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UPDATE ON STATIONS: FOCUS
ON UNAPPROVED USES

Jose L. Barboza Jr, Pharm.D. Candidate


Over two decades ago, the first HMG-CoA re-
ductase inhibitor station ) was approved to
treat hypercholesterolemia, a major modifi-
able risk factor for cardiovascular disease. Since
then, both the number of stations approved, and indi-
cations for their use have increased. In addition to
hypercholesterolemia, indications now include pre-
venting and slowing the progression of atherosclero-
sis in primary and secondary cardiovascular events
and coronary artery disease as well as use in Het-
erozygous Familial Hypercholesterolemia (HeFH) in
adolescents. The six currently marketed stations are
listed in Table 1.


Table 1. Currently Marketed Statins

DRUG TRADENAME APPROVAL DATE
Lovastatin Mevacor September, 1987
Pravastatin Pravachol October, 1991
Simvastatin Zocor December, 1991
Fluvastatin LescolO December, 1993
Atorvastatin Lipitor December, 1996
Rosuvastatin Crestor August, 2003


Over the last two decades, stations have become
one of the most frequently prescribed drug classes
among all medications. In 1992, stations accounted
for 47% of all lipid lowering medications, growing to
87% in 2002.7 Lipitor has been the number 1 sell-
ing drug in the US this decade. In 2007, it accounted
for $6.165 billion in US sales, despite a 6.3% reduc-
tion in sales compared with 2006. Crestor had
$1.367 billion US sales in 2007, an increase of
29.2% from 2006.8
Although stations have been commonly used for
cholesterol lowering and prevention of cardiovascu-
lar disease, there is an increasing amount of attention
directed towards potential new benefits of station ther-
apy. This article will evaluate the data on station use
for unapproved indications, including prevention of
cardiovascular events in patients with high C-
Reactive Protein (CRP) and Low Density Lipopro-
tein Cholesterol (LDL-C), prevention of venous
thromboembolism, station use in children, and use in
rheumatoid arthritis. The pharmacology, clinically
useful pharmacokinetics, most prevalent side effects,
and prescription costs of the stations will also be cov-
ered.






INSIDE THIS ISSUE:
UPDATE ON STATIONS:
Focus ON UNAPPROVED USES




li ^ ^ ^ ^^ ^ ^ r


mm


PharmaNote


VOLUME 24, ISSUE 9 JUNE 2009
i ^ ^ ^ ^^ ^ ^ ^ ^ ^^ ^ ^ ^ ^^ ^ ^ ^i^^ ^ ^ ^ j


Volume 24, Issue 9 1 June 2009


PharmaNote








Table 2. Pharmacokinetic Overview of Available Statins

FACTOR ATORVASTATIN5 FLUVASTATIN4 LOVASTATIN1 PRAVASTATIN2 ROSUVASTATIN6 SIMVASTATIN3


Absorption (%)

Food Effect on Absorption (%)

Bioavailability (%)

t-max (hrs)

Protein Binding (%)

Metabolizing Enzyme

Possible Drug Interactionst

Increase Statin Levels
















Decrease Statin Levels


99+

not affected


14

1.0-2.0

>98

CYP3A4


Itraconazole,
Clarithromycin,
Erythromycin,
Cyclosporine,
HIV Protease
Inhibitors,
Diltiazem,
Grapefruit Juice,
Oral Contraceptives






Colestipol
Antacids
Rifampin
efavirenz
Digoxin
Penytoin
St. John's Wort


24

0.5-1

98

CYP2C9


Cyclosporine,
Gemfibrozil, Niacin
Erythromycin,
Fluconazole,
Diclofenac,
Cimetidine,
Ranitidine,
Omeprazole








Cholestyramine
Phenytoin
Rifampicin


30

Increased

<5

2

>95

CYP3A4


Itraconazole,
Clarithromycin,
Erythromycin,
Ketoconazole,
Nefazodone,
HIV Protease
Inhibitors,
Cyclosporine,
Amiodarone,
Verapamil,
Gemfibrozi,
Niacin (1 g/day),
grapefruit juice (>1
quart daily)
Rifampin
Phenytoin
St. John's Wort


