The role of statin drugs in combating cardiovascular diseases

Suresh Pichandi et al. / Int J Cur Sci Res. 2011; 1(2): 47 - 56.

Table.1.Brand Name, Derivation and Metabolism of Statin Drugs[1].

The indications for the prescription of statins have broadened
over the years. Initial studies, such as the Scandinavian
Simvastatin Survival Study (4S), supported the use of statins in
secondary prevention for cardiovascular disease, or as primary
prevention only when the risk for cardiovascular disease was
significantly raised, as indicated by the Framingham risk score.
Indications were broadened considerably by studies such as the
Heart Protection Study (HPS), which showed preventative effects
of statin use in specific risk groups, such as diabetics. The
ASTEROID trial, published in 2006, using only a statin at high dose,
achieved lower than usual target calculated LDL values and
showed disease regression within the coronary arteries using
intravascular ultrasonography[2].

Statins are generally accepted as effective in decreasing
mortality in people with preexisting cardiovascular disease. They
are also currently advocated for use in patients at high risk of
developing heart disease, but the evidence for this is questioned. A
2010 meta-analysis of studies found no benefit in terms of all-
cause mortality when statins were used as a high-risk primary
prevention intervention.

1.4.Comparative effectiveness

An independent analysis has been done to compare
atorvastatin, pravastatin and simvastatin, based on their
effectiveness against placebos. It found that, at commonly
prescribed doses, there are no statistically significant differences
amongst statins in reducing cardiovascular morbidity and
mortality. The CURVES study, which compared the efficacy of
different doses of atorvastatin, simvastatin, pravastatin, lovastatin,
and fluvastatin for reducing LDL and total cholesterol in patients
with hypercholesterolemia, found that atorvastatin was more
effective without increasing adverse events[Table.2].

Statins differ in their ability to reduce cholesterol levels. Doses
should be individualized according to patient characteristics such
as goal of therapy and response. After initiation and/or dose
changes, lipid levels should be analyzed within 1-3 months and
dosage adjusted accordingly, then every 6-12 months afterwards.
A link between cholesterol and cardiovascular disease, known as
the lipid hypothesis, had already been suggested [3,4].

1.5.Effects of Statin

Statins exhibit action beyond lipid-lowering activity in the
prevention of atherosclerosis. The ASTEROID trial showed direct
ultrasound evidence of atheroma regression during statin
therapy.Researchers hypothesize that statins prevent
cardiovascular disease via four proposed mechanisms (all subjects
of a large body of biomedical research):

1. Improve endothelial function

2. Modulate inflammatory responses

3. Maintain plaque stability

4. Prevent thrombus formation

Cholesterol is the main constituent of atheroma, the fatty lumps in
the wall of arteries that occur in atherosclerosis and, when
ruptured, cause the vast majority of heart attacks, Treatment
consisted mainly of dietary measures such as a low-fat diet, and
poorly tolerated medicines such as clofibrate, cholestyramine and
nicotinic acid.Cholesterol researcher Daniel Steinberg writes that
while the Coronary Primary Prevention Trial of 1984
demonstrated that cholesterol lowering could significantly reduce
the risk of heart attacks and angina, physicians, including
cardiologists, remained largely unconvinced[5].

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