Prevention - SHARP

The clinical question

People with chronic kidney disease have a high risk of developing heart and circulatory diseases, including heart attacks or strokes. We know that reducing cholesterol levels in people with normal kidney function helps to prevent cardiovascular events. But previous trials had not shown this benefit in people with chronic kidney disease. This could be because they didn’t include enough people with the condition.

Researchers at the Oxford Clinical Trial Service Unit (CTSU) designed the SHARP trial (‘The Study of Heart and Renal Protection’) to find out if cholesterol lowering therapy could help prevent heart attacks and strokes in people with chronic kidney disease. The study was funded by Merck/Schering-Plough Pharmaceuticals, with additional support from a group of funders. This included the BHF through its support of the CTSU as part of the BHF Oxford Centre of Research Excellence.

What did the study involve?

The SHARP trial ran from 2003 to 2010. To ensure that the study was large enough to give a conclusive answer, the trial team collaborated with investigators across 18 countries. The trial recruited people with chronic kidney disease from 380 hospitals, including in the UK, mainland Europe, the USA, Australia, Malaysia and Thailand. Participants in the trial had lost at least 50% of their kidney function, with a third of them requiring dialysis treatment. None had a previous heart attack or surgery to unblock arteries supplying blood to their heart. 

Around 9,500 participants were randomly assigned to either:

• Receive daily cholesterol lowering treatment for around 5 years. The treatment was a combination tablet, containing a low dose of a statin, simvastatin, and a second cholesterol lowering drug, ezetimibe.
• Receive a placebo tablet.

The team monitored the participants through follow-up clinic visits. They tracked whether participants had experienced a suspected heart attack, stroke, other hospital admissions, or any side effects. 

What did the study show?

• Cholesterol lowering treatment caused a large drop in the levels of ‘bad cholesterol’ (LDL) in the blood of people with chronic kidney disease. 
• This was accompanied by a significant reduction in the risk of heart attacks, strokes or operations to unblock arteries, compared with people taking a placebo. 
• The treatment did not cause excessive side effects. 

Why is the study important?

Before SHARP, there was little information available about how to prevent heart and circulatory complications in people with chronic kidney disease. The study showed that around a quarter of all heart attacks, strokes and operations to open blocked arteries could be avoided in people with this condition by using a combination of simvastatin and ezetimibe to lower blood cholesterol levels.

Professor Colin Baigent, lead investigator of SHARP, gave his outlook on the trial: “It had been widely believed that raised cholesterol was not an important cause of heart disease or stroke in people with chronic kidney disease, so that lowering cholesterol might not be beneficial for them."

The results of SHARP have fed directly into UK and international guidelines for preventing cardiovascular disease in people with chronic kidney disease. Guidelines currently recommend that statins are used in people with this condition in the same way as they are used for other conditions that increase the risk of heart and circulatory diseases.

Grant details

"BHF Centre of Research Excellence"
Award reference:  RE/08/004/23915 - BHF Centre funding helped support the clinical trials unit involved in the running of this trial
Principal Investigator: Professor Colin Baigent, University of Oxford
Trial registration number: NCT00125593

Publication details

Baigent C, Landray MJ, Reith C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. 2011;377(9784):2181-92.