34

Decreased

17

1-1.5

50

Minimal CYP



Cyclosporine,
Erythromycin,
Itraconazole,
Gemfibrozil,
Niacin











Cholestyramine
Colestipol


40-60


not affected

20

3.0-5.0

88

Minimal CYP


Cyclosporine
Lopinavir/ Ritonavir,
Nevazodone,
Clarithromycin,
Gemfibrozil,
Niacin










Antacids
St. John's Wort


<5

1.3-2.4

95

CYP3A4


Cyclosporine,
Itraconazole,
Ketoconazole,
Erythromycin,
Clarithromycin,
Nefazodone,
HIV Protease
Inhibitors,
Amiodarone,
Gemfibrozil,
Verapamil,




Digoxin
St. John's Wort


Prodrug

t1/2 (hrs)
Renal Clearance (%)


Adjustments in Renal failure


No dose adjustment
necessary.


No dose adjustment
necessary. No data
available for 40mg in
severe renal impair-
ment


Severe renal insuffi-
ciency, CrCI <30 mL/
min, use caution and
carefully consider any
dose above 20 mg/day


Closely monitor pa-
tients with renal im-
pairment


Severe renal insuffi-
ciency, CrCI <30 mL/
min). not on hemodi-
alysis, dosing should
be started at 5 mg/day


Severe renal impair-
ment, dosing should
be started at 5 mg/day
and be closely moni-
tored


t/2 = half-life; CrCI = creatinine clearance; CYP = Cytochrome P450.
t Statins can potentiate the effects of warfarin


Yes
1.1-1.7
10


No
1.3-2.8
20







UNAPPROVED USES


Statins inhibit 3-Hydroxy-3-methyl-glutaryl-CoA
(HMG-CoA) reductase, the rate limiting enzyme in
cholesterol biosynthesis. Reduction of cholesterol
biosynthesis decreases intracellular cholesterol pools
in the hepatocyte, thus upregulating low-density lipo-
protein (LDL) receptors. These LDL receptors re-
move LDL, intermediate-density lipoprotein (IDL)
and very-low-density lipoprotein (VLDL) from the
systemic circulation.9
LDL causes the upregulation of monocyte
chemotactic protein (MCP-1) which recruits mono-
cytes to the endothelium. These monocytes subse-
quently differentiate into macrophages which are in-
flammatory due to cytokine secretion. Foam cells,
which are derived from accumulation of macro-
phages, are metabolically active and can secrete
growth factors and metaloproteinases which can
eventually result in ACS and coronary disease. The
accumulation of foam cells over time leads to athero-
sclerosis as well as the development of coronary le-
sions. As these lesions increase, the potential for
ischemia also increases due to diminished blood flow
to the tissues. Alternatively, the lesions may rupture
and trigger an acute coronary event.
The variable damaging mechanisms of increased
LDL explain the pleiotropic effects of LDL lowering
statins.10

PHARMACOKINETICS

Pharmacokinetic differences between stations al-
low clinicians to customize therapy using patient-
specific factors to promote optimal response while
minimizing adverse effects. When selecting a station,
the patient's renal function should be assessed to de-
termine whether a renally-eliminated station is an ap-
propriate choice. Hepatically-eliminated stations may
undergo metabolism by varying enzymes; therefore,
the patient's medications should also be taken into
account due to possible drug-drug interactions. Cer-
tain stations are affected by food, with lovastatin rec-
ommended to be taken with evening meals to in-
crease its absorption. Table 2 outlines the significant
pharmacokinetic profile for each station. Common
drug interactions which affect station levels are listed,
but this list is not all-inclusive. It should be noted
that all stations are classified as pregnancy category X.


