Endocr J. 2005 Apr;52(2):259-64.
Anti-oxidative Effect of Fluvastatin in Hyperlipidemic Type 2
Diabetic Patients.
Miwa S, Watada H, Omura C, Takayanagi N, Nishiyama K, Tanaka
Y, Onuma T, Kawamori R.
Department of Medicine, Metabolism and Endocrinology, Juntendo University
School of Medicine.
An open-label prospective cross-over trial was performed to evaluate
the antioxidative effect of fluvastatin in Japanese type 2 diabetics with
hyperlipidemia. The study subjects were 10 patients who were on pravastatin
(10 mg/day) or simvastatin (5 mg/day). After at least 12 weeks of continuous
pravastatin or simvastatin therapy, the drugs were washed out for 12 weeks
and replaced with fluvastatin (30 mg/day), then the treatment was continued
for another 12 weeks. Total cholesterol and LDL cholesterol were efficiently
and comparably reduced by all three statin agents. There were no differences
in serum parameters of oxidative stress such as malondialdehyde-modified
low-density lipoprotein, thiobarbituric acid-reactive substances, and
8-iso-prostaglandin F2alpha between pravastatin/simvastatin and fluvastatin.
However, fluvastatin, but not pravastatin/simvastatin, significantly reduced
3,5,7-cholestatriene in erythrocyte membrane, representing the extent
of membrane cholesterol peroxidation. Our data demonstrated that fluvastatin
has a unique anti-oxidative effect in patients with type 2 diabetes and
hyperlipidemia, compared with other statins.
Arq Bras Cardiol. 2005 Apr;84(4):314-9. Epub 2005 May 2.
[Effects of atorvastatin, fluvastatin, pravastatin, and simvastatin
on endothelial function, lipid peroxidation, and aortic atherosclerosis
in hypercholesterolemic rabbits.]
[Article in Portuguese]
Jorge PA, Almeida EA, Ozaki MR, Jorge M, Carneiro A.
Faculdade de Ciencias Medicas, Universidade de Campinas, Campinas.
OBJECTIVE: To compare the effects of atorvastatin, fluvastatin, pravastatin,
and simvastatin on endothelial function, aortic atherosclerosis, and the
content of malondialdehyde (MDA) in native and oxidized LDL and in the
arterial wall of hypercholesterolemic rabbits after adjusting the dosages
of those statins to reduce total serum cholesterol levels to similar values.
METHODS: Male rabbits were divided into the following 6 groups of 10 animals
(n=10): 1) GH (control) - hypercholesterolemic animals; 2) GA - atorvastatin;
3) GF - fluvastatin; 4) GP - pravastatin; 5) GS - simvastatin; and 6)
GN - normal. The animals were fed a standard food preparation enriched
with 0.5% cholesterol and 2% coconut oil for 45 days. Fifteen days after
beginning the experiment, atorvastatin, fluvastatin, pravastatin and simvastatin
were administered for 15 days through gavage, and the dosages were adjusted
to obtain similar cholesterol values in each group. At the end of the
experiment, a blood sample was withdrawn for determining total cholesterol
and separating the lipoproteins, and a segment of the thoracic aorta was
removed to be used for studying endothelial function and lipid peroxidation,
and for measuring aortic atherosclerosis in histological sections. RESULTS:
The statins significantly reduced total serum cholesterol levels, LDL-cholesterol
levels, and aortic atherosclerosis. The MDA content was also significantly
reduced in native and oxidized LDL, as well as in the arterial wall. Endothelium-dependent
relaxation was significantly greater in the treated group compared with
that in the hypercholesterolemic group. CONCLUSION: The statins, at dosages
adjusted, had a significant and similar effect in reducing lipid peroxidation
in native and oxidized LDL-C and in arterial walls, in decreasing aortic
atherosclerosis, and in reverting endothelial dysfunction.
Ann Pharmacother. 2005 Mar 1.
Cost-Effectiveness of Fluvastatin Following Successful First
Percutaneous Coronary Intervention (April).
Delea TE, Jacobson TA, Serruys PW, Edelsberg JS, Oster G.
Policy Analysis Inc. (PAI), Brookline, MA.
