Statins, CVD prevention and the practice nurse

Changes to NICE’s guidance on lipid lowering mean that many more patients are likely to be eligible for a statin. But what does it mean in practice?

Sometimes you can’t help thinking that working for the National Institute for Health and Care Excellence (NICE) is a bit of a poisoned chalice. Charged with making authoritative recommendations about how the NHS conducts its healthcare, it also has a requirement to seek best use of NHS resources. If a treatment costs too much then it is not recommended. At present NICE uses a financial threshold per Quality Adjusted Life Year (QALY) of £20,000 to £30,000.¹

So what do you do when treatment costs fall? For a long time it has been known that lipid levels are linearly related to cardiovascular disease (CVD) risk,² so that there is no obvious threshold above which treatment is a good idea and below which treatment is a bad idea. In the case of statins, the cost of medication has come down substantially in recent years as various drugs have come off patent. This makes a significant difference to the financial situation – the NHS cost of Lipitor 20mg (the original branded form of atorvastatin) is £24.64 a month; the cost of generic atorvastatin 20mg is £1.62.³ So in one sense it is perfectly reasonable that in 2008 NICE recommended treating people with a CVD risk over 10 years of 20%, and then in 2014 changed its recommendation to 10%.

This has also revitalised the ongoing debate about treating risk. Traditionally people have sought help from a doctor, nurse, or other health practitioner when they wanted something fixed – they wanted a symptom to go away. Now we are being encouraged to treat patients not on the basis of what they have, but on the basis of what they might have in some unspecified future. For the example in question, the makers of statins and cholesterol-lowering margarines have a clear vested interest in supporting this trend.

So when NICE updated its recommendations on Lipid Modification last year,⁴ the topic generated a lot of muttering from newspaper columnists, healthcare professionals, taxpayers and patients. What are the facts? And how are practice nurses and general practice going to be involved?

SECONDARY PREVENTION

Case 1

Eric is 75 and has been seeing you in your practice cardiovascular clinic since his heart attack 5 years ago. He has been taking a statin since then, but has had increasing pain from his knees. He has been told it is arthritis, and takes paracetamol regularly, but his pain is not fully controlled. He recently read in his newspaper that statins can cause aches and pains, and is now wondering if he should carry on with them.

Secondary prevention means trying to reduce the risk that someone who has had a CVD episode (heart attack, stroke) will have another one. Pre-existing CVD is a powerful predictor of future CVD events, and the case for reducing cholesterol in these patients is very strong. Patients who have had a CVD event should be on a statin. The Scandinavian Simvastatin Survival Study (4S) is now 20 years old.⁵ It included 4444 patients with coronary heart disease who were treated with simvastatin and followed up for 5.5 years. There was:

• A 33% reduction in coronary events
• A 30% reduction in total deaths

Looked at another way, the Number Needed to Treat (NNT) over 5 years using simvastatin in patients with coronary heart disease is 11 per coronary event, and 27 per coronary death. These are important benefits and well worth having.

The latest NICE guidance supports this view, but now recommends the use of a high dose (80mg) of atorvastatin.⁴

Our patient, Eric, is concerned lest his aches and pains are brought on by his statin treatment. Muscle and joint aches and pains are very common in gentlemen of a certain age, and osteoarthritis is a common cause. Similarly it is not usually possible to abolish the pain completely with analgesia. But what if it is the statin? There is a lack of evidence about the risk of side effects from statins.⁶ A very severe and potentially fatal reaction – rhabdomyolysis – is very rare, of the order of 1 per 100,000 treatment years, but lesser degrees of muscle ache are much more common, quoted at 5% to 10%.⁷ (My patients would say it is more common than this).

The only way to find out is to stop the statin for a month and see if the symptoms go away. If they don’t go away, a different reason for the pain must be sought. If the symptoms do go away, then try the statin again to confirm that it is indeed the statin that is causing the mischief. If the statin is to blame, then the options are: change the dose; change the statin; or just stop statins. It is reasonable to try three different statins before concluding that all statins are implicated.⁴ Stopping statins is an authentic option: the benefits of a statin are worth having, but probably not worth being miserable for. However your patient will also have a view on this.

PRIMARY PREVENTION

Case 2

Sharon is a 43 year old shop worker. Her friend Tracey recently had a heart attack at the age of 55, and since then Sharon has been having some stabbing pains in her chest. She has been checked out by one of the doctors and had a few tests, and it seems clear that she does not have heart trouble herself. However she is now worried about the future. She has a QRISK2 score of 12%, so she has been sent to your clinic for some lifestyle advice and a discussion about whether she should be taking a statin.

Primary prevention means reducing the risk of a CVD event in someone who has never had one before. QRISK2 is currently the recommended risk-assessment test for CVD.⁴ It is based on information collected between 1993 and 2010 and includes data on over 10 million patients registered with 550 general practices in the UK. It is updated annually. The algorithm includes the information in Box 1.

