Cardiovascular Disease Prevention with Lipid Drugs

Lipid Lowering Drugs for Cardiovascular Disease Prevention

• Lipid-lowering drugs are used to treat cardiovascular disease.
• People at risk of early death from cardiovascular disease should have lifestyle changes and lipid modification therapy.
• Identifying and assessing cardiovascular disease risk is a key aspect of prevention.

Primary Prevention of Statins in Cardiovascular Disease

• Offer atorvastatin 20 mg for primary prevention of cardiovascular disease to people with a 10% or greater 10-year risk of developing cardiovascular disease.
• For people aged 85 and older, consider atorvastatin 20 mg, as statins may reduce the risk of non-fatal myocardial infarction.
• Primary dyslipidemia is a combination of dietary and genetic factors. Familial hypercholesterolemia (FH) is a high risk for coronary heart disease (CHD).
• Secondary dyslipidemia is a consequence of other conditions like diabetes, alcoholism, and renal disease.

Treating Dyslipidemia Pharmacologically and Non-Pharmacologically

• Non-pharmacological methods include a cardioprotective diet, weight loss, physical activity, and reduced alcohol consumption and smoking cessation.
• Pharmacologically, anti-hyperlipidaemic drugs are used.

Different Lipid Lowering Drugs

• HMG-CoA reductase inhibitors
• Fibrates
• Cholesterol absorption inhibitors (Ezetimibe & Bile-acid binding resins)
• Omega fatty acids
• Nicotinic acid

HMG-CoA Reductase Inhibitors

• Simvastatin, Pravastatin, Lovastatin, Atorvastatin, Rosuvastatin, and Fluvastatin are examples.
• They block HMG-CoA reductase, a crucial enzyme in cholesterol synthesis.
• Short-acting and specific inhibitors include Simvastatin and Lovastatin.
• Long-lasting inhibitors include Atorvastatin.
• These drugs increase LDL receptor synthesis and increase LDL clearance.
• They are mostly short-acting and oral, typically taken at night.
• Liver metabolism, primarily by CYP450s, is a key aspect, with some exceptions.
• Clinical use includes preventing FH, reducing LDL (30%) and increasing HDL (20%), providing secondary prevention for MI and stroke.
• Potential adverse effects include muscle pain and gastrointestinal problems.

Beneficial Effects of HMG-CoA Reductase Inhibitors

• Improved endothelial function
• Improved vascularisation of ischaemic tissue
• Atherosclerotic plaque stabilisation
• Reduction in vascular inflammatory response
• Reduction in platelet activation
• Enhanced fibrinolysis
• Antithrombotic properties

Fibrates

• Gemfibrozil, Fenofibrate, Bezafibrate are examples.
• They act as agonists at peroxisome-activated receptor-alpha (PPAR-alpha).
• They increase lipoprotein lipase synthesis, increase fatty acid oxidation, and increase LDL uptake.
• They reduce VLDL and TG, with modest reduction in LDL.
• They can be helpful for hypertriglyceridemia and mixed hyperlipidemia.
• Metabolized by CYP450s and renal excretion is common.
• Potential adverse effects include rash, gastrointestinal problems, and rare cases of rhabdomyolysis (muscle breakdown) potentially leading to kidney damage.

Cholesterol Absorption Inhibitors

• Ezetimibe, is used to inhibit cholesterol absorption.
• It works by affecting Niemann-Pick C1-like 1 (NPC1L1) transport protein.
• It's absorbed into intestinal cells.
• Clinical use for hyperlipidemia often in combination with statins.
• Adverse effects include mild diarrhea and abdominal pain.

Colestipol and Cholestyramine, Cholesterol Absorption Inhibitors

• These bind to bile acids in the gut, preventing reabsorption.
• They increase LDL receptors, thus increasing LDL removal from the blood.
• They are administered orally.
• Clinical Use is for primary hypercholesterolemia.
• Associated potential adverse effects include constipation, bloating, malabsorption of certain vitamins and minerals.

Nicotinic Acid (Niacin)

• Reduces VLDL synthesis in the liver.
• Reduces hormone-sensitive lipase activity in adipose tissue.
• Increases HDL levels.
• Increases VLDL and TG clearance.
• It's readily absorbed, metabolized in the liver, and excreted via the kidneys.
• Clinical use is for hypercholesterolemia and hypertriglyceridemia, particularly with low HDL levels.
• Common adverse effects include flushing and pruritus (itchiness).