BACKGROUND: In the LIPS (Lescol Intervention Prevention Study), fluvastatin
80 mg/day reduced the risk of major adverse cardiac events (MACE) by 22%
versus placebo (p = 0.01) following successful first percutaneous coronary
intervention (PCI) in patients with stable or unstable angina or silent
ischemia. The cost-effectiveness of such therapy is unknown. OBJECTIVE:
To evaluate the cost-effectiveness of fluvastatin following successful
first PCI from a US healthcare system perspective. METHODS: We used a
Markov model to estimate expected outcomes and costs of 2 alternative
treatment strategies following successful first PCI in patients with stable
or unstable angina or silent ischemia: (1) diet/lifestyle counseling plus
immediate fluvastatin 80 mg/day; and (2) diet/lifestyle counseling only,
with initiation of fluvastatin 80 mg/day following occurrence of future
nonfatal MACE. The model was estimated with data from LIPS and other published
sources. Cost-effectiveness was calculated as the ratio of the difference
in expected medical-care costs to the expected difference in life-years
(LYs) and quality-adjusted life-years (QALYs) alternatively. RESULTS:
Treatment with fluvastatin following successful first PCI was found to
increase life expectancy by 0.78 years (QALYs 0.68). Cost-effectiveness
of fluvastatin following successful first PCI is $13 505 per LY ($15 454
per QALY) saved. Ratios are lower for patients with diabetes ($9396 per
LY; $10 718 per QALY) and those with multivessel disease ($9662 per LY;
$11 076 per QALY). Findings were robust with respect to changes in key
model parameters and assumptions. CONCLUSIONS: Fluvastatin therapy following
PCI is cost-effective compared with other generally accepted medical interventions.
World J Gastroenterol. 2005 Feb 21;11(7):1040-3.
Inhibitory effect of fluvastatin on ileal ulcer formation in rats
induced by nonsteroidal antiinflammatory drug.
Hagiwara M, Kataoka K, Arimochi H, Kuwahara T, Nakayama H, Ohnishi
Y.
Department of Molecular Bacteriology, Graduate School of Medicine, The
University of Tokushima, Tokushima 770-8503, Japan. kataoka@basic.med.tokushima-u.ac.jp.
AIM: Nonsteroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal
damage as one of their side effects in humans and experimental animals.
Lipid peroxidation plays an important role in NSAID-induced ulceration.
The aim of this study was to investigate the inhibitory effect of 3-hydroxy-3-methylglutaryl
coenzyme A (HMG-CoA) reductase inhibitors on the ulceration in small intestines
of rats. METHODS: The effects of three HMG-CoA reductase inhibitors, fluvastatin,
pravastatin and atorvastatin on ileal ulcer formation in 5-bromo-2-(4-fluorophenyl)-3-(4-
methylsulfonylphenyl) thiophene (BFMeT)-treated rats were examined. Antioxidative
activity of the inhibitors was measured by a redox-linked colorimetric
method. RESULTS: Fluvastatin, which was reported to have antioxidative
activity, repressed the ileal ulcer formation in rats treated with BFMeT
an NSAIDs. However, the other HMG-CoA reductase inhibitors (pravastatin
and atorvastatin) did not repress the ileal ulcer formation. Among these
HMG-CoA reductase inhibitors, fluvastatin showed a significantly stronger
reducing power than the others (pravastatin, atorvastatin). CONCLUSION:
Fluvastatin having the antioxidaitive activity suppresses ulcer formation
in rats induced by NSAIDs.
Am J Cardiol. 2004 Jun 1;93(11):1419-21, A10.
Effect of fluvastatin therapy on coronary flow reserve in patients
with hypercholesterolemia.
Fujimoto K, Hozumi T, Watanabe H, Shimada K, Takeuchi M, Sakanoue Y, Shimizu
N, Ostuka R, Kawase Y, Sakamoto K, Yoshiyama M, Baba Y, Haze K, Yoshikawa
J.
Department of Internal Medicine and Cardiology, Osaka City University
Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Coronary flow reserve was evaluated using transthoracic Doppler echocardiography
before and after 3 months of fluvastatin therapy in patients with hypercholesterolemia.
