J Immunol. 2005 Feb 15;174(4):2327-35.
Suppression of autoimmune retinal disease by lovastatin does not
require th2 cytokine induction.
Gegg ME, Harry R, Hankey D, Zambarakji H, Pryce G, Baker D, Adamson
P, Calder V, Greenwood J.
Division of Cellular Therapy, and.
Intraocular inflammatory diseases are a common cause of severe
visual impairment and blindness. In an acute mouse model of autoimmune
retinal disease, we demonstrate that treatment with the 3-hydroxy-3-methylglutaryl
coenzyme A reductase inhibitor, lovastatin, suppresses clinical
ocular pathology, retinal vascular leakage, and leukocytic infiltration
into the retina. Efficacy was reversed by coadministration of
mevalonolactone, the downstream product of 3-hydroxy-3-methylglutaryl
coenzyme A reductase, but not by squalene, which is distal to
isoprenoid pyrophosphate metabolites within the cholesterol biosynthetic
pathway. Lovastatin treatment (20 mg/kg/day i.p.) over 7 days,
which resulted in plasma lovastatin hydroxyacid concentrations
of 0.098 +/- 0.03 muM, did not induce splenocyte Th2 cytokine
production but did cause a small reduction in Ag-induced T cell
proliferation and a decrease in the production of IFN-gamma and
IL-10. Thus, it is possible to dissociate the therapeutic effect
of statins in experimental autoimmune uveitic mice from their
activity on the Th1/Th2 balance. Statins inhibit isoprenoid pyrophosphate
synthesis, precursors required for the prenylation and posttranslational
activation of Rho GTPase, a key molecule in the endothelial ICAM-1-mediated
pathway that facilitates lymphocyte migration. Consistent with
inhibition of leukocyte infiltration in vivo, lovastatin treatment
of retinal endothelial cell monolayers in vitro leads to inhibition
of lymphocyte transmigration, which may, in part, account for
drug efficacy. Unlike lovastatin, atorvastatin treatment showed
little efficacy in retinal inflammatory disease despite showing
significant clinical benefit in experimental autoimmune encephalomyelitis.
These data highlight the potential differential activity of statins
in different inflammatory conditions and their possible therapeutic
use for the treatment of human posterior uveitis.
Am J Cardiol. 2004 Jun 15;93(12):1487-94.
Efficacy and safety of ezetimibe co-administered with simvastatin
compared with atorvastatin in adults with hypercholesterolemia.
Ballantyne CM, Blazing MA, King TR, Brady WE, Palmisano J.
Baylor College of Medicine, Houston, Texas, USA.
This study compared the efficacy and safety of co-administered
ezetimibe + simvastatin with atorvastatin monotherapy in adults
with hypercholesterolemia. Seven hundred eighty-eight patients
were randomized 1:1:1 to 3 treatment groups; each group was force-titrated
over four 6-week treatment periods: (1) 10 mg of atorvastatin
as the initial dose was titrated to 20, 40, and 80 mg; (2) co-administration
of 10 mg of ezetimibe and 10 mg of simvastatin (10/10 mg) was
titrated to 10/20, 10/40, and 10/80 mg of ezetimibe + simvastatin;
and (3) co-administration of 10/20 mg of ezetimibe + simvastatin
was titrated to 10/40 mg (for 2 treatment periods) and 10/80 mg
of ezetimibe + simvastatin. Key efficacy measures included percent
changes in low-density lipoprotein cholesterol (LDL) and high-density
lipoprotein cholesterol (HDL) from baseline to the ends of (1)
treatment periods 1 and 2 (for LDL cholesterol) comparing co-administration
of 10/20 mg and 10/10 mg of ezetimibe + simvastatin with 10 mg
of atorvastatin and (2) treatment period 4 (for LDL cholesterol
and HDL cholesterol) comparing co-administration of 10/80 mg of
ezetimibe + simvastatin with 80 mg of atorvastatin. Baseline LDL
and HDL cholesterol levels were comparable between treatment groups.
At the end of treatment period 1, the mean decrease of LDL cholesterol
was significantly.
Metabolism. 2004 Jun;53(6):744-8.
Simvastatin increases bone mineral density in hypercholesterolemic
postmenopausal women.
