Real-World Challenges: Implementation of NICE Guidance on Statins

Dr Christopher Clark and Dr Joseph Mills Discuss How Implementation and Potential Barriers to the Uptake of NICE Guidance on Preventing CVD Were Considered in a Recent Update

In this new series of articles produced in collaboration with colleagues at NICE, Guidelines in Practice consults key members of a Guideline Development Committee (GDC) to: 

• discuss recommendations in new or updated guidance that may be challenging to implement
• understand how barriers to implementation are taken into account during guideline development
• advise primary care teams on how to overcome these barriers to maximise guidance uptake.

This article focuses on the work of NICE and the guideline’s GDC on identifying and overcoming barriers to the uptake of recommendations around the use of statins in the recently updated Clinical Guideline (CG) 181—Cardiovascular disease: risk assessment and reduction, including lipid modification.¹ This article—based on interviews with Dr Christopher Clark, GP and GDC member, and Dr Joseph Mills, Consultant Cardiologist and GDC Chair—will discuss the challenges to uptake identified during the development of CG181, the reasons underlying these barriers, and the ways in which the updated guideline was adapted as a result. The article will also provide practical advice to maximise the uptake of the guideline in primary care.

The key recommendations discussed in this article are provided in Box 1.

Dr Christopher Clark—The Burden of High Cholesterol and the Need for the Guidance

What Is the Prevalence of Raised Cholesterol in the UK, and Why Is This Significant?

Cardiovascular disease (CVD) is one of the leading causes of mortality worldwide;² in March 2023, ischaemic heart disease was the second biggest cause of death in England and Wales.³ Reducing the risk of CVD is therefore important, and raised cholesterol—although just one of a number of risk factors that feed into a global assessment of cardiovascular risk—is an important element, particularly because it is so amenable to treatment.

We know that most people have a raised cholesterol level when compared with that recommended in CG181.¹ The latest Health Survey for England estimated that, in 2021, the prevalence of elevated cholesterol was 56% among men and 61% among women, a significant increase on previous years.⁴ The treatment of raised cholesterol has moved away from defining a safe cholesterol level to looking at patients and cardiovascular risk more holistically.¹ Nevertheless, treatment of raised cholesterol is key for CVD prevention, and—in contrast to other risk factors for CVD, such as hypertension—patients may be less aware of what a high test result looks like and its potential impact on their health.

What Are the Consequences of Undertreatment of Raised Cholesterol?

It is established that attendance to the NHS Health Check programme is suboptimal—the service consistently provides health checks for fewer than 50% of people who are eligible.⁵ More women than men attend health checks, and people who do respond are often those from less deprived socioeconomic groups.⁶ Unfortunately, risk factors for CVD are more prevalent in the most deprived individuals in society,⁷ explaining why lipid modification is a particular focus of Core20PLUS5—NHS England’s initiative to reduce health inequalities.⁸

Although it is impossible to look back at our patients after 10 years and identify those we prevented from having a stroke, developing angina, or needing a bypass, there is compelling evidence that optimal treatment of raised cholesterol is a positive investment, both at the individual level and at the societal and service levels.⁹ 

At the individual level, we are talking about reducing the chances of a life-changing cardiovascular event. Blood vessel disease does not just happen in one place—it can strike multiple areas of the body, meaning that anyone who is at risk of a stroke is also at risk of heart disease or peripheral arterial disease (PAD). Therefore, undertreating raised cholesterol increases the chances of morbidity or death. 

At the societal and service levels, without risk prevention, the financial burden and workload associated with CVD will continue to rise. In 2019, CVD-related healthcare costs in England were estimated at £7.4 billion per year, with an annual cost to the wider economy of £15.8 billion.¹⁰

What Is Best Practice in the Treatment of Raised Cholesterol?

