsible for coordinating it and analysing its results, independently of the funders.

Large-scale randomised studies have shown that lowering LDL cholesterol by about 1mmol/l for four to five years cuts the risks of heart attacks and strokes by about a quarter, and recent studies suggest that more intensive LDL-lowering can produce extra benefits. Even so, the risk among patients who already have vascular disease remains high, but there is limited scope for lowering LDL cholesterol much more.

So, the Oxford research team are taking a different approach by testing a combination tablet that can enable people to tolerate long-term use of an effective HDL cholesterol-raising treatment.

Dr Jane Armitage of the CTSU, one of the principal investigators, explained: "It has long been known that higher levels of good HDL cholesterol are correlated with lower risks of heart disease. Unfortunately, there is little evidence to date that raising HDL cholesterol with drugs is beneficial. Most studies have used fibrates, which raise HDL only modestly and results have been mixed.

"We have known for a long time that niacin is a very effective HDL raising agent. It increases HDL cholesterol by between a fifth and a quarter, as well as decreasing dangerous fatty substances in the blood called triglycerides by between a fifth and a third. But, the only large randomised study of niacin was conducted long before the introduction of statins, and patients find it difficult to take niacin long-term because it produces an uncomfortable side-effect of flushing. This flushing is caused by niacin dilating blood vessels in the skin through stimulating the release of a substance called prostaglandin D2.