Lupattelli G, Scarponi AM, Vaudo G, Siepi D, Roscini AR, Gemelli
F, Pirro M, Latini RA, Sinzinger H, Marchesi S, Mannarino E.
Internal Medicine, Angiology and Atherosclerosis, Department of
Clinical and Experimental Medicine, University of, Perugia, Italy.
Statins are able to reduce cardiovascular morbility and mortality
mainly through their hypocholesterolemic effect. Beyond the inhibition
of cholesterol synthesis, the identification of "ancillary"
mechanisms has motivated studies evaluating the relationship between
the use of statins and the modification of bone mineral density
(BMD). To date, clinical trials have provided discordant results.
The aim of our study was to evaluate whether simvastatin treatment
(40 mg/d) could modify BMD in hypercholesterolemic women (n =
40) after a 2-year treatment as compared with a control group
treated only with diet (n = 20) and matched by gender, age, body
mass index (BMI), lipids, menopausal age, and BMD and the number
of osteopenic, osteoporotic, and normal women (on the basis of
T-score value). Exclusion criteria were secondary hyperlipemias
and osteoporosis and current or previous therapy with statins,
bisphosphonates, and estrogens. The BMD was measured at the lumbar
spine and hip by dual energy x-ray absorpiometry (DEXA). In the
group treated by simvastatin, BMD, both on the spine and femoral
hip, showed a significant increase after 8 and 24 months, respectively
(0.878 +/- 0.133 v 0.893 +/- 0.130 and 0.907 +/- 0.132; 0.840
+/- 0.101 v 0.854 +/- 0.101; and 0.863 +/- 0.10, P <.001);
there was a percentage increase of 1.7% after 8 months and 3.3%
after 24 months at the spine; at the femoral hip, BMD increased
1.6% after 8 months and 2.7% after 24 months. The group treated
only with hypolipidic diet demonstrated after 8 and 24 months
a slight decrease in BMD both on the spine and femoral hip (respectively,
0.884 +/- 0.175 v 0.872 +/- 0.174 and 0.861 +/- 0.164; 0.860 +/-
0.110 v 0.853 +/- 0.096 and 0.847 +/- 0.095; P <.05). In conclusion,
as partly suggested by retrospective or observational data, this
longitudinal study indicates that simvastatin treatment exerts
a beneficial effect on BMD.
Br J Community Nurs. 2004 Apr;9(4):160-5.
Statins and secondary prevention of coronary heart disease.
Ahmed M, Griffiths P.
A mini-review (Griffiths, 2002) of double-blind randomized controlled
trials (RCTs) was undertaken to assess the long-term effect of
lipid lowering treatments (statins versus placebo) in secondary
prevention of myocardial infarction (MI). The population sample
was adult patients with a history of MI, documented coronary heart
disease or coronary artery disease. The Cochrane Library and the
database Medline were searched and three RCTs appeared to possess
all of the stipulated inclusion and exclusion criteria. The trials
all compared statins against a placebo; one trial was of simvastatin--the
Scandinavian Simvastatin Survival Study (1994)--and the other
two were of pravastatin--the Cholesterol and Recurrent Events
Trial (CARE) (Sacks et al, 1996) and Long Term Intervention with
Pravastatin Ischaemic Disease (LIPID) (Anon, 1998). The trials
demonstrated that statins had a clear and consistent effect in
significantly reducing the risk of MI. Overall an approximate
decline of 30% in MI was produced from the three trials.
Lancet. 2004 May 15;363(9421):1607-8.
Oral simvastatin treatment in relapsing-remitting multiple sclerosis.
Vollmer T, Key L, Durkalski V, Tyor W, Corboy J, Markovic-Plese
S, Preiningerova J, Rizzo M, Singh I.
Barrow Neurological Institute, St Joseph's Hospital and Medical
Center, Phoenix, AZ, USA.
Many drugs have been approved for relapsing forms of multiple
sclerosis but are only partly effective, are injected, and are
expensive. We aimed to investigate use of of oral simvastatin
(80 mg) in 30 individuals with relapsing-remitting multiple sclerosis.
