- Cardiovascular disease remains a major cause of morbidity and is responsible for a third of all deaths in the UK
- The new clinical guideline for lipid modification (NICE CG181) increases the number of people eligible for statin treatment in England by 4.5 million
- The change in threshold for offering primary prevention to those with a greater than 10% 10-year risk of cardiovascular events is justified by clear evidence of benefit, very small risk of harm, and the recent considerable reduction in the cost of statins
- Atorvastatin 20 mg daily, a ‘high intensity’ dose, should be offered as the initial intervention for primary prevention as it will achieve a 40% reduction in non-HDL cholesterol in most people; this reduction conveys greatest benefit
- Patients should be offered an annual medication review, and measuring non-fasting lipid levels may help in informing and supporting this process
- Non-HDL cholesterol can be measured without the need for fasting lipids and provides a good indicator of treatment effect:
- laboratories will need to change their reports and clinicians will need to get used to the new values
- Atorvastatin 80 mg daily should be used in all people with established CVD:
- a lower dose or alternative statin should be used if this dose is not tolerated
- Perhaps the biggest challenge will be the need, in offering statins to people for primary prevention, to explore their beliefs and values, communicate risk and benefit, and help them reach a decision on intervention.
In 2014, NICE issued Clinical Guideline (CG) 181 on Lipid modification—cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease (available at: www.nice.org.uk/guidance/cg181).1 NICE CG181 is an update of the 2008 NICE guideline on lipid modification (CG67) and Technology Appraisal (TA) 94 on statins, and also updates and incorporates other guidance on lipid treatment from NICE guidelines including: diabetes (CG15 and CG66/87,)2,3 and chronic kidney disease (CG73, now CG182).4,5 It is fair to say that the lipid modification and cardiovascular risk assessment recommendations have been controversial: various commentators have criticised the guideline over the lower thresholds and large increase in the number of people now eligible for statins, and raised the spectre of over-medicalisation6 and ‘mass statinisation’.7 Perhaps surprisingly, some of the press coverage has been positive and recognises the scale of benefit that could be achieved if the guidelines are implemented.8
Cardiovascular disease is a major threat to health
One reason for wishing to prevent or delay CVD and death in a large proportion of the population is that over one half of us will have a heart attack or stroke in our lifetime and a third of us will die from this. Cardiovascular disease is the leading cause of death in England and Wales and in 2010, 180,000 people died from CVD;1 around 80,000 of these deaths were caused by coronary heart disease and 49,000 by strokes, and 70% of the deaths were in men. Cardiovascular disease death rates peaked in the 1970s and 1980s, but have more than halved since that time; it is interesting to note that rates have fallen more rapidly in older age groups compared with younger ones, with an approximately 50% reduction in the 55–64 year age group compared with a 20% reduction in men aged 35–44 years.1 Cardiovascular disease is also more common where there is social deprivation and also in people in the UK of South Asian origin.11 As obesity levels rise and associated type 2 diabetes becomes more prevalent, there is a clear need to maximise preventative interventions in as many people as possible who are at risk.
Benefits and scale of treatment
NICE has estimated that if the recommendations in CG181 on primary prevention are implemented (i.e. offering treatment to people with a greater than 10% 10-year cardiovascular risk), up to 8000 lives could be saved every 3 years. The impact on CVD events is also significant and this change could prevent up to 28,000 heart attacks and 16,000 strokes each year. To achieve this, it is estimated that in England, 4.5 million extra people will now be offered a statin.5 At the previous 20% level of risk recommended in the NICE 2008 guideline, 13 million people were eligible for treatment, but only around 7 million of these individuals are currently receiving prescriptions.6 It is estimated that these increases in prescribing as a result of updated recommendations in NICE CG181 will raise overall drug costs by more than £52 million a year (the overall drug budget is over £10 billion). To put this figure into context, in 2005 atorvastatin cost the NHS in England £400 million. In 2013, this figure was less than £50 million because of the much cheaper cost of generic atorvastatin. For simvastatin, the cost was £100 million in 2005 and just over £50 million in 2013.12
Priorities for implementation
See Box 1 below for the recommendations identified in NICE CG181 as key priorities for implementation.1
Box 1: NICE Clinical Guideline 181—key priorities for implementation1
Identifying and assessing cardiovascular disease risk
- For the primary prevention of CVD in primary care, use a systematic strategy to identify people who are likely to be at high risk
- Prioritise people for a full formal risk assessment if their estimated 10-year risk of CVD is 10% or more
- Use the QRISK2®13 risk assessment tool to assess CVD risk for the primary prevention of CVD in people up to and including age 84 years
- Do not use a risk assessment tool to assess CVD risk in people with an eGFR less than 60 ml/min/1.73 m2 and/or albuminuria;a these people are at increased risk of CVD. (NB: See recommendation 1.3.27 for advice on treatment with statins for people with chronic kidney disease.)
