Orlando, FL - Confirmation
that AstraZeneca's new statin, rosuvastatin (Crestorｪ),
lowers LDL cholesterol more effectively than other statins
including atorvastatin (Lipitorｨ - Pfizer), has come
from presentation of Phase III data on the drug. In addition,
for the same level of LDL lowering as atorvastatin, rosuvastatin
seems to raise HDL levels more. The studies also showed that
a great many more patients reached their target LDL levels
with rosuvastatin than with the other drugs.
Presenting the data at a press conference during the American
College of Cardiology 50th Annual Scientific Session,
Dr Evan Stein (Metabolic and Atherosclerosis Research
Center, Cincinnati, OH) said he believed one of the best advantages
of rosuvastatin was a good level of LDL lowering even at the
starting dose. "Atorvastatin lowers LDL one level more than
the other statins at its starting dose, but rosuvastatin goes
another level better again. Many doctors put their patients
on a statin but then never increase the dose. At least if
this happens with rosuvastatin, the patient will still get
a decent level of cholesterol-lowering."
Stein also said that rosuvastatin should be particularly useful
in patients with familial hypercholesterolemia (FH), who have
very high LDL levels and generally do not reach target levels
even with top doses of atorvastatin, the most potent statin
for LDL lowering currently available: "At the moment atorvastatin
is the best we've got; it can produce a 55% reduction in LDL
at its highest doses. Simvastatin comes in second with a 48%
reduction at its top dose. However, top doses of rosuvastatin
have shown an impressive 65% reduction in LDL."
Stein said rosuvastatin had a different structure at the end
of the molecule compared with other statins, which enabled
it to bind more tightly to the HMG CoA reductase enzyme, and
this probably accounted for its more potent effects.
Gorilla statin
Rosuvastatin, which has been previously dubbed "superstatin,"
was referred to at the press conference as "gorilla statin."
AstraZeneca is planning to file approval applications for
the drug in the US and Europe this summer, so it should be
on the market sometime next year. Although it does have the
best lipid-lowering profile of any statin yet, it does not
have any clinical endpoint studies, which could hamper its
use somewhat. However, this did not stand in the way of atorvastatin
when it was first launched.
Whatever its profile, rosuvastatin has a long way to go to
catch its competitors. Atorvastatin and simvastatin
(Zocorｨ - Merck) are two of the best selling drugs in the
world, both having sales of more than $5 billion.
The Phase III data was first reported on theheart.org in January,
but more details were given at the ACC meeting.
Stein reported a study in 622 FH patients who were randomized
to either atorvastatin or rosuvastatin. Both drugs were started
at 20 mg and titrated up to 80 mg.
Stein FH study - 18-week results
Endpoint
Atorvastatin
Rosuvastatin
LDL reduction
50%
58%
HDL increase
3%
12%
% of patients achieving
LDL < 100 mg/dL
3%
24%
Stein said he was particularly impressed
with the numbers reaching treatment goals on rosuvastatin. "To
get one quarter of patients down to treatment goals on a single
therapy is a real achievement. Normally we would need three
drugs for this."
In two other studies reported, rosuvastatin showed greater benefits
on lowering LDL than pravastatin, simvastatin and atorvastain
in non-FH patients. In the first of these, led by Dr Rodolfo
Paoletti (University of Milan, Milan, Italy), 502 patients
were randomized to rosuvastatin 5 mg or 10 mg, simvastatin 20
mg, or pravastatin 20 mg.
Paoletti study - 12 week results
Endpoint
Pravastatin 20 mg
Simvastatin 20 mg
Rosuvastatin 5 mg
Rosuvastatin 10 mg
LDL reduction
27%
37%
42%
48%
HDL increase
4.4%
3.9%
6.2%
6.8%
% of patients achieving
LDL <100 mg/dL
7%
20%
41%
65%
In the other study by Dr Michael
Davidson (Chicago Center for Clinical Research) and colleagues,
516 patients were randomized to rosuvastatin 5 mg or 10 mg,
atorvastatin 10 mg or placebo.
Davidson study - 12-week results
Endpoint
Placebo
Atorvastatin 10 mg
Rosuvastatin 5 mg
Rosuvastatin 10 mg
LDL reduction
0%
35%
40%
43%
HDL increase
3.8%
8.0%
12.5%
11.7%
% of patients achieving
LDL <100 mg/dL
0%
20%
42%
47%
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click on the slide logo below
Sue
Hughes
sue@conceptis.com
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