Coronary flow reserve increased significantly after lipid-lowering therapy,
and coronary microcirculation was improved in patients with hypercholesterolemia.
Metabolism. 2004 Jun;53(6):733-9.
Fluvastatin improves endothelial dysfunction in overweight postmenopausal
women through small dense low-density lipoprotein reduction.
Shimabukuro M, Higa N, Asahi T, Oshiro Y, Takasu N.
Second Department of Internal Medicine, Faculty of Medicine, University
of the Ryukyus, Okinawa, Japan.
Small dense low-density lipoprotein (sdLDL), which are often associated
with obesity, are considered as the most atherogenic and have been shown
to impair endothelial function. It is not known whether reduction of sdLDL
by pharmacological intervention can improve endothelial function. Thirty-four
consecutive postmenopausal women with >/=5.70 mmol/L total cholesterol
were placed into either an overweight (body mass index [BMI] >/= 25.0,
n = 22) or a normal-weight (BMI < 25.0, n = 12) group, and forearm
blood flow (FBF) was measured using strain-gauge plethysmography during
reactive hyperemia before and after fluvastatin treatment. At baseline,
the peak FBF during reactive hyperemia in the overweight group was less
than that in the normal-weight group (mean +/- SD, 13.6 +/- 4.4 v 22.2
+/- 4.0 mL/min/100 mL, P <.01). The maximal FBF after nitroglycerin
was similar in both groups. In the stepwise multiple regression analysis,
only the concentration of sdLDL was the predictor for peak FBF (standard
coefficient = -0.517, P =.0115). The nonsignificant parameters for the
correlations in the model were age, BMI, systolic blood pressure, the
homeostasis model assessment of insulin resistance (HOMA-IR), hemoglobin
A(1c) (HbA(1c)), and LDL-cholesterol. Fluvastatin treatment was associated
with the recovery of the peak FBF in the overweight group but it did not
influence that of the normal-weight group. Changes in sdLDL fractions
by fluvastatin correlated well with the peak FBF recovery. These results
suggested that an increased sdLDL was linked to endothelial dysfunction
in overweight postmenopausal women and fluvastatin treatment improved
endothelial dysfunction by decreasing the atherogenic sdLDL fraction in
this population.
Cleve Clin J Med. 2003 Jun;70(6):561-6.
The Lescol Intervention Prevention Study (LIPS): start all patients
on statins early after PCI.
Messerli AW, Aronow HD, Sprecher DL.
Department of Cardiovascular Medicine, The Cleveland Clinic Foundation,
OH 44195, USA.
The Lescol Intervention Prevention Study (LIPS) was the first randomized
trial to show a significant reduction in the risk of cardiac events in
patients started on fluvastatin immediately after a successful percutaneous
coronary intervention. The benefit was independent of baseline cholesterol
levels. The results suggest that all patients should be discharged on
lipid-lowering therapy after a percutaneous coronary intervention. Currently,
this is seldom done.
Clin Ther. 2003 Mar;25(3):904-18.
Comparison of treatment with fluvastatin extended-release 80-mg
tablets and immediate-release 40-mg capsules in patients with primary
hypercholesterolemia.
Isaacsohn JL, LaSalle J, Chao G, Gonasun L.
Metabolic and Atherosclerosis Research Center, Cincinnati, Ohio, USA.
