STATIN

From introduction to application

Outline
• Introduction
• Drug Mechanism
• Statin in guideline
• Side Effect
Introduction
 Physiology
of Lipid Metabolism

Fundamentals of Anatomy and Physiology 11th edition, Martini

 Lipid-Lowering Therapies

Opie’s Cardiovascular Drugs: A Companion to Braunwald’s Heart Disease

Lipoprotein & Atherosclerosis

Ahmadi A, Argulian E, Leipsic J, Newby DE, Narula J. From Subclinical Atherosclerosis to Plaque Progression and Acute Opie’s Cardiovascular Drugs:
Coronary Events: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019 Sep 24;74(12):1608-1617. doi:
10.1016/j.jacc.2019.08.012. PMID: 31537271. A Companion to Braunwald’s Heart Disease
 Statin
(3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors)

• Statins are well established as the first drugs of choice in primary and secondary
prevention of CHD because of their favorable clinical outcomes, predictable effects on
LDL-C, and relatively few side effects across multiple large clinical trials.
• Available statins include
• Lovastatin,
• Pravastatin,
• Simvastatin,
• Fluvastatin,
• Atorvastatin,
• Rosuvastatin, And
• Pitavastatin.
• All the statins decrease hepatic cholesterol synthesis by inhibiting 3-hydroxy-3-
methylglutaryl coenzyme A (HMG-CoA) reductase.

Opie’s Cardiovascular Drugs: A Companion to Braunwald’s Heart Disease

Statin
Therapy
Mechanism of Action

Inhibition of cholesterol synthesis by statins (Source- Lippincott’s Illustration of Pharmacology)

Statin in Guideline
ESC 2019
Side Effect

Adhyaru, B.B., Jacobson, T.A. Safety and efficacy of statin therapy. Nat Rev Cardiol 15, 757–769 (2018).
https://doi.org/10.1038/s41569-018-0098-5
Side Effect
• New-onset diabetes is a more recently discovered side effect, first reported with rosuvastatin
and now recognized as a generalized problem of high-dose statins.
• In a meta-analysis of 91,140 persons in 13 trials, statin therapy was associated with a slightly
increased risk of new diabetes (9%, odds ratio 1.09; 95% CI 1.02–1.17). Based on these data,
statin therapy used in 255 patients for 4 years led to one extra case of diabetes and prevented 5.4
coronary events (coronary deaths, nonfatal MI).
• In another meta-analysis, which compared intensive- with moderate-dose statin therapy in five
studies that included 32,752 persons without diabetes at baseline, the NNT annually was 498 for
new-onset diabetes versus 155 for reduced cardiovascular events. Thus, the approximate ratio of
benefit to harm for high versus medium doses was approximately 3:1.
• An observational study of 161,808 postmenopausal women found an increase in risk for diabetes
(48%, multivariate-adjusted HR 1.48; 95% CI 1.38–1.59). As a result of this cumulative
evidence, the FDA has added information concerning an effect of statins on incident diabetes and
increases in hemoglobin A1c and fasting plasma glucose to all statin labels.

Opie’s Cardiovascular Drugs: A Companion to Braunwald’s Heart Disease

Side Effect
• Additional information about potential nonserious and reversible
cognitive side effects (memory loss, confusion, etc.) were also added
to statin labels, based on postmarketing reports. However in the
PROSPE trial, cognitive function was assessed repeatedly in all 5804
participants, and no difference was found in cognitive decline in
subjects treated with pravastatin compared with placebo during a 3-
year follow-up period. Similarly, a systematic review and meta-
analysis found no difference in cognitive performance related to
procedural memory, attention, or motor speed.

Opie’s Cardiovascular Drugs: A Companion to Braunwald’s Heart Disease