Primary Prevention

For primary prevention—of patients with cardiovascular risk but without established CVD—best practice relies on measuring someone’s cholesterol as part of holistic healthcare assessment of cardiovascular risk.^1,11 If we can get past the barrier of identification and assessment, then best practice centres on addressing a person’s modifiable risk factors. We would look at a person’s diet and alcohol consumption.¹ We would also exclude any potential secondary causes of raised cholesterol¹—for example, we would think about testing thyroid function, especially in an older woman. However, before we start to modify these risk factors, it is important to identify them all, considering the person as a whole.¹ Once this cluster of risk factors has been identified, it is best practice to have a discussion about cardiovascular risk with the patient, based on their cholesterol level and blood pressure, and taking into account demographic factors, family history, and medical history.¹ 

Regardless of the assessments that are undertaken, patients will follow a common pathway of interventions to address cardiovascular risk. We know that we can make some difference to cholesterol level by optimising diet, body mass index, and exercise levels, and CG181 stresses the importance of making lifestyle change before statins are started.^1,12,13 However, although these lifestyle interventions have benefits that extend beyond cholesterol and cardiovascular health and should be encouraged, we also know that their impact on cholesterol is likely to be smaller than that of a statin, and that the impact of specific dietary interventions on cardiovascular and all-cause mortality remains unclear.^14–17 

In my experience, to lower cholesterol levels to an extent that will improve cardiovascular risk and lower mortality, pharmacological therapy is generally required. Therefore, although it is important to support patients through a period of lifestyle modification, they may feel demoralised if they find that their changes have not made a sufficient impact, and may be tempted to give in or stop attending follow-up appointments. However, this presents an opportunity for the clinician to show their patient that there is a valid reason for intervening with a drug, and may even promote adherence to it.

Once pharmacological intervention has been decided upon, it is best practice to avoid initiating this in isolation—patients may also require treatment to lower their blood pressure, for example. When discussing drug treatment for raised cholesterol, we are almost always talking about prescribing a statin. Although a range of statins is available for primary prevention, the updated guideline has been simplified to recommend a standard, single dose of a generic statin (atorvastatin) with a low acquisition cost and an acceptable side-effect profile (see In Light of These Barriers, How Was CG181 Adapted to Enhance Its Implementability?).^1,17,18 

This broad recommendation of a single drug and dose may feel at odds with a patient-centred approach, but it minimises the need for a protracted period of testing and adjustment, which can compromise adherence to treatment¹⁸—especially if a patient perceives that they will need to take a higher dose of a drug that may cause adverse effects.

Secondary Prevention

There are abundant data to support the importance of effective secondary prevention—that is, prevention for patients with established CVD, such as ischaemic heart disease, PAD, or cerebrovascular disease. Following a cardiovascular event, there is clear evidence that optimisation of treatments to reduce risk factors—including for raised cholesterol—has a role to play.¹⁸ As part of secondary prevention, best practice for raised cholesterol involves high-intensity treatment with a statin and addition of second-line drugs if low-density lipoprotein (LDL) cholesterol targets are not reached.¹ A revision of CG181’s recommendations on secondary prevention is in progress, and is scheduled for publication in December 2023.¹⁹ 

Have Previous NICE Recommendations on the Treatment of Raised Cholesterol Been Fully Implemented?

When updating CG181, the members of the GDC were aware of ways in which the existing guidance was not being fully put into practice—notably, as of 2021, only 45% of people with a QRISK^® score of 10% or more were estimated to be receiving lipid-lowering therapy (LLT), rising to 56% for those with a QRISK^® score of 20% or more.^1,18 In light of this, the GDC discussed how pushing the recommendations of the update to the limits of the evidence would have made it even more challenging to implement (see QRISK^®3 Threshold for Initiation of Statin Therapy).^1,18 A pragmatic view was taken by the GDC that if we could, by virtue of this update, get to where we wanted to be with the previous guidance, that would in fact represent progress.^1,18 

The committee therefore spent a long time focusing on the language of certain recommendations to ensure that individuals who would benefit from preventive treatment were not being denied it, and also that the guideline would not be overly challenging to implement.^1,18 This was important, as we were aware that every instance for which we recommended prescribing a statin would create a small extra resource requirement in the form of blood tests, monitoring, and treatment optimisation.^1,18 We considered the final updated guideline to be a modest addition to practices’ workloads, whereas if we had rigidly followed the evidence, the additional workload could have been considerable.^1,18 This approach would not have been realistic given current resources in the primary healthcare system.^1,18 

Thus, in this update to CG181, the GDC aimed to make practical considerations when updating recommendations, based on the idea that NICE guidelines can be enacted more fully if they are made simpler to implement. To this end, part of the process was to identify potential barriers to implementation and ways in which the guideline could be simplified to make it more implementable.

Dr Joseph Mills—Overcoming Barriers to Implementation

What Are the Barriers to Implementing Recommendations on Statins in CG181?