Prevention of Cardiovascular Events in Patients
with high CRP and low LDL
Although prevention of cardiovascular events in
patients with hyperlipidemia, cardiovascular disease,
and diabetes is an established and approved indica-
tion for stations, half of all myocardial infarctions and
strokes occur in men and women in whom stations are
not indicated. Consequently, it has been suggested
that other biomarkers may exist that could more ac-
curately distinguish those who would benefit from
preventative therapy. One potential inflammatory
marker filling this role is C-reactive protein (CRP).
Previous studies demonstrate a relationship between
CRP and future vascular events regardless of LDL
levels.11, 12 Statins reduce CRP, and by reducing
CRP levels they may reduce cardiovascular events.13
The Rosuvastatin to Prevent Vascular Events in Men
and Women with Elevated C-Reactive Protein trial
was a randomized, double-blind, placebo controlled,
multicenter trial evaluating the effects of rosuvastatin
on the rate of first major cardiovascular events in
men and women who did not have hyperlipidemia
but had elevated C-Reactive Protein (CRP) levels.14
The trial's primary objective was the Justification for
the Use of Statins in Prevention: an Intervention
Trial Evaluating Rosuvastatin (JUPITER).
The primary endpoint was the occurrence of the
first cardiovascular event, defined as nonfatal myo-
cardial infarction, nonfatal stroke, hospitalization
from unstable angina, arterial revascularization pro-
cedure, or cardiovascular mortality. Results of the
JUPITER trial are summarized in Table 3. The pri-
mary endpoint was significantly reduced in rosuvas-
tatin-treated patients with event rates of 0.77 vs. 1.36
per 100 person-years (p<0.00001) of follow-up in the
rosuvastatin and placebo groups, respectively. Sec-
ondary endpoints of all-cause mortality, myocardial
infarction, stroke, revsascularization or unstable an-
gina, and cardiovascular mortality were also signifi-
cantly reduced in the rosuvastatin group. Addition-
ally, the rates of death from any cause were de-
creased in the rosuvastatin group (1.00 vs. 1.25;
p=0.02). In summary, there was a significant reduc-
tion in the incidence of major cardiovascular events
attributed to the rosuvastatin group. It is unclear
whether these effects are related to stations as a class
or rosuvastatin only.


-U


PHARMACOLOGY


Volume 24, Issue 9 i June 2009


PharmaNote







Table 3. Summary of JUPITER Trial.14

DESIGN n INCLUSION CRITERIA SERIOUS ADVERSE EVENTS RESULTS
SRCT *Ro=8,901 -CRP > 2.0mg/L No significant differences seen Rosuvastatin significantly reduced the incidence
SDB PCB=8,901 LDL< 130 mg/dL except: of major CV events in non-hyperlipidemia patients
-.Physician reported diabe- with high CRP and reduced high sensitivity CRP by
-MC -Age (Men 50, 37%
Wmen 60) tes: 270 for the rosuvas-
Women> 60)
tatin group and 216 for the Rates of Ro vs. PCB:
.TG < 500mg/dL placebo group (P=0.01) Primary endpoint: 0.77 vs. 1.36 per 100 PYF
.1 nonfatal rhabdomyolysis (P<0.00001)
in the rosuvastatin group .MI: 0.17 vs. 0.37(p = 0.0002)
-Stroke 0.18 vs. 0.34 (p = 0.002)
RV or UA: 0.41 vs. 0.77 (p < 0.00001)
-Combined endpoint of MI, stroke, death from CV
causes: 0.45 vs. 0.85 (p < 0.00001)
Death from any cause: 1.00 vs. 1.25 (p = 0.02)
No significant incidence of myopathy or cancer

RCT = randomized controlled trial; DB = double-blind; MC = multi-center; Ro = rosuvastatin 20mg; PCB =Placebo; MI = myocardial infarction; RV = revasculariza-
tion; UA = unstable angina; PYF = person-years of follow-up; CRP = C-reactive protein; CV = cardiovascular; LDL = low-density lipoprotein cholesterol.


