OTC statins: will they deliver the goods?
Should patients at moderate risk
of coronary vascular disease self-medicate? Expert opinion remains divided Alisdair Stirling reports
Simvastatin 10mg (Zocor Heart Pro) could be marketed to around five million people if it is reclassified in the coming months. The back-of-the-envelope figure supplied by Johnson and Johnson/ MSD Consumer Pharmaceuticals, the partnership seeking the switch, indicates the potential clinical and financial impact of the move.
Of the four million or so patients currently eligible for prescribed statins under the national service framework for coronary heart disease around 1.5 million are being treated, saving according to Department of Health figures some 6,700 lives a year.
But, as all GPs know from their prescribing budgets, this comes at a considerable cost.
Having spent some £550 million on statins last year the NHS will spend
another £700 million this year, with the cost potentially spiralling to a colossal
£2.1 billion a year by the end of the decade, Treasury-commissioned figures suggest1.
And despite having backed their commitment to statin prescribing with extra cash thus far, ministers are aware of the growing cost burden on the NHS.
So to what extent is the proposed POM to P switch an attempt to ring-fence NHS spending on statins as some critics have claimed and to what extent is there a clear clinical rationale behind it?
The Government's argument for backing the plan under which pharmacists would identify moderate-risk patients is summed up by Professor Rory Collins,
co-director of the Clinical Trials Service Unit at the University of Oxford: 'Magnitude of benefit [from statins] depends on magnitude of risk. And moderate-risk individuals do benefit as well as those at high risk.'
Professor Collins, an adviser to the Committee on Safety of Medicines which approved the consultation exercise on simvastatin, is equally clear about the specifics: 'At 10mg dose you'd expect an average 1mmol/l reduction in LDL-cholesterol over five years translating to a reduction in risk of at least a quarter.'
Professor Collins' claims echoed by the CSM in the Medicines and Healthcare products Regulatory Agency consultation document issued to more than 250 stakeholders last month are based on extrapolation from a swathe of landmark statins studies.
Chief among these, according to the department, are the West of Scotland Coronary Prevention Study (WOSCOPS), the US Air Force/Texas Coronary Prevention Study (AF/TEXCAPS) and Professor Collins's Oxford unit's Heart Protection Study (HPS).
WOSCOPS was a five-year double-blind placebo-controlled trial of pravastatin 40mg daily in 6,595 men between the ages of 45 and 64 who had elevated LDL-C levels in the range 4-6mmol/l. Results published in the New England Journal of Medicine in 1995 showed pravastatin rapidly
reduced the men's risk of a first heart attack by 31 per cent.
AF/TEXCAPS randomised 5,608 men and 997 women with average LDL-C levels of 3.8mmol/l to either placebo or lovastatin 20 to 40mg daily. Results published in the Journal of the American Medical Association in 1998 suggested after a five-year follow-up lovastatin cut the risk of combined unstable angina, fatal and non-fatal myocardial infarction and sudden cardiac death by 36 per cent.
The HPS, published in The Lancet and the BMJ in 2002, randomly allocated 20,536 adults aged 40 to 80 with coronary disease, other occlusive arterial disease or diabetes to receive 40mg simvastatin daily or placebo. Results showed simvastatin cut the risk of heart attack, stroke or revascularisation by 24 per cent. And after allowing for non-compliance, the researchers said actual use of the regimen 'would probably reduce these rates by about a third'.
Crucially, the study also suggested the size of the five-year benefit depended chiefly on individuals' overall risk of major vascular events, rather than on their blood lipid concentrations alone.
Taken together, the results of the studies suggest, as the MHRA puts it in the
consultation document: 'The level of absolute risk-reduction depends on the starting level of risk.'
While no specific clinical trials have been conducted with simvastatin 10mg in this particular patient population it is reasonable to assume these benefits would also apply to this group of people given that the effect of lowering LDL-C by simvastatin is consistent between populations and the relation of LDL-C to risk is linear.