Lipid modification therapy for the primary and secondary prevention of CVD
- Before starting lipid modification therapy for the primary prevention of CVD, take at least one lipid sample to measure a full lipid profile. This should include measurement of total cholesterol, HDL cholesterol, non-HDL cholesterol, and triglyceride concentrations. A fasting sample is not needed
- Offer atorvastatin 20 mg for the primary prevention of CVD to people who have a 10% or greater 10-year risk of developing CVD.* Estimate the level of risk using the QRISK2 assessment tool
- Start statin treatment in people with CVD with atorvastatin 80 mg.b Use a lower dose of atorvastatin if any of the following apply:
- potential drug interactions
- high risk of adverse effects
- patient preference
- Measure total cholesterol, HDL cholesterol, and non-HDL cholesterol in all people who have been started on high intensity statin treatment at 3 months of treatment and aim for a greater than 40% reduction in non-HDL cholesterol. If a greater than 40% reduction in non-HDL cholesterol is not achieved:
- discuss adherence and timing of dose
- optimise adherence to diet and lifestyle measures
- consider increasing dose if started on less than atorvastatin 80 mg and the person is judged to be at higher risk because of comorbidities, risk score, or using clinical judgement.
[This recommendation updates and replaces recommendation 220.127.116.11 from Type 1 diabetes (NICE CG15)].2
aPeople on renal replacement therapy are outside the scope of this guideline.
b At the time of publication of NICE CG181 (July 2014), atorvastatin did not have a UK marketing authorisation for this indication. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council’s Good practice in prescribing and managing medicines and devices14 for further information.
*includes those with type 2 diabetes
CVD=cardiovascular disease; eGFR=estimated glomerular filtration rate; HDL=high-density lipoprotein; CG=clinical guideline
Adapted from: NICE (2014). Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. Clinical Guideline 181. Available at: www.nice.org.uk/guidance/cg181 Reproduced with permission.
What are the big changes in clinical practice?
Risk assessment for primary prevention, including in people with type 2 diabetes, using QRISK2®
Reducing the threshold to 10%
Initially offering atorvastatin 20 mg daily for primary prevention
|Reduction in low-density lipoprotein cholesterol|
|1 20%–30%: low intensity.
2 31%–40%: medium intensity.
3 Above 40%: high intensity.
4 Advice from the MHRA: there is an increased risk of myopathy associated with high-dose (80 mg) simvastatin. The 80 mg dose should be considered only in patients with severe hypercholesterolaemia and high risk of cardiovascular complications who have not achieved their treatment goals on lower doses, when the benefits are expected to outweigh the potential risks.
*The information used to make the table is from Law M, Wald N, Rudnicka A. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta analysis. BMJ 2003; 326: 1423.
|NICE (2014). Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. Clinical Guideline 181. Available at: www.nice.org.uk/guidance/cg181 Reproduced with permission.
When to consider increasing atorvastatin dose up to 80 mg daily
Give atorvastatin 80 mg daily to all people with a history of CVD
No need for fasting samples; use non-HDL cholesterol as a measure of treatment effect
No routine need for other lipid-modifying drugs
The toughest challenge?