Venous Thromboembolism Prevention
There has been conflicting evidence associating
station use with a reduction in venous thromboem-
bolism (VTE). The mechanism by which stations can
potentially decrease VTE is not fully understood;
however, it is thought to be through inhibition of iso-
prenylation of signaling proteins as well as reduction
in tissue factor expression, thrombin generation, at-
tenuated fibrinogen cleavage, and activation of fac-
tors V and VII. A substudy of the JUPITER trial
analyzed the effects of rosuvastatin 20mg vs. placebo
on venous thromboembolism or pulmonary embo-
lism in men and women who, at the time of the trial,
had no indications to be on station therapy (See table 2
for specifics of the trial).15 There were 34 throm-
boembolic events in the rosuvastatin arm compared
to 60 in the placebo arm. This accounts for rates of
0.18 vs. 0.32 events per 100 person-years for the ro-
suvastatin and placebo groups, respectively
(p=0.007). For provoked and unprovoked venous
thromboembolisms, the rates for deep-vein thrombo-
sis rates were 0.09 vs. 0.20 per 100 patient years
(p=0.004) and 0.09 vs. 0.12 (p=0.42), respectively.
In summary, there was a significant reduction in the
incidence of venous thromboembolism. Other stud-
ies are needed to confirm these findings in addition
to clarifying the mechanism and evaluating station use


in high risk patients. The authors did not suggest
whether these effects were related to stations as a class
or rosuvastatin in particular.15

Use in Children
There is controversy in the prescribing of stations
to children, with concern for both the adverse event
profile, including the stunting of growth, as well as
with critics who state that the main focus in this
population should be on lifestyle changes rather than
drug therapy. Statins are currently approved in chil-
dren > 10 years of age (in > 8 for pravastatin) who
have HeFH, a genetic disorder in which one or both
strands of DNA responsible for LDL receptor protein
are altered, subsequently causing increased LDL lev-
els. Current evidence correlates childhood choles-
terol levels to fatty streak formation and to an ele-
vated incidence of coronary heart disease in adult-
hood; therefore, stations may benefit children who
have high cholesterol regardless of familial hyper-
cholesterolemia.16
Jongh and colleagues, in a multicenter, random-
ized, double blind, placebo-controlled study evalu-
ated 173 children with HeFH over 48 weeks.17 The
study found that simvastatin was well tolerated with
no deleterious effects on growth and pubertal devel-
opment, as well as beneficial modified lipid/


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Volume 24, Issue 9 1 June 2009


PharmaNote







lipoprotein profiles in children. Compared to pla-
cebo, there was a significant reduction in total cho-
lesterol, LDL, and apoB levels. Simvastatin 40mg
did not have clinically meaningful effects on gonadal
function in children and adolescent boys or girls nor
did it affect normal growth. With the exception of
decreases in dehydroepiandosterone, significant
changes from baseline in adrenal, gonadal, and pitui-
tary hormones were not found in either group. There
were no cases of myopathy, and no significant differ-
ences were observed between the treatment groups
regarding the number of clinical and laboratory AEs,
drug related AEs, or clinically meaningful elevations
in hepatic transaminases (ALT and AST) and
creatine phosphokinase. This study demonstrated the
safety and efficacy of simvastatin < 40 mg/day in
children aged 10 to 17 years.17
Avis and colleagues performed a meta-analysis
of randomized, double-blind, placebo controlled tri-
als that evaluated station therapy in children aged 8 to
18 years with HeFH.18 The analysis included 6 trials
accounting for 798 children and the length of treat-
ment varied between 12 to 104 weeks. Significant
reductions were noted among levels of total choles-
terol, LDL cholesterol, and apolipoprotein B,
whereas HDL and apolipoprotein Al levels were in-
creased. With respect to the adverse effect profile,
including sexual development, liver toxicity, or mus-
cle toxicity, there were no statistically significant
differences found between station and placebo treated


