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RESEARCH: Heart Protection Study Collaborative Lifetime cost effectiveness of simvastatin in a range of risk groups and age groups derived from a randomised trial of 20 536 people BMJ 2006; 333: 1145 [Abstract] [Full text]

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300 years of tablet taking

Richard G Richards   (22 November 2006)

What is the most cost-effective dose of Simvastatin ?

Leslie S Lewis   (2 December 2006)

Common miracles

Neha S. Godre   (3 December 2006)

Flawed study?

Jeffrey R johnstone   (3 December 2006)

Conclusion misleading

john sharvill   (4 December 2006)

Re: Conclusion misleading

L S Lewis   (6 December 2006)

Simvastatin Even Cheaper And More Cost Effective Than Suggested

John S Ashcroft   (6 December 2006)

Competing interests

Jeffrey R Johnstone   (7 December 2006)

Marginal vs average costs

Adam Jacobs   (9 December 2006)

Re: Marginal vs average costs

L S Lewis   (11 December 2006)

The evidence mounts further yet we are still failing to provide basic care to those who need it most

Beck Taylor, Andrew Rouse, Consultant in Public Health   (19 December 2006)

Re: The evidence mounts further yet we are still failing to provide basic care to those who need it most

L S Lewis   (20 December 2006)

Agreement between PH and GPs?

Richard G Richards   (21 December 2006)

We must get the basics right

Beck Taylor   (22 December 2006)

