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The SHARP study involved almost 9,500 volunteers aged 40 or over with chronic kidney disease recruited from 380 hospitals in 18 countries. Volunteers were randomly allocated to take either cholesterol-lowering therapy with a tablet containing ezetimibe 10mg daily and simvastatin 20mg daily, or matching dummy "placebo" tablets for an average of 5 years.

QS: What is SHARP?

Colin Baigent: SHARP is a randomised trial of cholesterol lowering treatment in 9000 patients with chronic kidney disease. At the beginning, over 9000 volunteers were asked either to take an active cholesterol lowering treatment or a matching Dummy placebo. They did that for over five years and at the end, we look to see what had happened to patients during that time. And in particular, we were interested in whether there was any reduction in the risk of a heart attack or stroke.

We wanted to do the SHARP study, because we were well aware that kidney patients have a very high risk of cardiovascular disease. We want to be able to do something about this. Very little is known about how to manage this disease and treatment may be somewhat haphazard by running a really large study looking at a treatment that works well in other types of patients, we thought we might be able to improve things. In the past we've tended to have small studies in kidney disease, and they just simply been confusing, what we've got now with SHARP, is a really reliable, very large study with very clear results.

QS: How was The SHARP study undertaken?

Colin Baigent: The Study was organised by a team at the University of Oxford, working together with teams in seven other regions around the world. And the study was guided by an international steering committee. It consisted of some of the most eminent specialists around the world.

Kidney patients are quite hard to study because in its most severe form, kidney disease actually quite rare. So, in order to gather together over 9000 patients, we had to get the collaboration of about 400 hospitals in 18 countries. That was a major effort. And so it's very difficult to do these types of studies. We had to have the wholehearted collaboration, of not only over 1000 nurses and doctors who actually worked on the study, but also 9000 patients who after all had to take their tablets religiously every day, and had to come to study clinics without missing any. We had to ask them about what happened to them over a period of five years or in many cases longer than that. So this was a fantastic collaborative effort. We couldn't have done this study without the active support to all those patients. So, I would like to thank patients for being involved in this study, not only will it help some of them, but will also help many many future patients.

QS: What were the main fidnings?

Colin Baigent: Well, the main finding of chart was that treatment works. What we found was that if patients take their treatment over a period of about five years, and they reduce their risk of a heart attack or stroke by about one quarter. And what this means is if 1000 dialysis patients take the treatment for five years, then 40 of those 1000 patients will avoid a heart attack or stroke.

If you have slightly less severe kidney disease, then about 30 out of every 1000 would avoid a heart attack or stroke, but in both cases the benefits are substantial. There are no side effects that we could find. We were concerned, there might be an increased risk of muscle problems or liver problems, and even been suggested that one of the study drugs might cause cancer, but we found no such problems. This treatment was very safe. This is a positive result. This is a result that tells us that lowering cholesterol substantially in patients with chronic kidney disease produces real benefits. These are large benefits so we'll have a major impact on the management of kidney patients worldwide.

QS: I am a kidney patient. What should I do now?

Colin Baigent: The message for kidney patients is that they should be seeing their own kidney doctor, discuss whether this result is relevant to them. In many cases, it will be and patients all around the world, will be starting cholesterol lowering treatment as a result of these findings.

QS: What does the future hold?

Colin Baigent: We're very excited about the future we think that this is a new era in the study of kidney disease, we can take the success of these findings, build on them, and really do our best for trying to improve the health of kidney patients.

This is something that may well affect their lives in the future. We now know that cholesterol lowering treatment is beneficial for people with kidney disease, we didn't know that before. And so it's very important result.

QS: What was so good about working on SHARP?

Colin Baigent: Everybody in the SHARP team is extremely proud of these findings. It shows us that by working together, by recruiting really large numbers of patients, by working together as a team worldwide, we can actually answer some of the very difficult questions in the management of kidney patients, and I've been working on this study really since 1995 so almost 15 years, and it's so nice to get a clear result at the end of all that. It's so nice to have been able to work with so many great doctors and so many great nurses and actually to have a chance to put something back for kidney patients.

 

SHARP results

The Study of Heart and Renal Protection (SHARP) concluded that around a quarter of all heart attacks, strokes, and operations to open blocked arteries could be avoided in people with chronic kidney disease by using the combination of ezetimibe and simvastatin to lower blood cholesterol levels.

The world's largest trial investigating the benefits of cholesterol lowering in kidney patients

Comments from the Principal Investigators:

Professor Colin Baigent

This is excellent news for patients who have kidney disease. It was already known that cholesterol-lowering could reduce the risk of heart attacks, strokes and the need for surgery to unblock arteries in people with normal kidney function. But, this trial now shows that cholesterol-lowering has similar effects in people with chronic kidney disease. Taking ezetimibe plus simvastatin long-term would avoid around one quarter of heart attacks, strokes and operations to unblock arteries, leading to their prevention in at least 250,000 people with kidney disease worldwide each year.

Dr Martin Landray

In SHARP there was no evidence of any serious adverse effects and, in particular, no support for earlier concerns that ezetimibe might cause cancer. SHARP shows clearly that the large cholesterol reduction produced with this treatment is safe, and provides similar benefits to those seen in people with normal kidney function.

Summary of major findings

 

  • Taking the combination of ezetimibe and simvastatin long-term reduced the risk of heart attacks, strokes and operations to open blocked arteries by about one quarter in people with chronic kidney disease, irrespective of the severity of their disease
  • This combination treatment reduced risk safely, and may be particularly good for kidney patients as it avoids the possibility of side-effects with high statin doses
  • There was no support for previous concerns with ezetimibe about possible adverse effects on cancer, and no evidence of an increased risk of muscle or liver problems
  • This podcast presents the research done by Professor Colin Baigent whilst working in the Nuffield Department of Medicine. Professor Baigent now works at the Nuffield Department of Population Health.