Download Table 1 . Percent Reduction in LDL-c with Statins

Table 1 . Percent Reduction in LDL-c with Statins
Statin dose per
day
Atorvastatin
10 mg
20 mg
40 mg
80 mg
Fluvastatin
20 mg
40 mg
80 mg
80 mg XL*
Lovastatin
10 mg
20 mg
40 mg
80 mg
Pravastatin
10 mg
20 mg
40 mg
80 mg*
Rosuvastatin
5 mg
10 mg
20 mg
40 mg
Simvastatin
10 mg
20 mg
40 mg
80 mg
Range of percent LDL-c
lowering from comparative
clinical Trials
Mean percent LDL-c lowering from
manufacturers prescribing information
(and from ATP-III3 if available)
Number of
clinical
trials**
28.9%–40.2%
38.4%–46.1%
45.1%–51.3%
46.3%–54%
39% (37%)
43%
50%
60% (57%)
22
8
5
6
17%–21.8%
22%–26%
29.6%–30.6%+
--
22% (18%) β
25% β
36% (31%)++ β
35% β
5
6
2
0
21.6%–24%
21%–29%
27.9%–33%
39%–48%
21%
27% (24%)
31%
42% (40%) α
2
8
5
2
18%–24.5%
23%–29%
25.2%–34%
--
22%
32% (24%)
34%
37% (34%)
9
11
8
0
39.1%–46%
37.1%–50.6%
45.7%–52.4%
53.6%–58.8%
45%
52%
55%
63%
6
9
3
3
26%–33.1%
18.5%–40%
34.3%–43%
43%–48.8%
30%
38% (35%)
41%
47% (46%)
17
17
7
5
*Newly-approved dose or dosage form with no head-to-head clinical trial data against another statin.
**% LDL-c reduction in clinical trials included in table only if data provided for a specific dosage and not
a mean dosage; total number of clinical trials will be more than the number of included trials because
some trials studied more than two statins.
+ Given as fluvastatin 80 mg qd or 40 mg bid (does not include XL product)
++ Given as fluvastatin 40 mg bid
α Given as lovastatin 40 mg bid
β Median percent change
© 2001-2008 by Oregon Health & Science University, Portland, Oregon 97201. All rights reserved.
Table 2 . Doses of statins that result in similar percent reductions in LDL-c*
Atorvastatin
-10 mg
20 mg
40 mg
80 mg
--
Fluvastatin
40 mg
80 mg
-----
Lovastatin
20 mg
40 or 80 mg
80 mg
----
Pravastatin
20 mg
40 mg
80 mg
----
Rosuvastatin
--5 or 10 mg
-20 mg
40 mg
Simvastatin
10 mg
20 mg
40 mg
80 mg
---
*estimates based on results of head-to-head trials (Evidence Table 1)
© 2001-2008 by Oregon Health & Science University, Portland, Oregon 97201. All rights reserved.
Pagina 1 di 4
Key Question
Level of Evidence
Conclusion
1. How do statins compare in their
ability to reduce LDL-c?
Fair.
The ideal study would be a doubleblind, intention-to-treat randomized
trial in which equipotent doses of
different statins were compared
with regard to LDL-lowering,
withdrawals, and adverse effects.
No studies met these stringent
criteria.
a. Are there doses for each statin
that produce similar percent
reduction in LDL-c between
statins?
Fair-to-good
Results of a large number of trials
are generally consistent with
information from the manufacturer.
When statins are provided in doses
that are approximately equipotent,
a similar percent reduction in LDLc can be achieved
b. Is there a difference in the
ability of a statin to achieve
National Cholesterol Education
Program (NCEP) goals?
Good for most comparisons (see
text).
For patients who require LDL-c
reductions of up to 35% to meet
their goal, any of the statins are
effective. In patients requiring an
LDL-c reduction of 35% to 50% to
meet the NCEP goal, atorvastatin
20 mg or more, lovastatin 80 mg,
rosuvastatin 10 mg or more, and
simvastatin 20 mg or more daily
are likely to meet the goal.
Atorvastatin 80 mg daily and
rosuvastatin 20 mg or more can
reduce LDL-C by 50% or more.
Based on fair-quality studies,
atorvastatin 80 mg daily resulted in
5 to 6 additional percentage points
of LDL reduction than simvastatin
80 mg (53%-54% vs. 47%-48%),
but had significantly higher rates of
some adverse events.
In short-term (6 weeks) studies
rosuvastatin 40 mg had greater
reduction in LDL-c than
atorvastatin 80 mg with similar
frequency of adverse events.
2. How do statins compare in their
ability to raise HDL-c?
Fair-to-good
When statins are provided in doses
that are approximately equipotent,
a similar percent increase in HDL-c
can be achieved.
There is conflicting evidence about
simvastatin vs atorvastatin, with
some studies finding no difference
and others finding simvastatin
superior. Some studies found
greater increases in HDL-c with
rosuvastatin compared with
atorvastatin, while other studies
found no difference.
3. How do statins compare in their
ability to reduce the risk of
nonfatal myocardial infarction,
angina, CHD mortality, all-cause
mortality, stroke or need for
revascularization (coronary artery
bypass graft, angioplasty or
stenting)?
NA
There are no controlled trials
comparing equivalent doses of two
or more statins to reduce the risk
of coronary events, stroke, or
death.
