Use of statins

Introduction

Treatment with statins (HMG co-A reductase inhibitors) lowers serum cholesterol substantially and has been shown to reduce myocardial infarction, coronary deaths and overall mortality in recent controlled trials. The purpose of this statement is to help doctors to set priorities for treatment with statins. It is based upon the best evidence available at the moment on clinical effectiveness, cost-effectiveness and long-term safety. It is not intended to replace or override clinical judgement in individual cases. It is also important to take note of local policies where they exist. The aim is to give general advice on those individuals who will benefit from statin treatment, and which groups of patients will benefit most and should have priority for statin treatment.

Who should be considered for treatment with statins?

Before considering the use of statins, other methods to reduce the risk of coronary heart disease (CHD) should be instigated :
- advice and help on stopping smoking;
- dietary advice, particularly to control weight and lower lipids
- advice on regular physical activity;
- control of hypertension ;
- other pharmacological measures, such as aspirin therapy, where appropriate.
Cholesterol-lowering treatment should be targeted at those at high risk of major coronary events, not high cholesterol alone . The average serum cholesterol is high in the UK population, and it might be argued that statins could be administered with advantage to a large proportion of British adults. However serum cholesterol is, by itself, a weak predictor of coronary risk in individuals and it is important that statins, which are expensive, are not prescribed for subjects who have a low coronary risk despite a high serum cholesterol. Furthermore the evidence for the safety of statins comes from randomised controlled trials of only 5-6 years' duration. The balance of benefit and risk has not been determined for treatment of longer duration. This is unlikely to be important when treating those at high risk of major coronary events - we suggest 3% per year (30% over 10 years) or more - but is more significant when considering treatment of people with a relatively low CHD risk.

Secondary Prevention:

The first priority for lipid lowering therapy with a statin is patients who have had a myocardial infarction . These patients have a very high CHD risk, and treatment is indicated when the total cholesterol level is as low as 4.8 mmol/l (or Low Density Lipoprotein (LDL) as low as 3.2 mmol/l, if measured).
The second priority for lipid lowering therapy is patients with angina or other clinically overt atherosclerotic disease who have total cholesterol of 5.5 mmol/l or more (or LDL 3.7 mmol/l or more, if measured). This includes patients with peripheral vascular or symptomatic carotid disease or who have had a bypass graft or angioplasty. These patients have a risk of major coronary events which averages approximately 3% a year.
Together, these two priority groups encompass about 4.8% of the population aged 35-69 (5.9% of men and 3.6% of women).

Primary Prevention:

The third priority is treatment of people without clinically apparent vascular disease but who nevertheless have a high risk of developing overt CHD , equivalent to those requiring secondary prevention (ie a risk of major CHD events of 3% per year or more), and have a total cholesterol of 5.5 mmol/l or more (or LDL 3.7 mmol/l or more) based on the average of at least two measurements taken several weeks apart. People may have this level of risk because of a combination of other CHD risk factors, particularly diabetes or hypertension. (NB People with familial hyperlipidaemia are at high risk of CHD.)
This group for primary prevention encompasses a further 3.4% of the population aged 35-69 (5.7% of men and 0.4% of women).
Few trials have included people over the age of 70. There is little trial evidence of benefit or harm from starting statin treatment in people over the age of 70 for the primary prevention of CHD.
Treatment of people free of vascular disease with a risk of developing overt CHD of less than 3% a year and a total cholesterol of 5.5 mmol/l or more (or LDL 3.7 mmol/l or more) would entail treating a high proportion of adults. At present cost-effectiveness is low.
Formal estimation of CHD risk is essential when identifying subjects for primary prevention of CHD. The Sheffield table (enclosed) is a simple method which identifies those people without CHD who should have their cholesterol measured. It also identifies those with an annual CHD event risk of approximately 3%.

Statin treatment

Currently there is evidence that two statins, simvastatin and pravastatin, reduce overall mortality and have proven long-term safety.
Treatment should be started at a low dose and increased as necessary to reduce total cholesterol to 5.0 mmol/l, or by 30% in those high risk patients (eg with a previous myocardial infarction) who have serum cholesterol below 6.3mmo1/1 before starting treatment.

Comparative efficacy of statins

Drug	Dose	% TC reduction	%LDL reduction
Pravastatin	10mg	13%	19%
	20mg	18%	25%
	40mg	24%	27%
Simvastatin	10mg	21%	28%
	20mg	26%	35%
	40mg	30%	40%
Atorvastatin	10mg	28%	41%
	20mg	35%	44%
	40mg	40%	50%
Cerivastatin	l00mcg		22%
	200mcg		28%
	300mcg		31%
	400mcg	26%
Fluvastatin	20mg		19%
Fluvastatin	40mg		25%

Statin manager
Hyperlipidaemia protocol
Testing pitfalls and summary of guidance in lipid management
Practice formulary: statins
FATS3 - A district wide strategy for the use of cholesterol lowering drugs in Newcastle and North Tyneside
FATS3 – additional guidance
Considering statins - sharing risk

Original source: Department of Health - May 1997, with additions