The mean number of gadolinium-enhancing lesions at months 4, 5,
and 6 of treatment was compared with the mean number of lesions
noted on pretreatment brain MRI scans. Number and volume of Gd-enhancing
lesions declined by 44%, (p<0.0001) and 41% (p=0.0018), respectively.
Treatment was well tolerated. Oral simvastatin might inhibit inflammatory
components of multiple sclerosis that lead to neurological disability.
Clin Oral Implants Res. 2004 Jun;15(3):346-50.
Simvastatin promotes osteogenesis around titanium implants.
Ayukawa Y, Okamura A, Koyano K.
Section of Oral Reconstructive Biotechnology, Division of Oral
Rehabilitation, Faculty of Dental Science, Kyushu University,
Japan.
OBJECTIVES: Hydroxymethylglutaryl-coenzyme A reductase inhibitors,
the so-called statins, have been widely used for hyperlipidemic
patients, and it was recently reported that it promoted bone formation.
In the present study, we examined the effect of simvastatin on
the promotion of osteogenesis around titanium implants. MATERIALS
AND METHODS: Ten 30-week-old rats received pure titanium implants
in both tibiae, and were then divided into experimental and control
groups. The experimental group was administered simvastatin daily.
Thirty days later, all animals were killed and then specimens
were prepared. The bone contact ratio (BCR) to the implant and
bone density (BD) around the implant, as well as histological
findings, were obtained. RESULTS: In the control group, newly
formed bone could be seen around the implants. It was seen to
be in direct contact with the implant surface, but otherwise unmineralized
connective tissue was occasionally interposed. In the medullary
canal, a scanty amount of bone trabeculae was observed. In the
experimental group, in contrast, thicker bone trabeculae were
abundantly seen in the medullary canal and showed a mesh-like
structure. In the histometrical observations, both BCR and BD
of the experimental group were significantly greater than those
of the control group. CONCLUSION: The administration of simvastatin
increases the value of both BCR and BD. This drug may have the
potential to improve the nature of osseointegration.
Mayo Clin Proc. 2004 May;79(5):620-9.
Efficacy and safety of ezetimibe coadministered with simvastatin
in patients with primary hypercholesterolemia: a randomized, double-blind,
placebo-controlled trial.
Goldberg AC, Sapre A, Liu J, Capece R, Mitchel YB; Ezetimibe Study
Group.
Lipid Research Clinic, Washington University, St Louis, MO 63110-1093,
USA.
OBJECTIVE: To compare the efficacy and safety of 10 mg of ezetimibe
coadministered with simvastatin with the safety and efficacy of
simvastatin monotherapy for patients with hypercholesterolemia.
PATIENTS AND METHODS: This multicenter double-blind, placebo-controlled,
factorial study enrolled 887 patients with hypercholesterolemia
(low-density lipoprotein cholesterol [LDL-C], 145-250 mg/dL; triglycerides,
< or = 350 mg/dL). Patients were randomized to 1 of 10 treatments--placebo,
ezetimibe at 10 mg/d, simvastatin at 10, 20, 40, or 80 mg/d, or
simvastatin at 10, 20, 40, or 80 mg/d plus ezetimibe at 10 mg/d
for 12 weeks. The study began March 13, 2001, and ended January
8, 2002. The primary efficacy end point was the mean percent change
in LDL-C levels from baseline to study end point (last available
postbaseline LDL-C measurement) for the pooled ezetimibe/simvastatin
group vs the pooled simvastatin monotherapy group. RESULTS: Coadministration
of ezetimibe/simvastatin was significantly (P<.001) more effective
than simvastatin alone in reducing LDL-C levels for the pooled
ezetimibe/simvastatin vs pooled simvastatin analysis and at each
specific dose comparison. The decrease in LDL-C levels with coadministration
of ezetimibe and the lowest dose of simvastatin, 10 mg, was similar
to the decrease with the maximum dose of simvastatin, 80 mg. A
significantly (P<.001) greater proportion of patients in the
ezetimibe/simvastatin group achieved target LDL-C levels compared
with those in the monotherapy group. Treatment with ezetimibe/simvastatin
also led to greater reductions in total cholesterol, triglyceride,
non-high-density lipoprotein cholesterol, and apolipoprotein B
levels compared with simvastatin alone; both treatments increased
high-density lipoprotein cholesterol levels similarly. The safety
and tolerability profiles for the ezetimibe/simvastatin and monotherapy
groups were similar. CONCLUSION: Through dual inhibition of cholesterol
absorption and synthesis, coadministration of ezetimibe/simvastatin
offers a highly efficacious and well-tolerated lipid-lowering
strategy for treating patients with primary hypercholesterolemia.
