To compare the rapidity of onset and the extent of oxidative stress lowering of atorvastatin with that of an (in terms of LDL lowering) equipotent dosage of simvastatin.
ID
Source
Brief title
Condition
- Coronary artery disorders
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Considering that there is no gold standard to measure effect on oxidative
stress, established parameters of oxidative stress such as oxidized LDL,
malondealdehyde and isoprostane will be measured in plasma and urine. All
parameters of oxidative stress before and during treatment with one of both
statins will be compared to determine whether atorvastatin causes a stronger
and quicker reduction of oxidative stress than simvastatin.
Secondary outcome
Niet van toepassing
Background summary
HMG-CoA reductase inhibitors (statins) are effective lipid-lowering agents and
are known to reduce cardiovascular events. Beneficial effects of statins seem
to occur very early in the course of their therapy and subgroup analysis of
large trials indicates that subjects in statin-treated arms have less
cardiovascular events than subjects in placebo-controlled arm with comparable
serum cholesterol levels. Therefore, it has been suggested that statins may
have antiatherogenic effects beyond their cholesterol lowering effect. Many
studies have demonstrated a rapid improvement in vascular function with
atorvastatine which cannot solely be accounted for by achieved lipid reduction.
A rapid oxidative stress lowering effect of atorvastatin has been proposed as
the probable mechanism of this action. Whether atorvastatine has stronger
antioxidant effect and whether atorvastatin lowers oxidative stress earlier in
the course of therapy than other statins has not been studied yet.
Study objective
To compare the rapidity of onset and the extent of oxidative stress lowering of
atorvastatin with that of an (in terms of LDL lowering) equipotent dosage of
simvastatin.
Study design
A randomised, double blind, parallel-group study design.
Intervention
All included patients are randomized to treatment with simvastatin 40 mg daily
or atorvastatin 10 mg daily to achieve a comparable lipid reduction.
Study burden and risks
After inclusion, all patients visit our oupatient clinic four times. Before
each visit a 24 hours urine sample is collected and during each visit blood
will be drawn.
Myopathy is a potential harmful side effect. In 1-7% of statin users muscle
complaints can appear due to myotoxicity and following myopathy. When myopathy
is not recognised in time, rhabdomyolysis may develop. In case of
rhabdomyolysis muscle damage can be so severe that in exeptional cases damage
to kidneys and other organs may develop with acute renal failure that could be
fatal.
During the visits a sample of blood will be drawn (total of 150 ml). This can
be inconvenient or painful and could result in haemorrage, swelling or local
inflammation.
De Boelelaan 1117
1081 HV Amsterdam
Nederland
De Boelelaan 1117
1081 HV Amsterdam
Nederland
Listed location countries
Age
Inclusion criteria
Patients in the age between 18 and 70 years, with diabetes mellitus type 2 and/or hypertension (RR > 140/90 mmHg) and/or obesity (BMI >25) and LDL > 2,5 mmol/l.
Exclusion criteria
Stage 5 chronic kidney disease
Use of an ACE inhibitor
Statin use in three months prior to inclusion
LDL cholesterol < 2,5 mmol/L
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | 00404599 |
| EudraCT | EUCTR2007-000608-34-NL |
| CCMO | NL15330.029.06 |