Good News for Kidney Patients: World's Largest Kidney Disease Trial Shows Big Benefits From Reducing Cholesterol

By Clinical Trial Service Unit At Oxford University, PRNE
Friday, November 19, 2010

DENVER, November 20, 2010 - 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. That's the conclusion from the world's largest ever randomized trial
in kidney disease.

Unveiling the key findings today (Saturday 20 November) at the American
Society of Nephrology, the trial's principal investigator Professor Colin
said: "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, irrespective of
the severity of their illness. 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."

The Study of Heart and Renal Protection (SHARP) involved almost 9,500
volunteers aged 40 or over with chronic kidney disease recruited from 380
hospitals in 18 countries. Patients included in the trial had lost at least
50% of their normal kidney function, with a third of them requiring dialysis
treatment. None had had a previous heart attack or needed bypass surgery or
"stents" to unblock their heart arteries. Volunteers in this double-blind
placebo-controlled trial 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. Study
treatment and follow-up continued for an average of 5 years.

SHARP was designed, conducted and analysed independently of all funding
sources by the Clinical Trial Service Unit and Epidemiological Studies Unit
(CTSU) of Oxford University, with guidance by an independent Steering
Committee that included many of the world's leading kidney specialists. The
study was supported by Merck & Co., (which is known as MSD outside the U.S.
and Canada) who also supplied the study treatments, with additional support
from the Australian National Health and Medical Research Council (NHMRC), the
British Heart Foundation (BHF) and the UK Medical Research Council (MRC).
Planning began in the mid-1990s, with two pilot studies followed by a main
study that started in 2003 and ended in September of this year.

    Summary of major findings

    - The patients allocated to take ezetimibe plus simvastatin had one-sixth
      fewer heart attacks, strokes or operations to unblock arteries ("major
      atherosclerotic events"), with similar reductions observed in all
      types of patient studied.
    - During this long trial, the proportion of patients who stopped taking
      their allocated treatment was about one third, but this was not
      generally due to side-effects and was the same for both real and dummy
      treatments. If taken without interruption, however, ezetimibe plus
      simvastatin could have even larger effects than were seen in SHARP,
      potentially reducing risk by about one quarter.
    - Adding 10mg daily of ezetimibe to 20mg daily of simvastatin produced a
      large reduction in LDL ("bad") cholesterol safely. This combination
      treatment 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.

Professor Baigent said: "We knew from previous trials that statins reduce
the risk of heart attacks and strokes in people with normal kidney function.
But 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. SHARP now
provides the first direct evidence that cholesterol-lowering is indeed
effective in kidney patients, and that the benefits are substantial."

SHARP co-principal investigator, Dr Martin Landray said that SHARP
provides reassuring evidence about the safety of the ezetimibe and
simvastatin combination: "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."

The SHARP results are also relevant to people who don't have chronic
kidney disease. The combination of ezetimibe and a statin produced similar
benefits to those resulting from the same LDL cholesterol reduction achieved
with a high dose of a statin. Since the lower the cholesterol the bigger the
risk reduction, these results suggest that patients who remain at high risk
of major atherosclerotic events despite maximal statin therapy may benefit
further from adding ezetimibe to their current statin regimen.

Chronic kidney disease affects about one in 10 people worldwide. People
with chronic kidney disease tend to have a very high risk of developing heart
disease or experiencing a stroke. Until now, it has not been known how to
prevent these conditions in such patients. Consequently, it is likely that
the SHARP results will result in cholesterol-lowering treatment being used
widely in this large group of high-risk people who were previously not being
given such treatment.


NEWS TELECONFERENCE 10.45AM MT (Denver) Saturday 20th November 2010. This
news conference will last no longer than 40 minutes. This is almost
immediately after, and in addition to, the news conference being organised by
ASN in the morning.

In order to join this conference call, all participants will be required
to provide the following conference ID # 25065869

Operator assisted toll-free US dial-in number (888) 260-6134

Operator assisted INTERNATIONAL dial-in number (706) 643-1635

A recording of the conference will be available for replay two hours
after the call's completion: Dial in US (800) 642-1687 or INTERNATIONAL
(706) 645-9291

American Society of Nephrology (ASN) Renal Week

ASN Renal Week 2010, the largest nephrology meeting of its kind, provides
a forum for 13,000 professionals to discuss the latest findings in renal
research and engage in educational sessions related to advances in the care
of patients with kidney and related disorders. Founded in 1966, the American
Society of Nephrology (ASN) is the world's largest professional society
devoted to the study of kidney disease. Comprised of 11,000 physicians and
scientists, ASN continues to promote expert patient care, to advance medical
research, and to educate the renal community. ASN also informs policymakers
about issues of importance to kidney doctors and their patients. ASN funds
research, and through its world-renowned meetings and first-class
publications, disseminates information and educational tools that empower

For further information please contact: Andrew Trehearne: +44(0)789-404-2600 or Andrew.trehearne at, Please note that I will be in Denver from late afternoon, Wednesday 17 November - Sunday 21 November

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