An initial guess about risk can be made just using the data already in the practice records. If there are gaps in the data, then QRISK2 will fill the gaps with a population average. If it looks as though the risk is higher than desirable, then it is a good idea to go through the other items on the list and fully personalise the result. Your practice software will contain a full QRISK2 template, so fill as much of it in with data as you can. If some bits are of data missing, then don’t worry, but the more boxes that are filled then the more accurate is the result.

QRISK2 is a calculation of the CVD risk for the next 10 years. Age is an important CVD risk factor, so younger people, however bad their other risk factors, may well not give a high score. Another option is to look at the lifetime risk of CVD, advocated by the Joint British Societies in its most recent guidance.⁹ JBS3 suggests that as the lifetime risk will always be higher than the 10 year risk (unless you are very old), then informing patients of their higher risk will motivate them to change their unhealthy habits. Or, put another way; frighten the patients to death to make them do what you want. No evidence is presented to suggest that people are motivated by this approach to change their behaviours, but the argument is plausible.

Risk management in CVD is not just about the use of statin drugs, and NICE make extensive recommendations about other ways to reduce risk.

Eating. Not more than 30% of energy from fats and not more than 7% from unsaturated fats. Cholesterol less than 300mg a day. Patients are referred to the NHS Choices Healthy Eating material.¹⁰

Exercise. Each week, 150 minutes of moderate exercise or 75 minutes of intensive exercise, again following NHS Choices advice.¹¹

Weight. Generally try to achieve an ideal weight. This can be helped with reference to the previous NHS Choices material.

Smoking. Don’t.

Alcohol. Stick to the current recommendations for daily and weekly consumption. NHS Choices can help with this as well.¹²

Plant stanols and sterols. Despite the adverts on afternoon television, these are not recommended in any situation.⁴

Statins in primary prevention

The recently published NICE guidance on lipid modification contains many changes from the previous 2008 version. Indeed if you look at the Recommendations section you will see the changes are clearly set out.⁴ The recommendation change that has caught the headlines is the one suggesting a QRISK2 treatment threshold shift from 20% to 10%. This would much more than double the potential ‘market’ for statins in the UK. It is estimated that statins would be recommended for 25% of the population between age 30 and 85,6 and a significantly greater percentage in those aged towards the upper end of this range. These are very big numbers of people.

For primary prevention the recommended dose of atorvastatin is 20mg a day. In the past, simvastatin was the statin of choice, and the evidence of the 4S trial reinforced this selection. Atorvastatin has long been known to be a more powerful way of lowering blood lipids, but now that its cost is comparable with simvastatin, it has become the drug of choice. It also has a longer half life than simvastatin. Statins reduce the release of lipids from the liver into the blood, and this occurs mainly at night. With its shorter half life simvastatin works best if taken at night whereas atorvastatin can be taken at any time of day.

Unfortunately it is not at all clear that taking a statin for primary prevention will do people any good. Even should you choose to trawl through the 302 pages of the full NICE guidance, it is difficult to find any answers to this rather crucial question.⁶ Almost certainly, people who take a statin are less likely to have a heart attack or die of CVD, and this is a good thing. However the jury is still out on whether the use of statins in primary prevention reduces the overall chance of death in people who take them: the evidence is conflicting.¹³ This begs the question: if people who take a statin are less likely to die of CVD, then what are they more likely to die of? One explanation may be the slight increase in the prevalence of diabetes that statins appear to cause.¹⁴ Also, many years ago – before statins were invented – it was suggested that people who tried to reduce their cholesterol were more likely to die in accidents, as if the reduction in blood fats had an effect on the fat composition of the brain: this suggestion was never, to my knowledge, verified.

What is a patient to think? How much benefit is our patient, Sharon, likely to gain from taking a statin? Once started she will be taking the tablets for many years as they only lower cholesterol for as long as they are taken. That’s a lot of tablets, and a lot of prescription costs – taking a statin does not of itself allow for relief from prescription charges and with the cost increasing to £8.20 this month (if you live in England – in Scotland and Wales everyone gets their prescriptions free) and a month’s atorvastatin costing £1.62 (at the time of writing) that’s a healthy profit for the government. Fortunately decision aids exist to assist this decision, but if anything they serve to indicate just how little benefit people at a 10 year risk of 10% are likely to get from taking a statin. At the 10% risk level, 100 people would have to take a statin for 10 years for three of them to be saved from a CVD event: seven will have a CVD event despite taking the statin, and 90 would not have had a CVD event anyway.¹⁵ Unfortunately it is not possible to determine which group your individual Sharon would fall into.