children. In summary, the study suggests that station
treatment may be considered for all children aged 8
to 18 with HeFH due to both the safety and efficacy
of station treatment.18
McCrindle and colleagues, in a multicenter, ran-
domized, double-blinded, placebo controlled trial
evaluated the safety and efficacy of atorvastatin 10-
20 mg in decreasing LDL-C in patients with FH.19
The patients were 10 to 17 years old with FH or se-
vere hyperlipidemia, defined as LDL-C > 190mg/dL
or > 160mg/dL with positive family history or docu-
mented premature cardiovascular disease in a 1st or
2nd degree relative. All patients who completed the
double blind phase were eligible to continue treat-
ment for 26 more weeks in an open label atorvastatin
10mg study. Overall, no clinically significant in-
creases in the incidence or severity of treatment ad-
verse events were observed in the station groups com-
pared to placebo. None of the patients discontinued
treatment as a result of increased ALT or AST. In
summary, there were significant reductions in LDL-
C, TC, TG, apolipoprotein B, and increased HDL-C
in the atorvastatin group. The study showed safety
and efficacy in the treatment of elevated lipid levels
in children and adolescents with known FH or severe
hypercholesterolemia.19
Although evidence supports the safety and effi-
cacy of stations in children aged > 8 years, the topic
remains controversial with many clinicians prefer-
ring lifestyle changes over drug therapy.


Table 4: Studies Evaluating Rheumatoid Arthritis and Statins.
INCLUSION STUDY
STUDY DESIGN n RESULTS
CRITERIA LENGTH
Okamoto, Single 7,512 enrolled RA diagnosis Cross Statin vs. non-statin patients showed:
et al. institute, Analyzed cross -Pt age 18-65 sectional -Lower C-reactive protein (0.85 vs 1.24 mg/
(2007)22 prospective sectional data of years data was dL) (p < 0.0001)
observational 4,152, of which -Active dis- analyzed -Lower swollen joint counts (1.80 vs 2.55) (p
cohort 279 (6.7%) took ease 0.0001)
stations More frequently used corticosteroids (avg.
dosage of 2.88 vs 2.40 mg/day) (p < 0.05)
McCarey, Randomized, 116 pts receiving -ACR criteria 6 months Atorvastatin 40mg vs. placebo:
et al. double blind, DMARD therapy for RA -DAS28 improvement (-0.5 vs. 0.03) (p =
(2003)23 placebo- received either -Symptomatic 0.004)
controlled atorvastatin(n=58) AR despite -Achieved EULAR response: (31% vs. 10%) (p
or placebo(n=58) DMARD = 0.006)
treatment -CRP: (-0.46 vs 0.12) (p < 0.0001)
SESR: (-5.03 vs. 1.91) (p = 0.005)
-SJC: (-2.69 vs. -0.53) (p = 0.0058)
RA = rheumatoid arthritis; DMARD = disease-modifying antirheumatic drug therapy; DAS28 = Disease Activity Score (http://www.das-score.nl); EULAR = European
League Against Rheumatism; CRP = C-reactive protein; ESR = erythrocyte sedimentation rate; SJC = swollen joint count; ACR = American College of Rheumatology.

Pharm~oteVolue 24 Isse 9 Jun 200


Volume 24, Issue 9 i June 2009


PharmaNote







Beneficial Uses in Rheumatoid Arthritis
Rheumatoid arthritis (RA) and atherosclerosis
have a similar pathogenesis, with inflammation being
a major causative agent.20 Both atherosclerosis and
RA are characterized by increases in T-cell, B-cell,
monocyte, and endothelial cell activations, as well as
increased CRP levels. Statins block the immunosup-
pressive and anti-inflammatory effects of the meva-
lonate pathway. They selectively inhibit leukocyte
function antigen-1 (LFA-1) mediated adhesion. The
LFA-1 is expressed on the surface of leukocytes and
binds to the intermolecular adhesion molecule 1
when activated.21 LFA-1 cells promote immunosup-
pression by co-stimulating T cells. Blocking these
two immune responses may improve rheumatoid ar-
thritis symptoms and disease course. Two studies in
particular have observed benefits with station use in
this population as shown in Table 4.22 23
Both Okamoto and McCarey observed benefits in
reduced swollen joint counts and CRP levels in those
on station therapy. However, in the case of Okamoto,
et al., station users had a higher percent of corticoster-
oid use stationn users: 62% vs. non station users:
52.5%) and higher doses; therefore, the lower disease
activity in this study could be attributed to increased