BACKGROUND: According to the National Cholesterol Education Program (NCEP)
Adult Treatment Panel (ATP) III guidelines, hypercholesterolemic patients
with greater risk for cardiovascular heart disease require more aggressive
lowering of low-density lipoprotein cholesterol (LDL-C) levels. Numerous
studies have demonstrated that despite these guidelines, patients often
do not reach their target levels, and that physicians frequently do not
titrate the drug beyond the starting dose. For these patients, it may
be more suitable to initiate treatment with a higher starting dose of
statin. With the immediate-release (IR) formulation of fluvastatin, the
maximal dose of 80 mg is recommended to be administered in divided doses
(40 mg BID). An extended-release (ER) formulation of fluvastatin at a
higher dose (fluvastatin ER 80 mg) was designed to provide greater LDL-C
lowering with QD dosing. Use of this formulation should bring more patients
into compliance with target LDL-C levels. OBJECTIVE: This analysis compared
the efficacy and tolerability of fluvastatin ER 80 mg QD and fluvastatin
IR 40 mg QD in lowering total cholesterol, LDL-C, triglyceride, and apolipoprotein
(apo) B levels and raising high-density lipoprotein cholesterol (HDL-C)
and apo A-I levels in patients with hypercholesterolemia over a 12-week
treatment period. METHODS: This was a prospective, multicenter, double-blind,
double-dummy, randomized, parallel-group, active-controlled study Patients
with primary hypercholesterolemia who qualified for lipid-lowering drug
therapy based on NCEP ATP II guidelines were randomized to fluvastatin
ER 80 mg QD or fluvastatin IR 40 mg QD, and treated for 12 weeks. RESULTS:
A total of 173 patients were randomized to treatment: 86 to the fluvastatin
ER 80-mg group and 87 to the fluvastatin IR 40-mg group. Compared with
fluvastatin IR 40 mg, fluvastatin ER 80 mg produced greater mean reductions
in LDL-C (32% vs 22%, respectively; P < 0.001). For each of the 3 coronary
heart disease (CHD) risk groups (defined by the NCEP), as well as for
the total population studied, more patients from the fluvastatin ER 80-mg
group than the IR 40 group achieved NCEP ATP II target LDL-C levels (79%
vs 47%, respectively [P = NS], for patients with < 2 risk factors;
58% vs 15%, respectively [P < 0.001], for patients with > or = 2
risk factors; and 40% vs 14%, respectively [P = 0.012], for patients with
CHD). The 80-mg ER dose of fluvastatin provided 9.1% greater LDL-C lowering
than the 40-mg IR dose. The incidence of elevations in transaminase levels
was low and similar for both doses, with 1 patient in each of the treatment
groups being discontinued due to repeated elevation of transaminases >
3 x the upper limit of normal (ULN). Clinically relevant elevations in
creatine kinase (ie, > or = 10x ULN) were not observed with either
dose. Nine patients (5 in the fluvastatin ER group and 4 in the fluvastatin
IR group) discontinued because of adverse events. CONCLUSIONS: Treatment
with fluvastatin ER 80 mg resulted in greater reductions in LDL-C, total
cholesterol, and apo B levels compared with fluvastatin IR 40 mg, with
clinically equivalent reduction in triglyceride levels and elevation of
HDL-C levels. Furthermore, there were few tolerability concerns of clinical
relevance with either formulation and no clinically meaningful difference
in the tolerability parameters between the 2 formulations. For patients
with higher baseline LDL-C levels, and for patients who require greater
LDL-C lowering, it may be appropriate to initiate therapy with fluvastatin
ER 80 mg. Use of the higher starting dose likely would bring a greater
proportion of high-risk patients into compliance with NCEP ATP II target
LDL-C levels and would provide LDL-C lowering that is in the same range
that has been proved in clinical trials to be associated with reductions
in CHD event rates.
Di Yi Jun Yi Da Xue Xue Bao. 2002 Dec;22(12):1109-11.
Effects of fluvastatin on the levels of C-reactive protein and
lipids in patients with hyperlipidemia.
Chi DS, Jin FX, Yang SG, Su YW, Ge B, Zhang J, Zhang Y, Liu YL.
Department of Cardiology, Nanfang Hospital, First Military Medical University,
Guangzhou 510515, China.
OBJECTIVE: To observe the changes of C-reactive protein (CRP) level and
its relationship with blood lipids, and the effects of fluvastatin on
CRP and the lipids in patients with hyperlipidemia. METHODS: Serum levels
of cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol
(HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density
lipoprotein cholesterol (VLDL-C) and lipoprotein(a)[Lp(a)] were measured
by enzyme assay, and plasma CRP level by immunonephelometry before and
after fluvastatin treatment (20 mg/d for 4 weeks) in patients with hyperlipidemia.