J Clin Endocrinol Metab. 2003 Jul;88(7):3021-6.
Lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase
inhibitor, induces apoptosis and differentiation in human anaplastic
thyroid carcinoma cells.
Wang CY, Zhong WB, Chang TC, Lai SM, Tsai YF.
Graduate Institute of Physiology, College of Medicine, National
Taiwan University, Taipei, Taiwan.
Although only 1% of differentiated thyroid cancers transform into
anaplastic thyroid cancer, this disease is always fatal. Differentiation
therapy may provide a new therapeutic approach to increasing the
survival rate in such patients. 3-Hydroxy-3-methylglutaryl coenzyme
A (HMG-CoA) reductase inhibitors are reported to promote cellular
apoptosis and differentiation in many cancer cells; these effects
are unrelated to lipid reduction. Recently, we found that TNFalpha
induces cytomorphological differentiation in anaplastic thyroid
cancer cells and increases thyroglobulin expression; however,
TNF is cytotoxic for normal human tissue. The aim of this study
was to determine whether lovastatin, an HMG-CoA reductase inhibitor,
could induce apoptosis and differentiation in anaplastic thyroid
cancer cells. Anaplastic thyroid cancer cells were treated with
lovastatin, then examined for cellular apoptosis and cytomorphological
differentiation by DNA fragmentation, phosphatidylserine externalization/flow
cytometry, and electron microscopy. Thyroglobulin levels in the
culture medium were also measured. Our results showed that at
a higher dose (50 micro M), lovastatin induced apoptosis of anaplastic
thyroid cancer cells, whereas at a lower dose (25 micro M), it
promoted 3-dimensional cytomorphological differentiation. It also
induced increased secretion of thyroglobulin by anaplastic cancer
cells. Our results show that lovastatin not only induces apoptosis,
but also promotes redifferentiation in anaplastic thyroid cancer
cells, and suggest that it and other HMG-CoA reductase inhibitors
merit further investigation as differentiation therapy for the
treatment of anaplastic thyroid cancer.
Nat Rev Drug Discov. 2003 Jul;2(7):517-26.
Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors.
Tobert JA.
Merck Research Laboratories, Rahway, New Jersey 07065, USA.
In the 1950s and 1960s, it became apparent that elevated concentrations
of plasma cholesterol were a major risk factor for the development
of coronary heart disease, which led to the search for drugs that
could reduce plasma cholesterol. One possibility was to reduce
cholesterol biosynthesis, and the rate-limiting enzyme in the
cholesterol biosynthetic pathway, 3-hydroxy-3-methyl-glutaryl-CoA
(HMG-CoA) reductase, was a natural target. Here, I describe the
discovery and development of lovastatin--the first approved inhibitor
of HMG-CoA reductase--and the clinical trials that have provided
the evidence for the ability of drugs in this class to reduce
the morbidity and mortality associated with cardiovascular disease.
Drugs. 2003;63(7):685-99.
Lovastatin extended release: a review of its use in the management
of hypercholesterolaemia.
Curran MP, Goa KL.
Adis International Limited, Auckland, New Zealand.
Lovastatin extended release (ER) provides a new form of delivery
for lovastatin, an HMG-CoA reductase inhibitor. Lovastatin ER
delivers the drug in a more sustained fashion, as shown by a smoother
plasma concentration-time profile, a lower maximum plasma concentration
and a prolonged half-life compared with that of lovastatin immediate
release (IR). At dosages of 10-60 mg/day, lovastatin ER significantly
reduced levels of total cholesterol, low density lipoprotein (LDL)-cholesterol
and triglycerides, and increased levels of high density lipoprotein-cholesterol,
in patients with primary hypercholesterolaemia in a randomised,
double-blind study of 12 weeks' duration. These effects were maintained
in a 6-month extension study in which patients received lovastatin
40 or 60 mg/day. In a randomised 4-week study in 24 patients with
primary hypercholesterolaemia, the reduction in plasma LDL-cholesterol
levels was significantly greater with lovastatin ER 40 mg/day
than with the IR formulation administered at the same dosage.