300 years of tablet taking 22 November 2006
Richard G Richards, consultant in public health 65 North Gate, Newark, NG24 1HD Send response to journal: Re: 300 years of tablet taking	That simvastatin, now off patent, is cost effective even at 5% five year risk is not surprising. For me as a population physician this is a very attractive intervention, but what about the individual making an informed choice? At 1% annual risk the annual risk reduction is 0.33%, a NNT of 300: that means there needs to be 300 patient years of treatment for one event to be avoided. For the individual that surely must equate to 300 years of daily pill taking. At 85 (and most, if not all 85 year olds are at 5% 5 year risk) life expectancy is 5-6 years so 300 years does not seem to be meaningful. Even at 35 years (life expectancy about 45 years) there needs to be 6-7 lifetimes of daily pill taking for one event to be avoided. If I take a pill daily its likely to be low-dose aspirin. Otherwise I'll stick to red wine and olive oil. Competing interests: None declared
What is the most cost-effective dose of Simvastatin ? 2 December 2006
Leslie S Lewis, General Practitioner Surgery, Newport, Pembrokeshire, SA42 0TJ Send response to journal: Re: What is the most cost-effective dose of Simvastatin ?	Dear Sir,   In their impressive paper, the Heart protection study group convincingly shows that prescription of Simvastatin, which priced in 2005 at £4.87,  is much more cost-effective than previously imagined.  This finding is largely due to the dramatic price reduction in generic Simvastatin, which has now reached £4.23 for 28x40mg.   HPS however persists in its one-size-fits-all preference for the 40mg dose.   The 10mg dose costs £1.81 and would allow more than twice as many people to be treated.   Given the flattened dose-response curve, we know that the first 10mg gives 80% of the cholesterol-lowering effect of 40mg.   The current NICE Guidance on STATIN suggests that anyone with a 20% or more TEN-year risk of CVD, should be on (Simva-)statin.   HPSG’s Table 6 , when redrawn to emphasise net savings at TEN-year risks, concurs with NICE guidance – which would SAVE the NHS considerable costs.   But what dose of Simvastatin is optimal ?? .   Might it be even more advantageous to give 10mg Simvastatin to more than twice as many patients ?    Urgent work is needed on the dose-benefit question.   Table 6 Cost effectiveness of full compliance with lifetime use of generic 40 mg simvastatin daily projected beyond the population of the heart protection study     TEN- year risk of CVD –  NICE recommends Statin at 20% 10% 20% 40% 80% Cost (£) per life year gained Age at start (years):    35 450* –360* –1070* –1610*  45 330* –360 –940 –1240  55 400* –210 –680 –830  65 660* 50 –380 –450  75 1180* 450 –40 –110  85 2460* 1280* 490* 310* Cost (£) per quality adjusted life year gained Age at start (years):    35 580* –460* –1370* –2060*  45 430* –480 –1210 –1600  55 550* –280 –900 –1070  65 930* 70 –510 –590  75 1740* 650 –50 –140  85 3740* 1870* 690* 420* Yours sincerely, Dr L S Lewis,  Surgery, Newport, Pembrokeshire   Competing interests: None declared
Common miracles 3 December 2006
Neha S. Godre, intern India Send response to journal: Re: Common miracles	Its not unusual for any drug to be involved in studies and controversies. As doctors, we all talk about masses, we all tend to generalise. But when I call simvastatin treatment cost effective, I am not harping about 3oo patient years of treatment or home remedies (?). Finally everything in medicine boils down to individualising therapy considering the patient's requirements. There are cases in plenitude where statins along with diet regulation have achieved a marked reduction in the coronary lumen obstruction. If that can obviate the need for a coronary angioplasty or a prevention, at a later stage, of coronary artery bypass grafting, why not?? Low dose aspirin is essential but no drug alone can be at the helm while managing heart diseases. So far as the dosage is concerned, do we really need to prescribe 40 mg simvastatin?? Titration of the dose is the most direct way to cost effectiveness. 10 milligram dose prescription to initiate the therapy can be considered more appropriate, I believe. Competing interests: None declared
Flawed study? 3 December 2006
Jeffrey R johnstone, Self-employed Home Send response to journal: Re: Flawed study?	This study appears to have neglected an important aspect of the Heart Protection Study on which it is based. This was not simply "a randomised placebo-controlled trial". It began with a group of 32,145 eligible volunteers. All were given a dose of 40mg simvastatin for 4 - 6 weeks. After this 11,609 were declared not suitable or withdrew. This was 36% of the study group. The great majority of these (26%) "chose not to enter the trial or did not seem likely to be compliant for 5 years". A trial which begins by eliminating those who, for whatever reason, decide not to take the drug being tested is surely of dubious value. At the very least the authors of this study of the cost effectiveness of simvastatin should have taken into account the consequences of a substantial proportion of patients refusing to take the drug. ray@iinet.com.au .l Competing interests: None declared
Conclusion misleading 4 December 2006
john sharvill, General Practitioner Deal England Send response to journal: Re: Conclusion misleading	In their conclusion The Heart Protection group state that simvastatin 40 mgm is likly to be cost saving. It may save money on cardiovascular events but as with all preventive measures that work this will lead to huge add on costs for care in later life. Whilst not a reason not to discuss and prescribe it is wrong to think it will save money.Total health costs will be dramatically increased. Competing interests: None declared