It may be that Sharon wants to take any available opportunity to stop herself ending up like her friend Tracey. Even though she is aware that she might be taking tablets for decades and not get any benefit, she wants to go ahead. She must also be persuaded that the other prevention strategies detailed above are just as, if not more, important than taking a statin. We as health professionals and she as a potential recipient must not be deluded by all the hype that taking a statin is the full, complete, and permanent answer to cardiovascular disease. Prescribing a statin is easy: getting someone to change their lifestyle is not. Even in the throes of a busy general practice life we must be careful not to always opt for the easy strategy.

NICE recommends some preliminaries before starting a statin. Information is useful on:

• Smoking status (an independent risk factor for CVD)
• Alcohol consumption (an independent risk factor for CVD)
• Blood pressure (an independent risk factor for CVD)
• Body mass index or other measure of obesity (an independent risk factor for CVD)
• Total cholesterol, non HDL cholesterol, HDL cholesterol and triglycerides (in primary prevention the TC/HDL ratio is important)
• HbA1c (diabetes is an independent risk factor for CVD)
• Renal function and eGFR (CKD is an independent risk factor for CVD)
• Liver function tests: transaminase level (alanine aminotransferase or aspartate aminotransferase) to be done before starting a statin and then at 3 months and 12 months. As statins work through the liver, stop or do not start the statin if transaminase levels are above 3 times the local laboratory maximum
• Thyroid stimulating hormone. Thyroid underactivity raises lipid levels.

CONCLUSION

Cardiovascular disease has become a major area for prevention with the development of risk-assessment tools (such as the recommended QRISK2) and lots of different and effective lipid-lowering medications. Indeed, from a prevention point of view, CVD has attracted more attention (and created more work) than almost any other area of health prevention. The NICE guidance has re-activated some old arguments, but in truth NICE is simply applying established economic parameters to an evolving financial situation. At present the evidence suggests that everyone would benefit from taking a statin, it’s just that people who a are already at low CVD risk get only a tiny and arguably negligible benefit.

The idea of preventive care does not always sit comfortably with the traditional patient/nurse relationship, and it is not clear that the established ‘rules’ of such interactions still apply. What are the ethics of treating something that has not happened and which in all probability will never happen? Are ‘patients’ being created un-necessarily? Is the evidence base sufficiently robust to justify such shifts in emphasis? Are we all being seduced into chasing tests and numbers and losing sight of the bigger picture? And what is the impact of the various vested interests – especially the makers of statins – in promoting such developments? These are questions that at present are incompletely answered.

REFERENCES

1. Office of Health Economics. Critique of Research Proposing to Lower NICE’s Cost-per-QALY Threshold to £12,936. December 2013 https://www.ohe.org/news/critique-research-proposing-lower-nice’s-cost-qaly-threshold-£12936

2. Betteridge DJ, Dodson PM, Durrington PN, et al for the British Hyperlipidaemia Association. Management of hyperlipidaemia: Guidelines of the British Hyperlipidaemia Association. Postgraduate Medical Journal 1993;69:359-69.

3. NHS Electronic Drug Tariff (accessed March 2015). http://www.ppa.org.uk/edt/March_2015/mindex.htm

4. NICE CG 181. Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease https://www.nice.org.uk/guidance/CG181

5. Scandinavian Simvastatin Survival Study group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Trial (4S). Lancet 1994;344:1383-9.

6. Goldacre B. Mass treatment with statins. BMJ 2014;348:g4745

7. Patient.co.uk Lipid-regulating Drugs (including Statins). http://www.patient.co.uk/doctor/lipid-regulating-drugs-including-statins

8. Heart UK. Qrisk2. http://heartuk.org.uk/healthcare-professionals/resources-and-publications/risk-calculators/qrisk2

9. Joint British Societies’ consensus recommendations for the prevention of cardiovascular disease (JBS3) Heart 2014;100:ii1-ii67 doi:10.1136/heartjnl-2014-305693

10. NHS choices. Healthy Eating http://www.nhs.uk/Livewell/healthy-eating/Pages/Healthyeating.aspx

11. NHS choices. Health and fitness, exercise. http://www.nhs.uk/livewell/fitness/Pages/Fitnesshome.aspx

12. NHS choices. Drinking and alcohol. http://www.nhs.uk/LiveWell/Alcohol/Pages/Alcoholhome.aspx

13. Ray KK et al. Statins and all-cause mortality in high-risk primary prevention: a meta-analysis of 11 randomized controlled trials involving 65,229 participants. Arch Intern Med. 2010 Jun 28;170(12):1024-31. doi: 10.1001/archinternmed.2010.182.

14. Shah R, Goldfine A. Statins and Risk of New-Onset Diabetes Mellitus Circulation. 2012; 126: e282-e284

15. National Prescribing Centre. Statins patient decision aid. http://www.npc.nhs.uk/therapeutics/cardio/cd_lipids/resources/pda_Lipids.pd