Lovastatin ER was well tolerated in all studies and adverse events
were usually mild to moderate and transient. The tolerability
profile of lovastatin ER was similar to that of lovastatin IR.
There were no reports of clinically relevant elevations in liver
transaminases or creatine phosphokinase attributed to the drug
in recipients of lovastatin ER. CONCLUSION: The ER formulation
of lovastatin provides smooth and sustained delivery of this established
and well-tolerated agent over the dosage interval, significantly
reducing LDL-cholesterol in patients with primary hypercholesterolaemia.
If, as expected, the beneficial changes in lipid levels are maintained
during long-term treatment and further clinical experience confirms
the greater efficacy of the lovastatin ER formulation than the
IR formulation, then lovastatin ER is likely to supplant lovastatin
IR and provide a useful option in the management of patients with
dyslipidaemia and prevention of coronary heart disease.
Leukemia. 2002 Jul;16(7):1362-71.
The cholesterol lowering drug lovastatin induces cell death in
myeloma plasma cells.
van de Donk NW, Kamphuis MM, Lokhorst HM, Bloem AC.
Department of Immunology, University Medical Center Utrecht, The
Netherlands.
Lovastatin is an irreversible inhibitor of HMG-CoA reductase and
blocks the production of mevalonate, a critical compound in the
production of cholesterol and isoprenoids. Isoprenylation of target
proteins, like the GTP-binding protein Ras, is essential for their
membrane localization and subsequent participation in intracellular
signaling cascades. Lovastatin effectively decreased the viability
of plasma cells from cell lines (n = 10) and myeloma patients'
samples (n = 8) in a dose- and time-dependent way. Importantly,
co-incubation of lovastatin with dexamethasone had a synergistic
effect in inducing plasma cell cytotoxity. This effect was not
the consequence of a change in the protein expression levels of
Bcl-2 or Bax induced by lovastatin. The decrease in plasma cell
viability was the result of induction of apoptosis and inhibition
of proliferation. Mevalonate effectively reversed the cytotoxic
and cytostatic effects of lovastatin in plasma cells. The cytotoxic
activity of lovastatin was higher in Pgp expressing cell lines,
but did not correlate with the multidrug resistance (MDR)-related
proteins LRP, Bcl-2 and Bax. Lovastatin treatment resulted in
a shift of Ras localization from the membrane to the cytosol that
was reversed by mevalonate. The data presented in this paper warrant
study of lovastatin alone or in combination with therapeutic drugs,
in the treatment of myeloma patients.
Am J Cardiol. 2002 Jun 15;89(12):1374-80.
The liver and lovastatin.
Tolman KG.
University of Utah School of Medicine, Salt Lake City, Utah 84132,
USA.
The cholesterol-lowering agents, known as statins, have been in
use for 15 years and are among the most commonly prescribed drugs.
Animal studies and premarketing clinical trials have given signals
of hepatotoxicity, primarily minor elevations in serum alanine
aminotransferase enzyme (ALT) levels. For that reason, all of
the cholesterol-lowering drugs have labeling that requires monitoring
of liver enzymes. Postmarketing experience, however, suggests
that hepatotoxicity is rare and thus it is timely to revisit the
issue. The first of the statins, lovastatin, was approved in 1986
and has acquired 24 million patient-years of clinical experience.
Minor elevations in liver enzymes, i.e., ALT 3 x the upper limit
of normal (ULN) occur in 2.6% and 5.0% of patients on lovastatin
doses of 20 and 80 mg/day, respectively. These elevations are
reversible with continuing therapy, are dose related, and are
probably related to cholesterol lowering per se. Rare cases of
acute liver failure (ALF) have been reported with all of the cholesterol-lowering
drugs. With lovastatin, the rate is approximately 1/1.14 million
patient-treatment years, which is 9% of the background rate of
all causes of ALF and approximately equal to the background rate
of idiopathic ALF. Monitoring for hepatotoxicity has not been
effective in preventing serious liver disease, largely because
of its rarity and the poor predictive value of minor ALT elevations.
