Lipids and Cardiovascular Risk

Interactions

Medicine Interactions

Fibrates + statins

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

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

Warfarin + fibrate/statin

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

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.

Orlistat + pravastatin

Possible increased levels of pravastatin

Grapefruit Juice + Simvastatin

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

Colesytramine + fluvastatin/pravastatin

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

Macrolides e.g. erythromycin + simvastatin

Increased level of simvastatin, increased risk of rhabdomyolysis

Warfarin + Fish oil

Increased anticoagulation, additional monitoring

Co-morbidities

Liver Disease

Avoid statins

If severe avoid fibrates

Gallstones

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

Hypertension

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

Statins may lower blood pressure when used with antihypertensives

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before an MI are at an increased risk of further cardiac events for the following week if the statin is abruptly withdrawn at the time of the initial event.

Renal impairment

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

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

Gout

Use nicotinic acid in caution

Hypothyroidism

Increased risk of rhabdomyolysis with statins and fibrates

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

Pregnancy

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

Contraception required whilst using and 3 months after

Postmenopausal Osteoporosis

Statins may reduce bone turnover

Peptic ulcer

Caution: Nicotinic Acid

Contributing Factors Towards the Development of Hyperlipidaemia

Drug-Induced

Beta blockers

Corticosteroids

Thiazide Diuretics

Anabolic Steroids

Retinoids

Oral Contraceptives containing levenorgestrel

Genetics

Secondary to disease

Liver disease

Renal Disease

Hypothyroidism

Poorly Controlled Diabetes Mellitus

Modifiable Risk Factors

Hypertension

Smoking

Obesity

High-fat diet

Excess alcohol consumption

Hyperglycaemia

Reduced physical activity

Infection associated with chronic inflammatory response

Lab test date indicative of hyperlipidaemia

LDL:HDL > 3

Total cholesterol > 5mmol/L

Clinical Features

Xanthomas

Coronary artery disease, presenting as angina or myocardial infarction

Treatment

Goals

Reduce risk of MI and Stroke

Regression of atherosclerotic lesions

Lifestyle and Diet Modification

Pharmacological Therapy

Statins (HMG-CoA Reductase Inhibitors)

Mechanism of Action

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

Extensive first pass metabolism

Examples

Atorvastatin

Fluvastatin

Pravastatin

Rosuvastatin

Simvastatin

Fibrates

Examples

Bezafibrate

Ciprofibrate

Fenofibrate

Gemofibrozil

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

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

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.

Bile acid-binding resins

E.g. colestyramine

Nicotinic Acid (niacin)

Fish Oils

Antioxidants

Sitostanol