corticosteroid use. The McCarey et al. study showed
a stronger relationship between station use and RA
prevention. The atorvastatin group showed a de-
crease of 0.52 in DAS28, a decrease of 2.16 in swol-
len joint count, and a decline in CRP and ESR of
50% and 28% respectively compared to placebo.
The results in these studies show that stations could be
used to improve RA symptoms in combination with
DMARDS. Before stations can be routinely recom-
mended in RA therapy, larger, more highly powered
studies, preferably linked to one specific DMARD,
will be needed. It is unknown whether these benefits
are a class effect or applicable to specific stations
only; however, Okamoto and colleagues observed
benefits with the use of four different stations, with
pravastatin being the most prevalent at 49%.

ADVERSE EVENTS

Table 4 summarizes the most common side ef-
fects of the various commercially available stations.
Adverse effects associated with station therapy are
generally mild but can occasionally be of significant
consequence.


Table 4: Percent of Patients Experiencing Adverse Events with Currently Available Statins.
Rosuvastatin6 Atorvastatins Simvastatin3 Pravastatin2 Lovastatin1 Fluvastatin4
10mg 10mg 20-40mg 40mg 20mg 20, 40, 80mg*

Headache 5.0 (4.9) 5.4 (7.0) 2.5 (2.1) 1.9(1.8) 2.6 (2.7) 8.9 (7.8)
Abdominal Pain 1.8 (2.4) 2.8 (0.7) 5.9 (5.8) 2.4 (2.5) 2.0 (1.6) 4.9 (3.8)
Dyspepsia, Heartburn
sp sia, Har 2.3 (4.1) 4.9 (3.9) 3.5 (3.7) 1.3 (1.9) 4.9 (4.2)
or Gastritis
Diarrhea 2.7 (1.5) 3.7 (4.2) 7.9 (3.2)
Flatulence 2.1(3.3) 1.2 (1.1) 2.6 (2.3) 2.6 (2.5)
Myalgia 1.3(2.1) 3.2 (1.1) 3.7 (3.2) 1.4(1.4) 2.6 (1.7) 5.0 (4.5)
Constipation 2.4 (2.1) 2.1(1.8) 2.2 (1.6) 1.2(1.3) 2.0 (1.9)
Nausea 3.1(3.5) 1.6(1.6) 1.9 (2.5) 3.2 (2.0)
Dizziness 4.0(24) (2.8) 2.2 (2.1) 0.7 (0.7)
Rash 3.9 (0.7) 2.1(2.2) 0.8 (0.7)
Sinusitis 2.8 (2.6) 2.3 (1.8)
Arthralgia 7.1(24) (10.1) 2.0 (1.5) 6.0 (5.8)
Asthenia/Fatigue 2.6 (3.2) 2.2 (1.9) 3.4 (3.3)
The numbers inside the parenthesis "( )" are the placebo side effects seen in each study. *The Fluvastatin package insert does not specify which placebo con-
trolled trials was used. Blank cells represent categories not measured in the specific trials.
Graham et al, studied the rates of rhabdomyolisis in lipid lowering drugs and found that the incidence per 10,000 person-years of monotherapy with atorvastatin,
simvastatin, or pravastatin was 0.44.25
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Volume 24, Issue 9 i June 2009


PharmaNote







Monitoring Parameters
The National Lipid Association Statin Safety As-
sesment Task Force released their recommendations
on monitoring parameters in 2006.26
Liver function tests (LFTs) should be obtained at
baseline, and monitored 12 weeks after initiating
therapy or after a dose increase and periodically
thereafter. The National Lipid Association Statin
Safety Assessment Task force recommend that rou-
tine monitoring is not supported by the available evi-
dence and current recommendations for monitoring
need to be reconsidered by the FDA. Monitoring for
patient complaints of jaundice, malaise, fatigue, leth-
argy, and related symptoms should also be imple-
mented.
Obtaining a baseline creatinine phosphokinase
(CK) should be considered in patients who are at
high risk of muscle toxicity. The levels should be
obtained in symptomatic patients in order to help
measure the severity of muscle damage and to facili-
tate the decision about whether to continue therapy
or alter doses. CK levels should not be measured
routinely in non-high risk patients, nor should they
be measured in asymptomatic patients during the
course of station therapy.26


COSTS


Average monthly costs for currently available
prescriptions are summarized in Table 5. Generi-
cally-available stations average approximately $25/
month, whereas brand-only stations are associated
with a four-fold increase in cost.