And despite cases of myopathy, rhabdomyolosis and biochemical liver function abnormalities associated with simvastatin, the CSM is also satisfied with the drug's safety record. Side-effects are reportedly rare in the clinical trials at higher doses and are seen as likely to be even lower at the 10mg dose.
The committee's chair, Professor Gordon Duff, said: 'Statins have been available in the UK for the last 14 years and their safety as a class is well established.' Safety would continue to monitored under the MHRA/CSM's Yellow Card scheme under the proposals for the switch, he added.
Professor Shah Ebrahim, professor of epidemiology of ageing at the University of Bristol, editor of the Cochrane Heart Group and member of the external reference group for the NSF for CHD, accepts that statins are safe and effective.
But he believes that is not sufficient argument for the drugs to be made available over the counter. 'CHD is a multifactorial disease of which raised blood cholesterol is just one factor. There is a danger that patients with several risk factors who go on to statins might carry on smoking and downing several litres of lard a week,' he says.
Professor Ebrahim echoes the views of GPs who have criticised the POM to P switch: 'The likelihood is that wrong people will take them. We haven't got all those with established CHD on to aspirins yet,' he adds.
Professor Ebrahim says he would prefer to see statins used in a general practice setting where GPs could help patients assess their risk and encourage dialogue over treatment.
Another potential pitfall of the switch is that long-term compliance with statin
self-medication will be essential for any public health gains as studies show benefits during the first year of treatment are minimal.
The MHRA consultation document includes guidelines for pharmacists for assessing patients' risk and calls for pharmacists to have training that would cover repeat purchases. Patients could also be on the receiving end of direct advertising if new rules being considered by the Proprietary Association of Great Britain are adopted.
Professor John Betteridge, consultant physician at University College Hospital in London and an expert in lipid-lowering therapy, says he is 'warming' to the notion of patients taking more responsibility for their own health as long as they are properly supervised and supported.
'It's not going to be the same as seeing a doctor, but if the set-up's right then I think it'll work. If someone's going to make the effort to take statins, they'll make the effort to take care of other things,' he adds.
Professor Betteridge said that even if patients self-medicating with statins did neglect other CHD risk factors they
would still see a benefit from the statins alone a claim supported by data from the Heart Protection Study that suggests
the benefits of simvastatin are additional
to those of other cardioprotective treatments.
Dr Mark Davis, a GP in Leeds and also a member of the external reference group for the NSF on CHD, supports the switch but also emphasises the need for supervision.
'It should be part of a package. One would hope that pharmacists will give support to patients on smoking, diet and so on,' he says.
The Government is aware that price will be a crucial factor in uptake. Simvastatin currently costs £18.03 for 28 days' supply. But increasing availability of generic versions over the next few years could cut the cost of statins to the consumer and the NHS considerably.
And as both Professor Collins and Professor Betteridge point out, many patients habitually spend a lot of money on vitamins over the counter without any real evidence of efficacy.
Wanless D. Securing Our Future Health: Taking A Long-Term View. London: HM Treasury, 2002
What going over the counter will mean
Under the NSF for CHD, patients with a 30 per cent 10-year risk of CHD should be prescribed statins. It is expected that this risk threshold will
be lowered to cover those with a 15 per cent or more 10-year risk in
Joint Society guidelines due next year.
Under the proposed POM to P switch, simvastatin 10mg would be available over the counter to those at moderate risk of CHD. This would include men aged 55 and over. Also men aged 45 to 55 and women over 55 who have one or more of the following risk factors:
· Family history of CHD in a first-degree relative; CHD in male first-degree relative below 55 years or female first-degree relative below 65 years
· Smoker (is currently a smoker or has been a smoker in the last 12 months)
· Overweight (BMI greater than 25kg/m2 and/or truncal obesity (waist 40 inches or 102cm in men; 35 inches or 88cm in women)
· South Asian ethnicity (Indian subcontinent)