Pagina 2 di 4
Key Question
Level of Evidence
Conclusion
Which statins have been shown to
reduce all-cause mortality?
Good.
Patients who have never had
CHD: pravastatin (high-risk
patients), simvastatin (mixed
populations)
Patients with CHD: atorvastatin
(post-MI), pravastatin, simvastatin.
Which statins have been shown to
reduce cardiovascular mortality?
Good.
Patients who have never had
CHD: Pravastatin, simvastatin
Patients with CHD: simvastatin,
atorvastatin
Which statins have been shown to
reduce CHD events?
Fair-to-good.
Patients who have never had
CHD: atorvastatin (high-risk
patients, patients with diabetes),
lovastatin (average-risk patients),
pravastatin (high-risk patients),
simvastatin (mixed populations)
Patients with CHD: atorvastatin,
simvastatin, pravastatin.
Patients after PTCA: fluvastatin,
pravastatin.
Which statins have been shown to
reduce strokes?
Good.
Atorvastatin, pravastatin,
simvastatin
Patients with diabetes
Good
There are good efficacy data for
people with diabetes. Atorva 10
mg reduced cardiovascular events
in a primary prevention trial of
patients with diabetes (CARDS),
and simvastatin 40 mg reduced
cardiovascular events in patients
with diabetes (HPS). In a
subgroup analysis of the LIPS trial
there was a reduction in coronary
events (cardiac death, nonfatal MI,
CABG, or repeat PCI) with
fluvastatatin 80 mg in patients with
diabetes who had undergone
successful PCI. Studies that
included people with diabetes had
rates of adverse effects similar to
other studies.
4.a. Are there differences in
effectiveness of statins in different
demographic groups (age, sex,
race)?
Good (elderly, women) Poor
(African Americans, Hispanics, and
other ethnic groups)
The benefits of statins have been
documented in women and the
elderly. There are almost no data
about African Americans,
Hispanics, or other ethnic groups.
There are no data from clinical
trials comparing the efficacy of
different statins in women, the
elderly, or African Americans
4.b. Are there differences in safety
of statins in different demographic
groups (age, sex, race)?
Poor
There are no data from clinical
trials comparing the safety of
different statins in women, the
elderly, or African Americans.
A pharmacokinetic study of
rosuvastatin conducted in the US
demonstrated an approximate
2-fold elevation in median
exposure in Asian subjects (having
either Filipino, Chinese, Japanese,
Korean, Vietnamese, or AsianIndian origin) compared with a
Caucasian control group.
Pagina 3 di 4
Key Question
Level of Evidence
Conclusion
a. General population
Good
Although CPK elevations are common, the risk of
symptomatic myopathy is low. All of the available statins
(simvastatin, lovastatin, atorvastatin, fluvastatin, pravastatin,
rosuvastatin), when administered alone, have been
associated with infrequent myotoxic adverse effects ranging
from myalgia, and myopathy to rhabdomyolysis.
Two meta-analyses of clinical trials found rates of elevated
transaminases (liver function tests) to be no higher among
patients taking statins than among those receiving placebo.
There is no evidence that elevated transaminases
associated with statin use increase the risk of clinically
significant liver failure. In a trial of two doses of atorvastatin,
the incidence of persistent elevations in liver
aminotransferase levels 2 per 1000 in patients taking
atorvastatin 10 mg daily, versus 1.2 per 1000 in patients
taking 80 mg daily.
There is insufficient evidence to determine which statin or
statins are safer with regard to muscle toxicity or elevated
liver enzymes.
Among high potency statins, at doses below 80 mg, rates of
adverse events and withdrawals due to adverse events were
similar in patients taking atorvastatin or simvastatin.
Atorvastatin 80 mg had a higher rate of some adverse
effects (GI disturbances and transaminase elevation) than
simvastatin 80 mg daily in a trial in which the LDL lowering
of atorvastatin was greater than that of simvastatin.
Adverse event rates in patients using rosuvastatin 40 mg
were similar to rates in patients using atorvastatin 80 mg in
short-term trials.
b. Special populations: Patients with
diabetes
Good
Studies that included people with diabetes had rates of
adverse effects similar to other studies.
Patients with HIV and transplant
patients
One fair-quality
observational study; one
small trial (pravastatin) case
reports; expert opinion;
pharmacology.
In theory, pravastatin, fluvastatin, and rosuvastatin have the
lowest potential for interactions with drugs that are potent
inhibitors of CYP 3A4.
Atorvastatin, lovastatin and simvastatin have the greatest
potential for clinically important interactions.
Fluvastatin has a potential for interaction with drugs
inhibiting CYP 2C9 (Table 12) and pravastatin has the
lowest potential for drug interactions and is the safest choice
in those patients receiving potent CYP inhibitors.
Experts recommend starting with pravastatin and fluvastatin
and using the lowest dose possible. Although there is no
proof from clinical studies that these recommendations are
correct, on ethical grounds low-dose pravastatin and
fluvastatin probably cannot be tested in a good-quality
controlled study against high doses or other statins.
Drug interactions
Fair
The combination of any statin with fibrates, and to a lesser
extent niacin, can result in a higher risk for myopathy or
rhabdomyolysis.
5. Are there differences in the safety
of statins?
© 2001-2008 by Oregon Health & Science University, Portland, Oregon 97201. All rights reserved.
Pagina 4 di 4