- NICE CG181 has major workload implications for primary care as it significantly increases the number of people recommended to take statins and also requires annual review of all these patients, with blood tests and a face-to-face consultation:
- the added workload is likely to be far more of a barrier to implementation that the cost of the statins, which are now generic and of low cost
- As yet, there is no recognition of the extra work for primary care in budget allocations, or any incentives in the QOF for 2015/2016
- clinical commissioning groups will therefore need to discuss carefully with NHS England how the resources and incentives can be found to support primary care in implementing this guidance
- Clinical commissioning groups should also discuss with local public health departments as to how NHS Health Checks and assessments of CVD risk can be targeted to those most at risk, as recommended in this guidance.
- NICE. Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. Clinical Guideline 181. NICE, 2014. Available at: www.nice.org.uk/guidance/cg181
- NICE. Type 1 diabetes: Diagnosis and management of type 1 diabetes in children, young people and adults. Clinical Guideline 15. NICE, 2014. Available at: www.nice.org.uk/guidance/cg15
- NICE. Type 2 diabetes: The management of type 2 diabetes. Clinical Guideline 87. NICE, 2009. Available at: www.nice.org.uk/guidance/cg87
- NICE. Chronic kidney disease: early identification and management of chronic kidney disease in adults in primary and secondary care. Clinical Guideline 182. NICE, 2014. Available at: www.nice.org.uk/guidance/cg182
- NICE website. News and features. Wider use of statins could cut deaths from heart disease. 18 July 2014. Available at: www.nice.org.uk/News/Article/wider-use-of-statins-could-cut-deaths-from-heart-disease (accessed 22 August 2014).
- BBC News. 18 July 2014. Statins: Millions more to get drugs in controversial plans. Available at: www.bbc.co.uk/news/health-28352290 (accessed 28 September 2014).
- Wise J. Open letter raises concerns about NICE guidance on statins. BMJ 2014; 348: g3937.
- The Independent. 18 July 2014. From: Prescribing statins more widely ‘could avert tragedy’, new medical guidelines suggest. Available at: www.independent.co.uk/news/science/prescribing-statins-more-widely-could-avert-tragedy-new-medical-guidelines-suggest-9613424.html (accessed 28 September 2014).
- Finegold J, Manisty C, Goldacre B et al. What proportion of symptomatic side effects in patients taking statins are genuinely caused by the drug? Systematic review of randomized placebo-controlled trials to aid individual patient choice. Eur J Preventive Cardiol 2014; 21 (4): 464–474.
- Macedo A, Taylor F, Casas J et al. Unintended effects of statins from observational studies in the general population: systematic review and meta-analysis. BMC Medicine 2014; 12: 51.
- Bhopal R. Epidemic of cardiovascular disease in South Asians. BMJ 2002; 324: 625–626.
- Health and Social Care Information Centre. Prescriptions dispensed in the community, statistics for England: 2003–2013. Available at: www.hscic.gov.uk/searchcatalogue?productid=14988&topics=0%2fPrescribing&sort=Most+recent&size=10&page=1#top (accessed 28 September 2014).
- University of Nottingham and EMIS. QRISK2-2014 risk calculator website. www.qrisk.org (accessed 26 August 2014).
- General Medical Council. Good practice in prescribing and managing medicines and devices. Prescribing guidance: Prescribing unlicensed medicines. London: GMC, 2013. Available at: www.gmc-uk.org/guidance/ethical_guidance/14327.asp (accessed 26 August 2014).
- NICE. CG181 Lipid modification: costing report. Available at: www.nice.org.uk/Guidance/CG181/Costing (accessed 27 September 2014).
- Ebrahim S, Taylor F, Brindle P. Statins for the primary prevention of cardiovascular disease. BMJ 2014; 348: g280.
- Di Angelantonio E, Sarwar N, Perry P et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA 2009; 302 (18): 1993–2000.
- NICE. Ezetimibe for the treatment of primary (heterozygous-familial and non-familial)hypercholesterolaemia. NICE Technology Appraisal 132. NICE, 2007. Available at: www.nice.org.uk/guidance/TA132