Introduction
The National Institute for Health and Care Excellence (NICE) guidelines on preventing cardiovascular disease have recently been updated, with significant changes to recommendations on lipid management.1 The new guidance has featured prominently in the national press because of the extended range of patients who are now potentially eligible for lipid-lowering therapy. This reflects a change in emphasis on lipid management towards considering a patient’s lifetime risk of cardiovascular disease (CVD) and the potential benefits of intervening with treatment at a younger age. The guidance also reflects a change towards treating lipid levels to target as opposed to the previous ‘fire and forget’ approach, which will have significant implications for primary care.
Which patients are now eligible for primary prevention?
NICE continues to recommend using a 10-year CVD risk score, such as QRISK3, to help inform which patients may benefit from primary prevention. According to guidance, those with a 10-year CVD risk score >10% should be offered a statin. However, NICE now suggests that GPs also ‘do not rule out’ treatment for those with a QRISK3 score <10%.1 This new recommendation is supported by a NICE cost-effectiveness analysis that found evidence in favour of statin treatment even down to the youngest modelled age group and QRISK scores of 40 years and 2% respectively.2 However, although there are benefits from statin treatment at a population level, at the individual patient level the absolute risk reduction from statins in people with a QRISK score of 5% is relatively low at 1.9% over 10 years, compared with 7% at the 20% QRISK threshold.3 The higher the QRISK score, the lower the number needed to treat (NNT). NICE estimates that the NNT to prevent a cardiovascular event or stroke with a high-intensity statin for 10 years is 54 at a QRISK threshold of 5%, 25 at a threshold of 10%, and 14 at a threshold of 20%.3 NICE also recommends that statins should be considered for people aged ≥85 years.2
While the change in guidance potentially opens the way to millions more people being eligible for statins, the terminology is important here. This is a weaker recommendation for statins compared with the guidance to offer a statin to those with a QRISK3 >10%. The change in guidance does allow for greater patient choice among those at lower risk. A more individualised decision is needed, which may be informed by using a lifetime risk tool, such as QRISK3-lifetime, particularly among people aged under 40 years with CVD risk factors. A pooled analysis of 400 000 patients reported that the greatest increase in the relative risk of long-term CVD was among those with higher non-high-density lipoprotein (HDL) cholesterol detected before the age of 45 years.4
Despite the media focus on a broader population of people being potentially eligible for statins, it is important to also consider that people with established CVD or those with the highest primary prevention QRISK scores (for example, >20%) still stand to benefit the most from lipid-lowering therapies. However, CVDPREVENT audit data from England report that lipid-lowering therapy is not currently prescribed for approximately 40% of people with a QRISK score >20% as primary prevention, and nearly 20% of people with established CVD (https://www.cvdprevent.nhs.uk/). Locality and practice-level quality improvement projects might be better to focus on increasing appropriate prescribing among these higher-risk cohorts.
Does it matter which CVD risk score?
The guideline supports the use of QRISK3 but recognises that clinicians may need to continue using QRISK2 given QRISK3 is not integrated into most electronic health record systems. QRISK3 includes additional parameters, such as migraine, severe mental illness, and corticosteroid or antipsychotic medication, so QRISK2 may underestimate risk for some patients. QRISK4 has been published since the NICE guideline was released and includes seven new risk factors, including chronic obstructive pulmonary disease, Down’s syndrome, learning disability, and lung, brain, oral, or haematological cancers.5 QRISK scores should not be used for patients with type 1 diabetes, chronic kidney disease, or familial hypercholesterolaemia, and separate guidance covers these conditions. The ASSIGN score is recommended in Scotland.6
Statin intolerance and risks
Statins are the first-line lipid-lowering treatment. Prior to initiating statins, clinicians should perform a baseline assessment to review further opportunities for CVD prevention and determine whether statins are the most suitable treatment. NICE emphasises the importance of discussing statins’ potential negative effects with patients, such as drug interactions and statin side effects. GPs need to be aware of statin reluctance and the nocebo effect: previous crossover trials have shown that, although daily negative symptom scores are higher while taking statins, many patients report similar increased levels of symptoms while taking a placebo.7 Around 90% of muscle symptoms attributed to statins are thought to be due to the nocebo effect.3 Discussing these points in advance of treatment may help to improve adherence. Statin intolerance is often overestimated and most patients with possible side effects should be able to tolerate a lower dose or alternative statin.8
Although statins are associated with a small increased relative risk of adverse effects including diabetes (number needed to harm of 200 over a 5-year period), × three-fold rise in transaminases (occurs in around 1 in 250 people prescribed a statin), and myositis (2–22 cases per 10 000 patient years), for most patients these are outweighed by the reduction in risk of cardiovascular disease.3,9
Treatments and targets
Statins lower low-density lipoprotein (LDL) cholesterol levels by around 30% on average, with a corresponding 21% reduction in risk of major vascular events per 1.0 mmol/L reduction in LDL when used for primary prevention.10 Atorvastatin is recommended as the initial lipid-lowering treatment because it is high intensity and cost-effective. The initial primary and secondary prevention doses remain as 20 mg and 80 mg respectively. A reduced starting dose may be considered if this is the patient preference, or if there is felt to be a high risk of side effects based on previous medication reactions or potential drug interactions.