RESULTS: CRP levels were above normal in 90.3% hyperlipidemia cases in
spite of the various accompanying diseases. Fluvastatin treatment significantly
reduced TC (-7.49%), TG (-14.32%), LDL (-13.88%), VLDL (-18.48%) and TC/HDL(-13.50%)
levels (P<0.01), and also brought down Lp(a) concentration (-13.81%).
CRP levels was very effectively reduced after the treatment (-15.92%,
P<0.001). No association between basal CRP levels and basal lipids
and Lp(a) concentrations was observed. Positive correlation of CRP, however,
was observed after fluvastatin treatment with TC/HDL (r=0.62, P=0.041)
and Lp(a) (r=0.320, P=0.011), while inverse relations were noted between
CRP and HDL (r=-0.288, P=0.023). CONCLUSION: CRP levels increases markedly
in patients with hyperlipidemia, a fact that is independent of the accompanying
diseases. In addition to modulating blood lipid levels, fluvastatin also
reduces CRP level, the latter possibly serving as an independent predictive
factor for atherosclerotic cardiovascular diseases and also as an indicator
for estimating the effectiveness of the treatment.
J Clin Endocrinol Metab. 2002 Dec;87(12):5485-90.
Effect of fluvastatin slow-release on low density lipoprotein
(LDL) subfractions in patients with type 2 diabetes mellitus: baseline
LDL profile determines specific mode of action.
Winkler K, Abletshauser C, Hoffmann MM, Friedrich I, Baumstark MW, Wieland
H, Marz W.
Division of Clinical Chemistry, Department of Medicine, Albert Ludwigs-University,
D-79106 Freiburg, Germany.
The objective of this study was to determine the effect of slow-release
(XL) fluvastatin on low density lipoprotein (LDL) subfractions in type
2 diabetes. A multicenter, double-blind, randomized, parallel-group comparison
of fluvastatin XL 80 mg (n = 42) and placebo (n = 47), each given once-daily
for 8 wk, in 89 patients with type 2 diabetes (HbA1c: 7.2 +/- 1.0%, LDL
cholesterol (LDL-C): 3.4 +/- 0.7 mmol/liter, high density lipoprotein
cholesterol: 1.1 +/- 0.3 mmol/liter, and triglycerides (TG): 2.4 +/- 1.4
mmol/liter). At baseline and on treatment, plasma lipoproteins were isolated
and quantified. Eight weeks of fluvastatin treatment decreased total cholesterol
(-23.0%, P < 0.001), LDL-C (-29%, P < 0.001) and TG (-18%, P <
0.001), compared with placebo. At baseline, there was a preponderance
of dense LDL (dLDL) (apolipoprotein B in LDL-5 plus LDL-6 > 25 mg/dl)
in 79% of patients, among whom fluvastatin decreased all LDL subfractions,
reductions in dLDL being greatest (-28%, P = 0.001; cholesterol in dLDL
-29%). In patients with low baseline dLDL (apolipoprotein B in LDL-5 plus
LDL-6
Expert Opin Pharmacother. 2002 Nov;3(11):1631-41.
Fluvastatin.
Lawrence JM, Reckless JP.
Clinical Research Fellow, Diabetes and Lipid Research, Wolfson Centre,
Royal United Hospital, Bath, UK.
Fluvastatin was the first wholly synthetic statin to the market and is
effective in reducing total and low density lipoprotein cholesterol, which
translates into reductions in coronary heart disease events. The Lescol
Intervention Prevention Study has established the effectiveness of the
early use of statins in reducing recurrent events in high-risk patients
with coronary heart disease post percutaneous coronary interventions.
Fluvastatin is well-tolerated with few side effects. The occurrence of
significant abnormalities in liver enzymes is infrequent, and the risk
of myositis and rhabdomyolysis seems to be less than with other statins.
There have been no reports of fatal rhabdomyolysis to date. The potential
for drug interactions with fluvastatin is low. It seems safe in combination
with cyclosporin and there have been few reports of rhabdomyolysis when
using fluvastatin in combination with other lipid-lowering agents. It
is nevertheless important to be vigilant for this potentially important
side effect and, as with other statins, inform patients of the potential
risk and suggestive symptoms. Fluvastatin provides a useful option in
treating hypercholesterolaemia in patients at high risk of coronary heart
disease.
