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Should we use statins for primary prevention of cardiovascular disease?

Why start to prevent a cardiovascular event only when a patient has had one, asks Dr George Kassianos. However, Dr Matt Hughes argues we need better data.

Nobody doubts that statins play an important role in secondary prevention. Why should it be different for primary prevention? Why should the journey to prevention of cardiovascular disease start at the coronary care unit?

We have these concepts of ‘primary' and ‘secondary' prevention, but in fact, atherosclerosis starts early and progresses continually throughout life. If the individual has an event, we do something about it. On occasions we call our treatment ‘aggressive', but it comes too late to prevent that first event – although hopefully it will prevent the next one. Surely, this isn't how to practise preventive medicine? What our patients want is the prevention of that first event. To achieve this, there has to be a change of attitude. Not just in the medical profession, but also among organisations such as NICE. We seem to be preoccupied with fire fighting instead of fire prevention.

How should we prevent CVD? Well, the INTERHEART study shows nine modifiable risk factors that account for more than 90% of initial acute myocardial infarction risk.1 The strongest is cholesterol level, then smoking, psychosocial events, hypertension, abdominal obesity, diabetes, unhealthy diet, excess alcohol and lack of exercise. Raised cholesterol is strongly related to coronary heart disease, moderately related to peripheral arterial disease, modestly related to ischaemic stroke and unrelated to haemorrhagic stroke.

We treat raised cholesterol non-pharmacologically until the patient's 10-year CVD risk is 20%. We allow CVD to progress when we could have done a lot more. There is evidence that a huge benefit can be derived in patients with a 10-year CVD risk at and below 10%, as shown in the JUPITER study. In this primary prevention study of rosuvastatin against placebo, patients did not have raised cholesterol; their LDL was below 3.4mmol/l but their C-reactive protein was greater than or equal to 2mg/l.2 They had no history of heart attack or stroke and still, within a year and a half, those on rosuvastatin derived a relative risk reduction of 44% for a first major cardiovascular event.

With the price of one year's simvastatin at less than a good bottle of wine, can we afford to turn a blind eye to pharmacological management of cholesterol until CVD is established? Surely not.

Dr George Kassianos is a GP in Bracknell, Berkshire, and a fellow of the European Society of Cardiology




One of the best reasons for us to reconsider how we use statins in patients without pre-existing cardiovascular disease came in a study in the Archives of Internal Medicine a few months ago.1 It provided arguably the most complete meta-analysis of the data on lipid lowering in a high-risk population.

Limiting the analysis to patients without existing coronary heart disease – but at high risk of it – was critical because studies that have included both groups may appear to show across-the-board benefit, when in fact the benefit is limited to those with existing conditions.

The patients in their analysis saw their LDL-cholesterol levels drop from an average 3.6mmol/l to 2.5mmol/l, which makes them pretty representative of the patients we see in our surgeries. But the results showed that the use of statins over an average treatment period of 3.7 years was not associated with a statistically significant reduction in all-cause mortality.

The sample size – and the number of events – was large enough to detect a clinically meaningful effect. But they simply couldn't find one.

In the same issue there was also a critical analysis of JUPITER – a randomised, double-blind, placebo-controlled study sponsored by AstraZeneca investigating the use of rosuvastatin in primary prevention.2

JUPITER is unique in that it reported a substantial decrease in the risk of CVD among patients without CHD and with normal or low cholesterol levels. This result has been widely used to seal the deal on the argument that statins have a big impact on cutting cardiovascular mortality and morbidity in high-risk patients. But the authors of the new analysis criticised the study – particularly the decision to stop the trial early after just under two years. There is a suggestion that prematurely terminated trials can show implausibly large estimates of treatment benefits that later regress to the mean on longer follow-up.

I fully accept that a safe, effective treatment that cut mortality in patients at high risk of CVD would be very exciting indeed – most patients who have major coronary events haven't been diagnosed with known disease.

Those who support lipid lowering for primary prevention insist that benefit will become obvious the longer these patients take statins. But I say we need to make decisions based on the evidence we have now to justify the advice we give patients. So what do we really know about primary coronary prevention? One of the things we can say – based on one of the best analyses in a true primary prevention population – is that the benefit is, at best, very small.

Dr Matt Hughes is a GP and hospital practitioner in cardiology in Cardiff

yes no Statins