In fact, it may increase patient risk because of needless discontinuation
of cholesterol-lowering therapy for false-positive results in
patients who are benefiting from treatment.
Leuk Lymphoma. 2000 Dec;40(1-2):167-78.
Lovastatin induces a pronounced differentiation response in acute
myeloid leukemias.
Dimitroulakos J, Thai S, Wasfy GH, Hedley DW, Minden MD, Penn
LZ.
Department of Cellular and Molecular Biology, Ontario Cancer Institute,
University Health Network, Toronto, Canada.
We recently identified HMG-CoA reductase, the rate-limiting enzyme
of the mevalonate pathway, as a potential therapeutic target of
various retinoic acid responsive cancers. Lovastatin, a competitive
inhibitor of HMG-CoA reductase, induced a retinoic acid-like differentiation
response followed by extensive apoptosis in neuroblastoma cell
lines at relatively low concentrations (<20 microM) of this
agent. More recently, we demonstrated that acute myeloid leukemias
but not acute lymphocytic leukemias also displayed increased sensitivity
to lovastatin-induced apoptosis. In this study, we examined the
ability of lovastatin to induce differentiation of acute myeloid
leukemic cells and to evaluate the role differentiation may hold
in the anti-leukemic properties of this agent. Increased expression
of the leukocyte integrins CD11b and CD18 as well as down-regulation
of the anti-apoptotic gene bcl-2 are associated with late stage
differentiation of the myeloid lineage and retinoic acid induced
maturation of acute myeloid leukemic cells. Lovastatin exposure
induced increased expression of CD11b and CD18 markers similar
to retinoic acid treatment. Following 24 hrs exposure to 20 microM
lovastatin, all 7 acute myeloid leukemia cell lines tested showed
a decrease in bcl-2 mRNA expression while only 1/5 acute lymphocytic
leukemia cell lines showed a similar response. A role for bcl-2
in the apoptotic response of acute myeloid leukemia cells to lovastatin
was demonstrated as exogenous constitutive expression of bcl-2
in the AML-5 cell line inhibited apoptosis in a time and dose
dependent manner. Thus, lovastatin exposure of acute myeloid leukemia
cells induced a differentiation response that may contribute to
the therapeutic potential of this agent in the treatment of this
disease.
Ter Arkh. 1996;68(12):72-5.
The characteristics of the hypolipidemic effect of Mevacor with
its permanent multiyear use.
Lipovetskii BM.
Changes in blood lipids were assessed in the course of 4 years
in 29 patients with cholesterol (CS) levels at least 300 mg/dl
(hyperlipidemia). Of these, 20 received mevacor, 9 were controls.
Taking mevacor in a dose 20-40 mg/day for 6 months reduced CS
in the study group by 20% and by 10% more within the next 6 months.
CS in controls changed unnoticeably. Lowering of the dose to 10-20
mg/day or mevacor discontinuation at the moment CS fell to 250
mg/dl or greater did not entail a rerise of total blood CS within
subsequent 4-6 months.
Bratisl Lek Listy. 1994 Oct;95(10):457-60.
Biochemical and functional study of the liver during treatment
of familial hyperlipoproteinemia with Mevacor (lovastatin) and
Vasosan S (cholestyramine)
Kolesar P, Raslova K, Ulicna O, Kupcova V, Mojto V.
III. interna klinika LFUK, Bratislave.
The aim of our study was the biochemical and functional examination
of the liver during the therapy of familiar hyperlipoproteinemia
by means of MevacorR (lovostatine) in comparison with the treatment
by Vasosan S (cholestyramine). We examined 20 patients treated
with a daily dose of MevacorR being 20-40 mg and, 18 patients
treated with a daily dose of Vasosan S being 16-32 g for the period
of 12 weeks. During the therapy the total cholesterol, LDL-cholesterol,
HDL-cholesterol, triacylglycerols, hepatic enzymes (AST, ALT,
ALP) activity, functional test of the liver, biological half-time
of antipyrine (t 1/2 antipyrine) were investigated at the onset
and at the end of the study. We discovered that at the end of
the treatments by MevacorR and Vasosan S the hypolipidemic effect
increased (cholesterol p < 0.001, LDL cholesterol p < 0.001),
and there was difference in the effect on HDL-cholesterol and
in that on triacylglycerols. During the treatment we discovered
that due to both medicaments the liver enzymes activity increased
to a different extent. At the beginning of the study the antipyrine
biological half-time statistically increased in both investigated
groups, namely in comparison with the control group. At the end
of the treatments in both groups the antipyrine half-time was
prolonged, however not significantly. Prior to long-term therapy
by hypolipidemics the authors recommend biochemical and functional
examination of the liver.