Table 5. Monthly Costs of Available Statins.

BRAND GENERIC PRICE (#30)

Crestor 10mg Rosuvastatin $123.61

Lipitor 10mg Atorvastatin $89.99

Zocor 20mg Simvastatin $27.99 (generic)

Pravachol 40mg Pravastatin $25.99 (generic)

Mevacor 20mg Lovastatin $22.99 (generic)

Lescol 20mg Fluvastatin $94.50

Prices obtained from www.drugstore.com


SUMMARY

Statins are being studied for a variety of new in-
dications. Of these potential new indications, the
JUPITER12 study showed that rosuvastatin caused a
significant reduction in the incidence of major car-
diovascular events in patients without hyperlipide-
mia, who have high C-reactive protein. This study
also illustrates the benefits of rosuvastatin on reduc-
ing the incidence of VTE.13 Available data suggests
that stations are safe in children; however, more clini-
cal trials are needed in order to define their place and
role. Statins also appear efficacious in treating rheu-
matoid arthritis, though larger clinical trials are
needed to fully elucidate these benefits. Ongoing
studies are assessing the potential benefits of stations
in cancer and dementia prevention, cognitive func-
tion disorders, and other indications. With a few
exceptions, it is unclear whether these benefits are
attributable to stations as a class or to a particular
station.


*


REFERENCES


1. Merck & Co., Inc. MEVACOR (Lovastatin)
package insert. Whitehouse Station, NJ; 2006.
2. Bristol-Myers Squibb Co. PRAVACHOL
(Pravastatin sodium) package insert. Princeton,
NJ 08543 USA; 2007.
3. Merck & Co., Inc. ZOCOR (Simvastatin) pack-
age insert. Whitehouse Station, NJ; 2008.
4. Novartis Pharmaceuticals Corp. LESCOL
(fluvastatin sodium) package insert. East Hano-
ver, New Jersey 07936; 2006.
5. Pfizer Inc. LIPITOR (Atorvastatin calcium)
package insert. New York, NY 10017; 2006.
6. AstraZeneca Pharmaceuticals LP. CRESTOR
(Rosuvastatin) package insert. Wilmington, DE
19850; 2007.
7. Mah J, Sehgal N, Ayanian J, et al. National
trends in station use by Coronary Heart Disease
Risk Category. PLoS Medicine 2005;2(5):e123.
8. Retrieved April 18, 2009 from Drugs.com Web-
site: http://drugs.com/top200.html
9. Rosenson RS, Tangney CC. Antiatherothrom-
botic properties of stations: implications for car-
diovascular event reduction. JAMA 1998;279


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(20):1643-50.
10. Palinski W, Tsimikas S. Immunomodulatory ef-
fects of stations: mechanisms and potential impact
on arteriosclerosis. J Am Soc Nephrol 2002;13:
1673-81.
11. Pai JK, Pischon T, Ma J, et al. Inflammatory
markers and the risk of coronary heart disease in
men and women. N Engl J Med 2004;351:2599-
610.
12. Ridker PM, Hennekens CH, Buring JE, Rifai N.
C-reactive protein and other markers of inflam-
mation in the prediction of cardiovascular disease
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The PharmaNote is Published by:
The Department of Pharmacy
Services, UF Family Practice Medical
Group, Departments of Community
Health and Family Medicine and
Pharmacotherapy and Translational
Research
University of Florida


John G. Gums Editor
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Steven M. Smith Assistant Editor
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PVl 9 n
"lb~~~~~~


Volume 24, Issue 9 i June 2009


PharmaNote




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