Luokat: Kaikki - lipids - therapy - cholesterol - cardiovascular

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The Use of Statins in Reducing Cardiovascular Risk

Managing cardiovascular risk often involves addressing lipid levels in the body through various treatments. Pharmacological therapy includes the use of cholesterol absorption inhibitors like Ezetemibe, which lower LDL and total cholesterol by preventing their absorption in the GI tract.

The Use of Statins in Reducing Cardiovascular Risk

Lipids and Cardiovascular Risk

Treatment

Pharmacological Therapy
Sitostanol
Antioxidants
Fish Oils
Nicotinic Acid (niacin)
Bile acid-binding resins

E.g. colestyramine

Cholesterol Absorption Inhibitors (Ezetemibe)

Inhibits absorption of exogenous biliary cholesterol in the GI tract, reducing total cholesterol and LDL. Often used as an additive to statin instead of increasing the statin dose when side effects aren't tolerated.

Fibrates

Use reduces cardiovascular events but not overall mortality, therefore not routinely recommended in primary or secondary care

Mechanism of Action: Activate peroxisome proliferator-activated receptor alpha, leading to alterations in lipoprotein metabolism, therefore stimulating peripheral lipoprotein lipases which breakdown very low density lipoproteins (VLDLs) and some LDLs, whilst increasing levels of HDLs. It also leads to a reduction in triglycerides. However, increased biliary excretion of cholesterol can lead to gallstones

Gemofibrozil

Fenofibrate

Ciprofibrate

Bezafibrate

Statins (HMG-CoA Reductase Inhibitors)

Examples

Simvastatin

Rosuvastatin

Pravastatin

Fluvastatin

Atorvastatin

Mechanism of Action

Extensive first pass metabolism

Inhibit hepatic hydroxymethylglutaryl coenzyme A reductase (HMG-CoA reductase) which would otherwise catalyse the first step of cholesterol synthesis in the liver

Lifestyle and Diet Modification
Goals
Regression of atherosclerotic lesions
Reduce risk of MI and Stroke

Clinical Features

Coronary artery disease, presenting as angina or myocardial infarction
Xanthomas

Lab test date indicative of hyperlipidaemia

Total cholesterol > 5mmol/L
LDL:HDL > 3

Contributing Factors Towards the Development of Hyperlipidaemia

Modifiable Risk Factors
Infection associated with chronic inflammatory response
Reduced physical activity
Hyperglycaemia
Excess alcohol consumption
High-fat diet
Obesity
Smoking
Secondary to disease
Poorly Controlled Diabetes Mellitus
Renal Disease
Liver disease
Genetics
Drug-Induced
Oral Contraceptives containing levenorgestrel
Retinoids
Anabolic Steroids
Thiazide Diuretics
Corticosteroids
Beta blockers

Interactions

Co-morbidities
Peptic ulcer

Caution: Nicotinic Acid

Postmenopausal Osteoporosis

Statins may reduce bone turnover

Pregnancy

Contraception required whilst using and 3 months after

Statins, nicotinic acid and fibrates are contra-indicated in pregnancy and breastfeeding

Hypothyroidism

The condition itself may have adverse effects on a person's lipid profile

Increased risk of rhabdomyolysis with statins and fibrates

Gout

Use nicotinic acid in caution

Diabetes mellitus

Fibrates can improve glucose tolerance in combination with other hypoglycaemic agents. A reduction in the dose of hypoglycaemic agent may be necessary, particularly with clofibrate. Nicotinic acid should be used with caution

Renal impairment

May require dose reductions due to increased risk of rhabdomyolysis. Avoid MR benzofibrate.

Recent Heart Attack

Patients taking a statin before an MI are at an increased risk of further cardiac events for the following week if the statin is abruptly withdrawn at the time of the initial event.

Hypertension

Statins may lower blood pressure when used with antihypertensives

Thiazides raise cholesterole and triglycerides. Uncertainty over whether this is sustained

Gallstones

Can be caused by fibrates. Avoid in those who have gallbladder disease

Liver Disease

If severe avoid fibrates

Avoid statins

Medicine Interactions
Warfarin + Fish oil

Increased anticoagulation, additional monitoring

Macrolides e.g. erythromycin + simvastatin

Increased level of simvastatin, increased risk of rhabdomyolysis

Colesytramine + fluvastatin/pravastatin

Increased lipid lowering effect but reduced bioavailability of statin through colesytramine binding to it. Give several hours apart.

Grapefruit Juice + Simvastatin

High consumption can increase plasma concentration, advise patient to avoid. Smaller effect with atorvastatin, pravastatin appears unaffected

Orlistat + pravastatin

Possible increased levels of pravastatin

Ciclosporin + Fibrates/Statin

Increased levels of ciclosporin + increased risk of rhabdomyolysis (particularly with simvastatin/fibrates). Simvastatin is contra-indicated with ciclosporin and/or gemfibrozil. Pravastatin doesn't seem to interact.

Warfarin + fibrate/statin

Increased anti-coagulant effect with fibrate/SOME statins. Monitor INR

Simvastatin + CCBs e.g. amlodipine

Generally limit dose of simvastatin to 20mg in patients on amlodipine, verapamil or diltiazem. See: http://mm.wirral.nhs.uk/document_uploads/alerts/NWMICsummarysimvaamlodipineinteractionSep12.pdf

Fibrates + statins

Additional lipid lowering but increased risk of myopathy (rare). Caution.