Statins are a class of drugs that lower cholesterol by inhibiting the enzyme HMG-CoA reductase. They work by competing with HMG-CoA for binding to the active site of the enzyme, which reduces cholesterol production in the liver. Common statins include atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin. Statins are prescribed to reduce cardiovascular disease risk, both as a primary prevention for those at high risk due to factors like age, cholesterol levels, blood pressure, or smoking, and as a secondary prevention for those who have already developed cardiovascular disease.

1. Dr. Kumbhare Manoj R.
Professor
S.M.B.T. College of Pharmacy
Dhamangaon Nashik (M.S.).
HMG-CoA reductase inhibitors

2. After successful completion of topic, a learner should
be able to-
Understand HMG-CoA reductase inhibitors or
statins
Know examples of statins
Explain applications of statins
Learning Outcome

3. Introduction
Mechanism of statins
Examples of statins
Applications of statins
Content

4. HMG-CoA reductase inhibitors also known
as Statins, are a class of lipid-lowering drugs that
reduce illness and mortality in those who are at high
risk of cardiovascular disease. They are the most
common cholesterol-lowering drugs.
Reduce risk for illnesses related to atherosclerosis,
with a varying degree of effect depending on
underlying risk factors and history of cardiovascular
disease. Clinical practice guidelines generally
recommend people start with lifestyle modification
through a cholesterol-lowering diet and physical
exercise.
Introduction

5. Low-density lipoprotein (LDL) carriers
of cholesterol play a key role in the development
of atherosclerosis and coronary heart disease via the
mechanisms described by the lipid hypothesis. Statins
are effective in lowering LDL cholesterol and so are
widely used for primary prevention in people at high
risk of cardiovascular disease, as well as in secondary
prevention for those who have developed
cardiovascular disease

6. Mechanism
The HMG-CoA reductase pathway, which is blocked by
statins via inhibiting the rate limiting enzyme HMG-CoA
reductase.
Statins act by competitively inhibiting HMG-CoA reductase,
the rate-limiting enzyme of the mevalonate pathway.
Because statins are similar in structure to HMG-CoA on a
molecular level, they will fit into the enzyme's active site and
compete with the native substrate (HMG-CoA). This
competition reduces the rate by which HMG-CoA
reductase is able to produce mevalonate, the next molecule
in the cascade that eventually produces cholesterol.

7. Inhibiting cholesterol synthesis
By inhibiting HMG-CoA reductase, statins block the
pathway for synthesizing cholesterol in the liver. This is
significant because most circulating cholesterol comes
from internal manufacture rather than the diet. When the
liver can no longer produce cholesterol, levels of
cholesterol in the blood will fall. Cholesterol synthesis
appears to occur mostly at night so statins with short half-
lives are usually taken at night to maximize their effect.
Studies have shown greater LDL and total cholesterol
reductions in the short-acting simvastatin taken at night
rather than the morning, but have shown difference in the
long-acting atorvastatin.

8. Statin Structre
Atorvastatin
Cerivastatin

9. Fluvastatin

10. Lovastatin
Mevastatin
Pitavastatin
Pravastatin
Rosuvastatin
Simvastatin

11. Applications
 For the primary prevention of cardiovascular disease,
the United States Preventive Services Task Force (USPSTF)
2016 guidelines recommend statins for those who have at
least one risk factor for coronary heart disease, are between
40 and 75 years old, and have at least a 10% 10-year risk of
heart disease. Risk factors for coronary heart disease
included abnormal lipid levels in the blood, diabetes
mellitus, high blood pressure, and smoking. They
recommended selective use of low-to-moderate doses
statins in the same adults who have a calculated 10-year
cardiovascular disease event risk of 7.5–10% or greater.In
people over the age of 70, statins decrease the risk of
cardiovascular disease but only in those with a history of
heavy cholesterol blockage in their arteries

12. Summary
Introduction
Mechanism of statins
Examples of statins
Applications of statins