Re: Conclusion misleading 6 December 2006
L S Lewis, GP Surgery, Newport, Pembrokeshire SA42 0TJ Send response to journal: Re: Re: Conclusion misleading	The entire aim of medicine is damned by your interpretation - but thankfully, it aint necessarily so.. Saving lives from MI would lead to larger numbers of older people - who may (would) later suffer other 'degenerative' or 'age-related' diseases.. like dementia, stroke, cancer.. UNLESS we find cheap and effective treatment/prevention for those ailments too ! The holy grail is to prevent disease, and increase fullest quality life - AND then die quickly in your sleep when you are ready for it.. 'squaring-off' the life/quality curve. Dr Sam Lewis, GP Competing interests: Cure vs. Care
Simvastatin Even Cheaper And More Cost Effective Than Suggested 6 December 2006
John S Ashcroft, GP DE78ES Send response to journal: Re: Simvastatin Even Cheaper And More Cost Effective Than Suggested	The Heart Protection Study Collaborative are absolutely right to emphasis the cost effectiveness of simvastatin in the prevention of Cardiovascular Disease. Dr Roger Boyle has already "nailed his colours to the mast"(1) and called for a national programme to identify patients at high risk, and Muir Grey of the National Screening Committee has been given the task of producing the "Vascular Disease Risk Factor Assessment and Management Programme"(2), which the use of statins will be an integral part. However the authors still underestimate the cost effectiveness of simvastain by using the drug tariff price as a reference price. As I have previously stated in this journal, the true cost of simvastatin to the NHS is close to the pharmacists' purchase price(3). The current cost for 40mg of simvastatin can be as little as 66p/28days; not the £4.87 as used in this analysis. Also, while the price of simvastatin has and will continue to fall, it is important to recognise that the cost of hospital care has risen, and will continue to rise, from the 2001 prices used in this analysis. The event rate in low risk group of the HPS,is similar to that recomended by NICE for treatment with a statin. If we project the cost savings seen in this low risk group (3) taking into account the full actual effect of taking a statin against not taking a statin, and inflation; then over five years each patient treated with simvastatin will have some £900 less in hospital costs, for the cost to the NHS for less than £45 for the simvastatin . The possibility to save £20 for every £1 spent on treatment should leave sufficient to fund a comprehensive risk assessment and monitoring programme. Rarely has a health service had such an opportunity to prevent such serious disease in so many people with such safe and effective treatment, at so little cost. (1)Pulse, pg1 8th October 2005 (2)www.screening.nhs.uk/diabetes/vascular_control.DOC (3)JSAshcroft BMJ 2006;332:1512 (24 June), (4)Lancet 2005; 365: 1779-85 Competing interests: None declared
Competing interests 7 December 2006
Jeffrey R Johnstone, Self-employed Home Send response to journal: Re: Competing interests	The authors of this study say "Competing interests: The Clinical Trial Service Unit, University of Oxford (JA, SP, RC), does not accept honoraria or other payments from the drug industry, except for reimbursement of costs to participate in scientific meetings." But in the same paragraph they say: "The Clinical Trial Service Unit and the Health Economics Research Centre have received research funding through the University of Oxford from Merck & Co and Roche Vitamins Ltd." These statements are contradictory. If research is conducted and reported properly it should matter little how it was funded. But because the BMJ requires a declaration of competing interests, such declaration should make sense. ray@iinet.com.au Competing interests: None declared
Marginal vs average costs 9 December 2006
Adam Jacobs, Director Dianthus Medical Limited, London SW19 3TZ Send response to journal: Re: Marginal vs average costs	If I have understood correctly, the results presented represent the average, not marginal, cost effectiveness of statin treatment in various age groups. The conclusions of the paper are that, because statin treatment is cost effective on average in younger age groups, it would be appropriate to prescribe regular statin treatment to younger patients. However, I am not convinced that this is asking the question in the right way. Suppose you have a 40-year-old patient and want to know whether you should start statin treatment now or wait 10 years before starting. To make that decision (at least from an economic perspective), you need to know the marginal cost effectiveness of regular statin treatment starting at age 40 relative to starting at age 50. Could the Heart Protection Study Collaborative Group enlighten us on whether looking at marginal costs would lead to the same conclusions? Competing interests: My company provides consultancy services to pharmaceutical companies.
Re: Marginal vs average costs 11 December 2006