Repeat lipid levels should be checked within 3 months of starting therapy. For primary prevention, the aim is for >40% reduction in non-HDL cholesterol (Figure 1). For secondary prevention, the target is an LDL ≤2.0 mmol/L, or non-HDL ≤2.6 mmol/L (Figure 2), and this secondary care target is directly reflected in the Quality and Outcomes Framework (QOF), indicator CHOL004, with an additional QOF indicator (CHOL003) pertaining to practices maintaining a record of secondary prevention patients. Clinicians working with patients should ideally aim to increase the statin dose or intensity if these targets are not met, but the NICE guideline encourages patient-centred care and individualised treatment. European guidelines recommend an LDL target below 1.4 mmol/L in very high-risk patients, so such targets may be suitable for some patients.11 NICE considered a secondary prevention LDL target <1.8 mmol/L but decided against this, recognising the significant impact a lower target would have on primary care workload and concerns around cost-effectiveness. For others, it may be a case of accepting a more modest reduction in non-HDL if patients are opposed to treatment intensification. NICE has produced a patient decision aid to help make statin treatment an informed choice.12
Figure 1. Flowchart summarising the NICE-recommended approach to primary prevention treatment of cardiovascular disease. CVD = cardiovascular disease. eGFR = estimated glomerular filtration rate. HDL = high-density lipoprotein. HIV = human immunodeficiency virus. LDL = low-density lipoprotein. NICE = National Institute for Health and Care Excellence.
Figure 2. Flow chart summarising the NICE-recommended approach to secondary prevention treatment of cardiovascular disease. HDL = high-density lipoprotein. LDL = low-density lipoprotein. NICE = National Institute for Health and Care Excellence.
If a maximum-dose statin is insufficient, once-daily ezetimibe can be considered as an additional agent, with the IMPROVE-IT study demonstrating a reduction in cardiovascular events with this approach in a secondary prevention population.13 Bempedoic acid can be indicated for patients who are intolerant of statins in combination with ezetimibe, and both drugs can be initiated in primary care. Patients where none of these options are suitable or where these prove ineffective should be considered for newer intensive lipid-lowering drugs such as PCSK9 inhibitors or inclisiran, which may need to be initiated following discussion with, or referral to, specialist care. NICE has approved the use of inclisiran but trial outcome data are awaited, pending the conclusion of the ORION-4 study, likely to be in late 2025. NICE recommends avoiding prescribing fibrates for CVD prevention. However, in the secondary prevention setting, patients prescribed a statin who have an LDL >1.04 mmol/L and ≥2.6 mmol/L and a fasting triglyceride >1.7 mmol/L can be considered for icosapent ethyl, though specialist recommendation may be required before this is initiated in some areas.
This move towards treatment targets for both primary and secondary prevention represents a substantial shift in the approach to lipid-lowering therapy and a move away from a ‘one size fits all’ approach.
NICE offers updated information about lifestyle interventions for prevention of CVD, including recommending a cardioprotective diet, increasing physical exercise, maintaining a healthy weight, reducing alcohol intake, and stopping smoking. For primary prevention, these may be offered prior to statins, but, for secondary prevention, they should be offered at the same time.
What does this mean for GP workload?
The move towards targeted lipid treatment with a greater range of therapies for a broader population of people may come with significant workload implications for primary care, but it is hoped that optimising treatments may lead to fewer future cardiovascular events. Prevention of CVD represents a cornerstone of primary care work and offers an opportunity to reduce health inequalities and improve population health.
For primary prevention, NICE continues to recommend that clinicians use QRISK to estimate an individual’s risk of a cardiovascular event over the next 10 years and prioritise treatment among those with the highest scores. However, QRISK scores should be seen as representing a continuum of risk and NICE suggests that clinicians ‘do not rule out’ intervention for people with a QRISK score <10%, allowing for more patient choice and recognising the importance of lifetime risk in younger patients. Lifestyle interventions may be considered as an initial lipid-lowering intervention, while statins remain the first-line medication. Treatment should be titrated up to achieve at least a 40% reduction in non-HDL for primary prevention or a non-HDL of 2.0 mmol/L or below for secondary prevention. This may require the addition of ezetimibe or other additional treatment agents beyond statins, even in a primary prevention scenario.
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Notes
Funding
Nicholas R Jones is funded by the NIHR.
Provenance
Freely submitted; externally peer reviewed.
Competing interests
Thomas Round is an Associate Editor for the BJGP and Clinical Lead for Royal College of General Practitioners (RCGP) Essential Knowledge Updates (EKU) e-learning. Nicholas R Jones is a writer for RCGP EKU e-learning and wrote the EKU 2024.1 module ‘Cardiovascular disease: risk assessment, reduction & lipid modification’.
- © British Journal of General Practice 2024
References
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(2017) Scottish Intercollegiate Guidelines Network. Risk estimation and the prevention of cardiovascular disease. SIGN 149 (SIGN, Edinburgh)
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