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GPs fear smoking advice will alienate

Dr George Kassianos makes an evidence-based argument against the latest NICE draft appraisal on statins and advises what GPs should do

in light of the controversy

Lipid-modifying therapy is now recommended for nearly all patients at increased risk of cardiovascular disease, and statins represent the most important class of cholesterol-lowering drugs.

As more and more clinical trial data supporting the use of statins has become available, prescribing and spending on statins has increased significantly. In fact, more is now spent on lipid-regulating therapies than any other class of cardiovascular drug.

Prescribing and spending have both risen by around 250 per cent over the last five years (6.4 million items and £184.7 million, quarter to December 2003)1.

But the situation has become increasingly complicated for GPs who are now faced by a raft of conflicting guidelines culminating in the controversial draft NICE guidance published last month.

The differing guidance

·NICE: draft appraisal limits the use of statins to patients under the age of 75 and who are at a 20 per cent 10-year CHD risk (equal to 26.7 per cent 10-year CVD risk) or higher. For patients over 75, NICE says statins should not be routinely used and that the decision to use them should be made on a case-by-case basis.

·The latest British Hypertension Society

IV guidelines (2004) set an LDL-C target of <3mmol and="" a="" total="" cholesterol="" of=""><4mmol in="" high-risk="" individuals.="" the="" bhs="" concludes:="" 'it="" seems="" reasonable,="" in="" the="" interests="" of="" simplicity,="" to="" treat="" with="" a="" statin="" all="" those="" patients="" at="" least="" up="" to="" age="" 80="" with="" a="" total="" cholesterol="">3.5mmol/L, who have an estimated 10-year CVD risk of 20 per cent or more'.

·The forthcoming Joint British Societies recommendations, soon to be published, will almost certainly recommend the use of statins for those at a 20 per cent 10-year CVD risk, which is equivalent to a 15 per cent 10-year CHD risk.

Guidance vs evidence

The NICE recommendations appear to contradict mounting evidence from a large number of good-quality lipid-lowering trials such as ASCOT, GREACE, WOSCOPS and HPS. These show that lower LDL-C levels are associated with a reduced cardiovascular risk and that differing statins have differing safety and efficacy profiles.

Further, there is overwhelming evidence to suggest the benefit of prescribing statins to patients over the age of 75, including the HPS, PROSPER and the ASCOT trials.

The JBS predicted recommendation is lower than the figure recommended by the latest appraisal from NICE, which advocates statins for those at a 20 per cent 10-year risk of CHD, that is a 26.7 per cent 10-year risk for CVD!

Treating those with a 20 per cent 10-year risk of CHD will result in around 1.5 million more adults in England and Wales becoming eligible for statin therapy, when compared with the year 2000 NSF on CHD that recommends statins for those at a 30 per cent 10-year CHD risk.

However, it still means that many who would benefit from statin treatment will not be eligible and appears to contradict NICE's own economic analysis that indicates statins would be cost-effective at a 15 per cent risk or lower.

Cost must not drive treatment choices

It is perhaps the cost implication that has had the greatest influence on those responsible for drawing up the recent, much-criticised NICE appraisal consultation document on the use of statins for the primary and secondary prevention of coronary heart disease.

This draft document seems to suggest that cost of treatment should be the primary consideration when determining which statin should be initiated. The consultation document states: 'Therapy should be initiated with the drug with the lowest acquisition cost.'

The NICE consultation document on statins is a backward step. It concentrates only on CHD when we should be looking at the whole cardiovascular system as well as the various ethnic minority groups in the UK. It reintroduces ageism, something that we thought we had abolished for good. Further, it contradicts other guidelines such as the BHS IV 2004 guidelines on when to pharmacologically modify lipids in primary prevention.

In spite of all the evidence that lipid lowering reduces the risk of cardiovascular generally and in particular coronary events, guidelines for the use of statins are still not well adhered to. A recent report, HEART UK6, shows up to 50 per cent of patients do not even achieve the new GMS target of 5.0mmol/L, despite being treated with a statin.

The report adds that statins are not always used correctly and are still not initiated at evidence-based doses. Once we have the national QOF framework clinical indicators data published we shall know whether the situation in this country has changed for the better.

Statins in clinical practice

Despite the fact that guidelines advocate ever-lower targets for LDL-C, GPs interested in treatment efficacy rather than cost issues alone have five

statins to choose from. These statins differ considerably one from another and the differences were highlighted by the STELLAR study

(Statin Therapies for Elevated Lipid Levels compared across doses to Rosuvastatin)5. In the

first year of nGMS we saw a rash for achieving the total cholesterol target of 5mmol/L or below.