L S Lewis, GP Surgery, Newport, Pembrokeshire SA42 0TJ Send response to journal: Re: Re: Marginal vs average costs	'In a 40 year-old at 20% CVD risk , would it be best to start treatment now, or wait another ten years ? That's a very interesting question ! I would like to answer it as a clinician. I just did a rough calculation on my desktop Framingham calculator. To just exceed a 20% CVD risk , I generated a 40- year old male with the following profile:- SystolicBP = 145 ; Smoker ; Total Cholesterol = 7.9 ; HDL = 1 ; Non-Diabetic ; No ECG LVH As can be seen - he is NOT an average 40 year old, and should be concerned for his future ! I would give him an Aspirin, Simvastatin, and advise him not to smoke .. If I do not treat him with a Statin, I will be withholding a 30% reduction in his 20% ten-year chance of a CVD event, and a 20% reduction in his risk of death IN THE NEXT TEN YEARS - I will explain to him that treatment is no guarantee of survival, nor benefit. Only three in fifteen men such as he will have an event in the next ten years, and my treatment will prevent just one of those events. I expect most men given such an offer will take the treatment. I also expect most Health Accountants to complain about the costs - but would respond that we are saving both lives AND money here, as the HPS group's paper testifies.. If we merely want to save money we should close down the NHS. What would you do ? The whole question of what to do when he is fifty is predicated on getting him there ! This same profile in a man of 50 calculates at 34% CVD risk. Of even greater concern to me is my younger patient, who tells me of his fearful family history, and asks for a STATIN.. but his calculated risk , even multiplied by 1.5 as recommended, does not tip the 20% NICE threshold. Presently I am at a loss to know the answer - using a calculated risk threshold is clearly favouring the OLDER, the SMOKER, and the MALE. Do not look a gift-horse in the mouth ! Simvastatin is now so cheap it is fast approaching Aspirin status. Dr L S Lewis GP Competing interests: life vs. money
The evidence mounts further yet we are still failing to provide basic care to those who need it most 19 December 2006
Beck Taylor, Specialist Registrar Public Health Heart of Birmingham PCT B16 9PA, Andrew Rouse, Consultant in Public Health Send response to journal: Re: The evidence mounts further yet we are still failing to provide basic care to those who need it most	Editor - This study adds to what should now be common knowledge amongst primary care practitioners, namely that statins are not only clinically effective, but are also cost effective, and at clinical risk levels below current recommendations. Remarkably, however, we have found that even many high-risk patiens are not receiving this simple, life- prolonging treatment. Residents of Heart of Birmingham PCT (HoB) area have one of the lowest life expectancies in the UK, and the gap between our residents and the English population as a whole is not closing. Around 50% of excess deaths in HoB are due to circulatory disease. We recently conducted an audit of all CHD-related deaths in Sparkbrook, one of Birmingham's most deprived wards. We identified all CHD-related deaths occurring between 2003 and 2005 (as per death certificate), and reviewed the electronic primary care notes. We identified 124 deaths having occurred, and were able to collect data on 72 of these individuals (76% of HoB patients). 38% of deaths occurred in patients under the age of 75. The male:female ratio was 2:1, and more than 2/3 were of South Asian origin. 81% of deaths occurred in patients with a known diagnosis of hypertension, CHD, diabetes, hyperlipidaemia, or chronic kidney disease (CKD), many of whom would be eligible for statins under current 10-year risk guidelines. Of these patients, 41% were not prescribed a statin; 50% of CHD sufferers, and 42% of diabetics. It is disheartening to find such low levels of prescribing in patients for whom statin therapy may have been of benefit. Those audited may be the few who have 'slipped through the net' of care, but it is likely that there are many with similar risk profiles who remain untreated in our community. The Quality Outcomes Framework (standards of care set out in the general practitioner contract) provides some hope by providing general practitioners with a financial incentive to reduce their CHD and diabetic patients' cholesterol below 5mmol/l. However, there is no incentive to prescribe statins. In patients with CHD or diabetes who have a cholesterol less than 5, or individuals without these specific diagnoses, there is no incentive at all. Nearly a quarter of patients on our PCT CHD register do not have a cholesterol result below 5, and it is likely that many with a 'normal' cholesterol are not taking a statin. The current National Service Framework for CHD does not advise statins in CHD patients with cholesterol below 5, and more explicit guidance is urgently required from NICE. It is clear that evidence of effectiveness is not enough to ensure that patients receive the appropriate care, as the benefits of statins in at-risk patients with a cholesterol below 5 have been known for over 4 years (1). We suggest that the General Medical Services contract needs to incorporate up-to-date evidence wherever possible, in order to drive down morbidity and premature mortality from CHD. We now know that statins present a cost-effective intervention, even in lower risk groups. We cannot afford to ignore this fact if we are to reduce the impact of heart disease on our population. Statins most certainly don't save lives, but they do delay death. (1) MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,563 high-risk individuals: a randomised placebo- controlled trial. Lancet. 2002 Jul 6;360(9326):7-22. Competing interests: None declared
Re: The evidence mounts further yet we are still failing to provide basic care to those who need it most 20 December 2006
