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Analysis: Is primary prevention with statins worth the effort?

With a new QOF indicator designed to increase the proportion of hypertensive patients prescribed a statin and Government plans to radically expand the NHS Health Checks programme, GPs look set for a big increase in the number of patients who are taking statins for primary prevention.

But a rift is opening up, with some GPs warning that the drive is over-medicalising patients.

One analysis of the major trial evidence being prepared for publication concludes that even high-risk patients taking statins only gain an average of around 14 extra days of life. Does the evidence for primary prevention need to be re-evaluated?

Dr Malcolm Kendrick, a GP in Macclesfield, Cheshire, and a high-profile statins critic, certainly thinks it does. He presented his as-yet-unpublished analysis of the evidence at a debate on primary prevention at the Pulse Live conference last month, claiming the benefits have been vastly overblown by the way trials have been conducted and reported.

‘I don’t look at numbers needed to treat, relative risks, combined endpoints or effect on cardiovascular disease or coronary heart disease alone,’ says Dr Kendrick, a GPC member and a former education adviser to the European Society of Cardiology. ‘I look at the impact on average life expectancy - if you are going to give people medication for years and years, this is what matters.’

His analysis of data from the landmark Heart Protection Study shows that even among the high-risk patients in the study, use of statins compared to placebo resulted in 1.8% of patients living an average of just four months longer. For the other 98.2%, the statin had no impact on life expectancy.

Statins in primary prevention do more harm than good and we should stop prescribing them.

Dr Malcolm Kendrick

‘This means that the average increase in life expectancy after five years is 14 days,’ says Dr Kendrick. ‘When I ask other doctors how much longer they think you live if you take a statin for years, most say five years, 10 years. The reality is it’s days.’

Meanwhile, the latest evidence suggests around 17% of those on statins will experience adverse effects that affect their quality of life, Dr Kendrick says: ‘Impotence, cognitive deficit, anger and irritation; these are all side-effects of statins.’

He concludes: ‘Statins in primary prevention do more harm than good and we should stop prescribing them.’

Population benefit

For many GPs, it is wrestling with the knowledge that so many of their patients will not individually benefit from taking a statin that is the main concern.

Glasgow GP Dr Des Spence, a long-time critic of the marketing activity of the pharmaceutical industry, says: ‘The annual NNT to prevent vascular events is 500, but to prevent vascular death the NNT is in the order of 1,250 in a population of 60 and over.

‘So the benefits are seen on a population basis, the individuals having no benefit despite years of medication. Also, these recent meta-analyses are of data from 20 years ago. Since then the background incidence has halved, potentially meaning the reported NNT has doubled.’

He adds: ‘I’m not saying statins don’t work; they may have a role in secondary prevention - but we have to be very clear with people when we start them on statins [for primary prevention] that the direct benefits are going to be negligible.’

A lowered threshold?

Both GP sceptics are very much outside the mainstream of scientific opinion. The consensus is that the weight of evidence points towards a positive benefit for statins in primary prevention.

A recent meta-analysis even suggested that the 20% cardiovascular risk threshold for initiating statins should be lowered - something that NICE may look at in its ongoing update of its lipid modification guideline, due out next year.

The Cholesterol Treatment Trialists’ Collaboration meta-analysis of 22 trials showed that people with the lowest five-year predicted risk of major vascular events at baseline had a significantly reduced risk of major vascular events with statin treatment. In people with a 5% to 10% five-year risk at baseline, relative risk was lowered by 31% for every 1.0mmol/l reduction in LDL-cholesterol.

An updated Cochrane review published in January has added further supporting evidence, showing statin treatment resulted in 14% and 25% relative reductions in all-cause mortality and combined fatal and non-fatal coronary heart disease respectively, in a largely primary prevention population.

Despite this, some GPs are still concerned about the impact of the new QOF target for primary prevention introduced this year. The indicator requires GPs to report the percentage of patients aged 30 to 74 years with a new diagnosis of hypertension and a 20% or higher 10-year risk of CVD who are on statins.

Dr Martin Brunet, a GP in Guildford and programme director of the Guildford GPVTS, says there is not enough room for patient choice in guidelines or the QOF, especially when treating patients ‘in the middle’ for whom the balance of risk to benefit is least clear.

A middle ground

‘There should be a “grey area” in the middle talking about the pros and cons and how it depends on the individual patient - where patient choice should be at the forefront, with the doctor providing the information and helping the patient make the right choice for them,’ he says.

Dr Brunet recounts a recent roleplay he conducted with final-year GP trainees, which revealed that 80% would not wish to comply with the new QOF target if they were the patient, based on NNTs for primary prevention with statins.

‘This is despite the fact most of them would have no qualms about recommending treatment at this level to their patients,’ says Dr Brunet.

The QOF indicator could increase inappropriate statin use, he warns: ‘Exception reporting feels like a big deal and GPs don’t use it very often, which means in practice patients might not be able to make an informed choice, because GPs might put them under pressure to take extra treatment without having that full discussion with them.’

The Government is also planning to radically expand the NHS Health Checks programme to all 15 million eligible people by 2016; as set out in its CVD strategy published in March.

Provided we use the newer drugs, you can actually see the benefit

Professor Kausik Ray

Professor Kausik Ray, professor of cardiovascular prevention at St George’s Hospital in London and a member of the European Society of Cardiology prevention working group, says the increasing availability of generic versions of more potent statins - atorvastatin came off patent last year - will increase the benefit in populations with a low background event rate and make primary prevention more cost-effective.

He says: ‘Provided we use the newer drugs that are becoming available as generics, you can actually see the benefit in lower-risk populations.’

He says that many events occur in patients with a risk of lower than 20% and that the approach of using lifetime risk - tipped for inclusion in the long-awaited JBS3 guidelines - could provide better targeting of treatment.

At the Pulse Live debate, Dr Terry McCormack, a GP in Whitby and a cardiology GPSI, likened the use of statins to having crash barriers on motorways: ‘About 57% of money goes into inpatient medical care - that is shutting the stable door after the horse has bolted. It is worth remembering that 25% of people are going to die of their first myocardial infarction - and we just don’t know who those people are going to be.’

How the stats stack up: two views

Dr Malcolm Kendrick

‘Even among high-risk patients, taking a statin for five years results in 1.8% of people living just four months longer on average - but for 98.2% the statin has no effect on life expectancy.

‘This means that the average increase in life expectancy from taking a statin is 14 days. In other words, there is a roughly one-in-50 chance that you will be one of the people who will live for four months extra if you take this medication.

‘But about 17% of those who take a statin will suffer side-effects that affect their quality of life.’

Dr Terry McCormack

‘25% of people will die of their first heart attack - but we don’t know in advance who they are going to be, which is why prevention is so important. The latest evidence shows that in all aspects, the benefits of statins outweigh risks, even among those at lowest risk of a vascular event. For example, the CTTC meta-analysis published last year in The Lancet showed that even among people with a five-year CVD risk below 10%, every 1mmol/l reduction in LDL-cholesterol meant 11 fewer major vascular events per 1,000 patients over five years.’



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