To achieve this in the available few months, we had to review the efficacy of each of the statins we use in our practices, choosing the one with the greatest lipid-modifying properties.

My approach to prescribing statins

I take an approach adapted from BHS IV guidelines.

1 Calculate the CHD risk ­

primary prevention

·Use the Joint British Societies coronary risk prediction chart (at the back of the BNF) or the coronary risk calculator on your practice computer system.

·Use the initial (pre-treatment) blood pressure reading and the first (pre-treatment) total cholesterol and HDL-C.

·Smoking reflects lifetime exposure to tobacco (consider an individual who has given up smoking during the last five years as a 'smoker').

2 Ask 'when is the 10-year CHD risk higher

than indicated in the charts?'

·Approaching the next age category in the charts

·Family history of CHD in first-degree relative male <55y><65 (multiply="" risk="" by="">

·Women with premature menopause

·Raised triglycerides

·Impaired fasting glycaemia (fasting blood glucose 6.1-6.9mmol/L)

·Individuals from ethnic groups (multiply risk by 1.5 if from the Indian subcontinent)

3 Convert 10-year CHD risk

to 10-year CVD risk

·Calculate the 10-year CHD risk, multiply by 4/3 and this will give you the 10-year CVD risk

Example: 10-year 15% CHD x 4/3 = 20% 10-year CVD risk

4 Use a

statin for

i) Primary prevention

·10-year CVD risk =20% (CHD =15%)

ii) Type 2 diabetes ('coronary equivalents' ­ secondary prevention)

·> 50 years of age or

·diagnosis made >10 years ago

iii) Type 1 diabetes

·> 40 years of age: treat as per type 2 diabetes

·< 40="" years="" of="" age:="" consider="" the="" individual="">

5Target cholesterol in

patients with diabetes

·Total cholesterol <4mmol (audit="" standard=""><5) or="" reduce="" by="" at="" least="">

·LDL-C: <2 mmol/l="" (audit="" standard=""><3) or="" reduce="" by="" at="" least="">

George Kassianos is a GP in Bracknell, Berkshire, and a member of the British Hypertension Society and Primary Care Cardiology Society ­ he represented the RCGP in the development of the NICE guidelines for type 1 diabetes

The evidence supporting wider statin use

The 4S study

More than 10 years ago, the 4S study (Scandinavian Simvastatin Survival Study) showed that simvastatin significantly reduced the risk of major coronary events in all quartiles of baseline total, and LDL cholesterol, by a similar amount in each quartile2.

ASCOT (The Anglo-Scandinavian Cardiac Outcomes Trial)

and HPS (Heart Protection Study). These studies confirmed that a 1mmol/L reduction in total or LDL cholesterol reduces the risk of coronary or cardiovascular events by about a quarter and that these benefits are seen, regardless of the age or gender of the patient.

PROVE-IT (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infraction)3

This study reflects a growing body of evidence that suggests the lower the

LDL-C the better. The latest European guidelines (2004) reflect this, setting LDL targets at <3mmol in="" non-high="" risk="" individuals="" and=""><2.5mmol in="" high-risk="">

CARDS (Collaborative Atorvastatin Diabetes Study)

Data from the recent CARDS study has also shown that lowering LDL-C with atorvastatin, even in those who do not have high LDL-C, can cut risks of cardiovascular events in patients with type 2 diabetes4. The CARDS data is particularly important as it highlights the need to assess patients' global cardiovascular risk before initiating therapy.



2 Scandinavian Simvastatin Survival Study. Randomised trial of cholesterol lowering in 4,444 patients with coronary heart disease. Lancet 1994; 344:1383-9

3 Cannon CP et al. Design of the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in

Myocardial Infarction (PROVE- IT)-TIMI 22 Trial.

Am J Cardiol 2002; 89:860-1

4 Colhoun HM et al. Primary prevention of cardiovascular disease in type 2 diabetes in the Collaborative Atorvastatin Diabetes

Study (CARDS) multicentre, placebo-controlled trial.

Lancet 2004; 364:641-2

5 Jones PH et al for the STELLAR study group. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin,

simvastatin and pravastatin across doses (STELLAR Trial).

Am J Cardiol 2003; 92: 152-60.

6 HEART UK ­ 'The forgotten 50'

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