L S Lewis, GP Surgery, Newport, Pembrokeshire SA42 0TJ Send response to journal: Re: Re: The evidence mounts further yet we are still failing to provide basic care to those who need it most	Beck Taylor's audit appears to show that Statins are not reaching the parts of the population that might benefit, and she places the onus firmly on GP incentives for better practice... It is surprising to find a Public Health doctor espousing the medicalisation of ever-larger cohorts in the cause of a drug company, before exploring 'population change'. It might present a better balance to ask what the smoking levels, the exercise quotients, and the Abdominal girths were in those afflicted in the Heart of Birmingham. Turning to the GP's role, it might be further asked how many 'patients' in the at-risk groups were taking the very cost- effective, and long-known Aspirin-a-day ? The GP needs merely recognise the risk, and offer the prescription ! Whereas with Blood-pressure, and chloesterol targets , there is in fact a mountain of work measuring, and re-measuring, adjusting and checking and testing for side-effects etc., just to meet the bizarre and unevidenced Quality and Outcomes Framework cholesterol targets. QOF barely re-imburses the costs of this intensive work which medicalises ever larger portions of the 'normal' population, in regular surgery attendance, when the best evidence suggests that men over 50 years can take 10mg Simvastatin over-the-counter with near equal effect, and without knowledge of their cholesterol. But let us not get too carried away with the idea that Statin is a magic cure - it isn't ! Even if EVERYBODY took it, we could expect at best a 20% reduction in deaths from IHD. It is still has a way to go before it approaches Aspirin as a cheap, easy, and reasonably safe 'fire- and-forget' prevention, available to every adult over-the-counter, with or without prescription. Dr L S Lewis Competing interests: None declared
Agreement between PH and GPs? 21 December 2006
Richard G Richards, Consulatnt in Public Health Nottinghamshire County tPCT, 65 North Gate, Newark, NG24 1HD Send response to journal: Re: Agreement between PH and GPs?	I share Lewis’s analysis of the whole statin issue. Local policy has always been to calculate risk first then seek to change lifestyles to reduce risk, using the calculator to demonstrate on screen to patients the reduction in risk resulting from say stopping smoking. If there are changes to lifestyle then the risk should be recalculated and a statin might not be necessary. We also recommended 40 mg simvastatin for all, though that was before the drug came off patent and when MSD charged the same for 40mg as 10 mg. The rules for Quality and Outcomes Framework messed up our pragmatic policy of ‘take 40mg and you don’t need to come back for more blood tests’: indeed we discussed maintaining our policy and reimbursing any GP who followed our policy but missed out on QOF payments as a result. The National Service Frameworks have been a boon to population health care as they have focused on the ‘80%’ (QOF does not always match the NSFs). However, it’s a characteristic that clinicians, particularly consultants, tend to focus on the (more interesting) ‘outliers’, to the detriment of ensuring care to the many who would benefit. The cost effectiveness of using cheaper 10mg a day would need to take into account repeat cholesterol testing if we are concerned with the 20% who will not respond to 10mg. Lewis does, however, fall into the ‘relative risk reduction’ trap discussed in the current BMJ (16th December 2006, pp 1248-50), by telling patients of a 20% reduction in the risk of death. Relative risk is a meaningless piece of information without absolute risk. Furthermore patients need to have statistical information presented to them in a manner they can relate to everyday life (hence my use of ‘years needed to take’). The risk calculators should not be used on those with a family history. A General Practitioner could either treat the patient with advice, aspirin and a statin (if their risk is high, a reduction in even a ‘normal’ cholesterol will give benefit) or refer to a consultant with an interest; who will give advice, aspirin and a statin. My colleagues in Birmingham should be forgiven for failing to do one of their first duties according to Osler: ‘to educate the masses not to take medicine’. They are faced with dealing with the consequences of the power of commercial interests (over citizens and Governments alike) that turns ordinary folk into ‘profit fodder’ by promoting unhealthy lifestyles and then medication to counter the adverse results. Competing interests: None declared
We must get the basics right 22 December 2006
Beck Taylor, Specialist Registrar Public Health Heart of Birmingham tPCT, B16 9PA Send response to journal: Re: We must get the basics right	I wholeheartedly agree with Lewis and Richards: statins are not a silver bullet in the fight against coronary heart disease. It is vital that patients, and the population as a whole, are also informed, empowered, and encouraged to reduce their coronary heart disease (CHD) risk through lifestyle change. In the earlier rapid response I only alluded to the statin element of our audit. We looked at other treatment and lifestyle factors, but as these were not directly related to the Heart Protection Study paper they were not discussed. For example, in many cases, smoking status was unrecorded, and less than half of smokers had a record of cessation advice being offered. Diet and physical activity advice were rarely recorded in patients with known disease, and 25% of CHD patients were not prescribed aspirin (no contraindication recorded). In Heart of Birmingham tPCT our population has a high baseline risk of CHD as a result of high levels of deprivation, and a large South Asian community. We have one of the highest premature death rates in the UK. Eight out of ten deaths in our audit were in patients known to have CHD- related diagnoses, and there were many missed opportunities for intervention. Patients must have the opportunity to choose whether to use smoking cessation services, or take a statin or antihypertensive, and it is clear that this is not always the case. Of course, we must not forget population-based public health approaches to tackling lifestyle- related diseases. However, we must also get the basics right with high- risk patients, including offering statins to eligible individuals. Competing interests: None declared