Probl Endokrinol (Mosk). 1992 Nov-Dec;38(6):34-5.
Use of the lipolytic drug mevacor in the treatment of patients
with diabetes mellitus.
Balabolkin MI, Mamaeva GG, Poliakova IA, Kniazeva AP.
Stable compensation of diabetes mellitus, including normolipidemia,
underlies the therapy of diabetic angiopathies. Mevacor represents
a nonactive lactone form of a certain hydroxy acid, a potent inhibitor
of endogenous synthesis of cholesterol, conducive to blood cholesterol
reduction. The aim of the present study was the assessment of
the efficacy of this drug in therapy of patients with diabetes
mellitus. Ten patients were administered mevacor in a dose of
20 mg for a month. Such therapy was conducive to a significant
reduction of the levels of cholesterol, LNP cholesterol, triglycerides,
and cholesterol/LVP ratio. It also promoted a reduction of the
content of lipid peroxidation products in the blood, these products
being an active factor of vessel destruction. The levels of hydroperoxides,
blood serum and red cell malonic dialdehyde, and superoxide dismutase
were also reduced. These results necessitate addition of mevacor
to a complex of therapy for diabetes to normalize lipid metabolism.
Kardiologiia. 1992 Jun;32(6):19-21.
Effects of lovastatin (mevacor) on platelet function in hypercholesterolemia
in patients with ischemic heart disease.
Shalaev SV, Safiullina ZM, Zhuravleva TD, Nikitina VI, Baranova
TA.
The impact of a 4-week course of lovastatin (mevacor) therapy
on platelet function was examined in 26 patients with coronary
heart disease concurrent with hypercholesterolemia (the baseline
plasma cholesterol level was 250 mg% or more). The agent was given
in a daily dose of 20-40 mg. The agent in this dose was found
to have no action on the thromboxane-prostacyclin balance in plasma,
on the degree of ADP-induced aggregation and lipid peroxidation
in platelets, phospholipid composition and levels of ester-bound
cholesterol in platelet membranes. Free cholesterol tended to
increase at the end of the 4th week of treatment. Despite the
effective reduction of plasma levels of total and LDL cholesterols
whose action on platelets is well known, there was no estimated
decrease in the activity of platelets during lovastatin therapy.
Ugeskr Laeger. 1990 Nov 5;152(45):3354-7.
Treatment of severe primary hypercholesterolemia with lovastatin
(Mevacor). A new therapeutic principle.
Leth A, Munch M, Nielsen B, Dollerup J.
Kobenhavns Amts Sygehus i Glostrup, lipidambulatoriet, medicinsk
afdeling C.
An open clinical trial comprising 59 outpatients with severe hypercholesterolemia
(including 35 patients with familial hypercholesterolaemia) and
considerable predisposition to ischaemic cardiac disease revealed
a dosage-related pronounced effect of lovastatin on serum cholesterol
and subfractions of this. After dietary regulation for a period
of four months, a decrease in serum cholesterol of 11.7% was observed
and after further treatment for six months with lovastatin with
an average dose of 59 mg per 24 hours, the serum cholesterol decreased
with a total of 45% of original value. Low density lipoprotein
(LDL)-cholesterol decreased 44% and high density lipoprotein (HDL)-cholesterol
increased by over 21%. Serum triglyceride fell by 20%. The serum-cholesterol/HDL-cholesterol
ratio was reduced from 8.8 to 4.9. Only slight and transient subjective
side-effects were observed and none of the patients dropped out
of the trial for this reason. One patient with recognized ischaemic
heart disease died from myocardial infarction. A tendency towards
increasing liver parameters and creatin kinase was observed in
the group as a whole but was not significant.
