Non-prescription medicines for the prevention of cardiovascular disease

Non-prescription medicines for the prevention of cardiovascular disease 

Simvastatin

• Simvastatin is one of a group of drugs known as statins that act by competitively inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the enzyme that mediates cholesterol synthesis in the liver.
• Inhibition of HMG-CoA increases the formation of low-density lipoprotein (LDL) receptors on hepatocyte membranes, leading to increased clearance of LDL cholesterol and reduction in total serum cholesterol.
• The main biochemical effect of the statins is to lower LDL cholesterol, but they also raise levels of high-density lipoprotein (HDL) cholesterol, which improves the HDL:LDL cholesterol ratio (a more important index than total serum cholesterol), and they also reduce plasma triglycerides.
• Statins have been shown to be safe and effective in lowering cholesterol, and it has been recommended that a statin should be prescribed as secondary prevention for all patients with symptomatic cardiovascular disease.
• Statins have also been recommended for all people without symptoms but who are considered to be at moderate risk (i.e. 10–15% risk of developing coronary heart disease (CHD) within the next 10 years); it is possible to determine moderate risk through self-reported risk factors. 

Licensed indications

• For sale as a P medicine, simvastatin 10 mg at a dose of one 10 mg tablet each night, on a long-term basis is indicated to reduce the risk of a fi rst major coronary event in individuals at moderate risk of CHD, including:

1. men aged 55–70, with or without risk factors
2. men aged 45–54, with one or more listed risk factors
3. postmenopausal women aged 55–70, with one or more risk factors.

• The risk factors are:

1. smoker – currently or within the last 5 years
2. family history of CHD – father or a brother had a heart attack before age 55, or mother or a sister before age 65
3. overweight or obese – body mass index above 25, or waist measurement greater than 100 cm (40 in) in men or 87.5 cm (35 in) in women
4. South-Asian family origin.

Licensing restrictions
Over-the-counter simvastatin is considered not suitable in the following circumstances for the following people, who should be referred to a doctor:

• men over 55 years with a family history of CHD and at least one other risk factor, as above
• people with, or reporting, any symptoms that might suggest: any cardiovascular, cerebrovascular or peripheral vascular disorder; liver disease or history of abnormal liver function tests; renal impairment; hypothyroidism; myopathy or family history of muscle disorders
• people with a known fasting LDL-cholesterol level of 5.5 mmol/l or above (cholesterol testing before sale is not a licensing requirement but is recommended as good practice by the Royal Pharmaceutical Society of Great Britain (RPSGB))
• people whose blood pressure is known and within the range for referral in accordance with RPSGB practice guidance (blood pressure testing before sale is not a licensing requirement but is recommended as good practice by the RPSGB)
• men who consume more than 4 units and women who consume more than 3 units of alcohol per day, and people who drink more than 1 litre grapefruit juice per day
• people who have suffered previous side-effects or allergy when taking cholesterol-lowering medication.

RPSGB good practice recommendations
In addition to the licensing conditions, the RPSGB recommends the following good-practice measures in association with the over-the-counter sale of simvastatin:

• Pharmacists should be involved in all initial sales but subsequent sales may be delegated to appropriately trained medicines counter assistants.
• Where possible, sales should be recorded in the patient’s medication record.
• Lifestyle advice to reduce the risk of CHD should be given to purchasers.
• Pharmacists should liaise with local general practitioners and primary-care organisations to fi t in with local policies on management of CHD risk and prescribing of statins; they should encourage purchasers to inform their general practitioner that they are taking simvastatin.
• Pharmacists should monitor people who buy simvastatin at least once a year for adverse effects, interactions, changes in risk factors and blood cholesterol levels.
• Adverse effects
• Simvastatin is generally well tolerated and side-effects are usually rare, mild and transient.
• Myopathy and rhabdomyolisis, characterised by generalised muscle pain, tenderness or weakness, have been reported very rarely.
• Liver dysfunction, gastrointestinal disturbances and hypersensitivity reactions have also been reported rarely.

Interactions

•   Simvastatin is metabolised in the liver by the P450 isoenzyme CYP3A4 and interactions can occur with drugs that inhibit this enzyme.
•   Simvastatin may also increase the anticoagulant effect of warfarin and other coumarins.
•   Drugs that can cause myopathy or rhabdomyolysis, including fi bric acid derivatives and nicotinic acid, increase the risk of developing these conditions if given in association with simvastatin.

Low-dose aspirin

• Low-dose aspirin reduces the risk of MI, increases survival in patients who have had an acute MI and reduces the risk of stroke, through inhibiting thrombus formation within coronary and cerebral blood vessels.
• The anti-infl ammatory and antithrombotic effects of aspirin depend on its ability to inactivate the enzyme cyclo-oxygenase. Platelets (thrombocytes) in the blood play an important role in the process of coagulation. Through irreversible inhibition of cyclo-oxygenase, aspirin prevents the synthesis of thromboxane A2 which promotes platelet adhesion and aggregation. Platelets cannot synthesise more thromboxane A2, which is only restored when existing platelets are replaced from the vascular endothelium. Continuous low dosing with aspirin thereby maintains thromboxane A2 at a low level.
• Antiplatelet aspirin is indicated for the secondary prevention of thrombotic cerebrovascular and cardiovascular disease, at a dose of 75 mg daily.
• Low-dose aspirin is also indicated for primary prevention of MI or stroke when the estimated 10-year cardiovascular disease risk is 20% or greater. 
• Antiplatelet aspirin therapy should only be initiated on the advice of a doctor.
• The same contraindications, cautions and interactions apply as for aspirin at analgesic doses.

Omega-3 triglycerides

• Omega-3 triglycerides are derived from fi sh oils. They contain triglycerides of omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These exert an antithrombotic effect by competing with arachidonic acid for inclusion in cyclo-oxygenase and lipoxygenase synthesis pathways, reducing platelet aggregation and decreasing platelet counts. They also lower blood cholesterol levels through reduction of very-low-density-lipoproteins. As cyclo-oxygenase inhibitors they also have anti-infl ammatory activity.
• EPA and DHA in fi  sh oil have a role in the secondary prevention of cardiovascular disease.
• Almost all products containing fi sh oils are marketed as food supplements, not medicines.