Many barriers to the implementation of recommendations around statins in CG181 were identified in the GDC’s discussions and were considered throughout committee meetings when we were putting the guidance together. These barriers can be examined in a structured way.

At the National Level

The 2023–2024 operational planning guidance, which is sent each year to integrated care boards (ICBs) and local authorities to help them plan their commissioning strategy, still cites the following target for LLT as part of primary prevention of CVD: ‘Increase the percentage of patients aged between 25 and 84 years with a CVD risk score greater than 20 percent on [LLTs] to 60%’.²⁰ This differs from NICE guidance, which recommends treatment with 20 mg atorvastatin for primary prevention in patients with a 10-year QRISK^®3 score of 10% or more (see Box 1).¹ NICE’s recommendation is also supported by the 2023–2024 requirements of the Primary Care Network (PCN) Directed Enhanced Service.²¹ This disconnect between different strategic and operational guidance from NHS England and clinical advice from NICE has the potential to create uncertainty at both the professional and public levels.

Regarding secondary prevention, implementation of LLT is relatively high. According to the latest CVDPREVENT data published in March 2023, over 80% of patients with established CVD are receiving LLT for secondary prevention, as opposed to just under 50% of patients with a 10-year QRISK^® score of 10% or more but without established CVD.²² However, these data do not cover the intensity of LLT, and a significant problem is the lack of an agreed target lipid level for primary care to work towards. High-intensity LLT is required for secondary prevention—NICE recommends that people with CVD should start statin treatment with 80 mg atorvastatin¹—and, in my experience, the absence of a clear lipid target, coupled with the strain on primary care, has left practices unable to prioritise the optimisation of LLT. 

That said, a further update to CG181 is scheduled for December 2023 that will clarify NICE’s recommended lipid targets for secondary prevention of CVD.¹⁹ Furthermore, new Quality and Outcomes Framework (QOF) indicators were introduced in March 2023 to incentivise practices to review secondary prevention (see Table 1);^23,24 therefore, GPs are now more likely to be treating patients with established CVD to a non-high-density lipoprotein cholesterol target of 2.5 mmol/l or less and an LDL cholesterol target of 1.8 mmol/l or less. Although only recently introduced, this will hopefully increase the priority that primary care places on secondary prevention.

Table 1: QOF Indicators for 2023/24—Cholesterol Control and Lipid Management²³

At the Regional Level

In my opinion, although the effects of the COVID-19 pandemic cannot be underestimated, the successful implementation of CG181 has been made significantly more challenging by the restructure of the NHS and the inherent uncertainty that always accompanies such changes in governance. The restructuring of commissioning and the creation of integrated care systems (ICSs) and ICBs has made it harder to understand how services are commissioned. Cardiac networks did not exist until relatively recently,²⁵ so there has been no structured professional guidance body available to advise commissioning groups. In addition, funding streams are limited for regional structures: many ICSs are in deficit,²⁶ and there is minimal funding available to invest in CVD prevention. In some regions, prevention of CVD is simply not a priority.

At the Local Level

Perhaps the principal issue at a local level, which consists of local authorities and PCNs, relates to vascular health checks for identification of cardiovascular risk and primary prevention. Local authorities have a remit to arrange the delivery of vascular health checks, through the NHS Health Check programme, to people aged 40 years and older who are not already on a CVD register.^27,28 However, despite the benefits this service provides in identifying people who need primary prevention, this is not being delivered in a structured way—delivery is not even consistent within regions, let alone across the country—and uptake is poor.^6,27

At the Practice Level

Barriers at the GP level primarily come down to the competing priorities of a practice. In my experience, primary prevention of CVD may not be a priority and some practices do not have the time and resources to have conversations with patients that will provide the kind of person-centred care recommended in this guideline. The review of patients after lifestyle changes have been attempted appears to have been implemented to some degree, but this varies between practices. 

Ultimately, although the guidance does provide the structure and information clinicians need, it takes time to implement these key recommendations. In addition, some primary care practitioners lack some of the knowledge and skills necessary to provide such detailed assessments and interventions.  

At the Patient Level

In the GDC’s discussions, the patient representatives reported that there is a lot of confusion and uncertainty among the general public about statin therapy.¹⁸ Much of this can be attributed to media coverage that sensationalises the negative aspects of statin treatment and focuses on the effects on quality of life of unpleasant, relatively rare and less serious side effects, without offering a balanced view of the benefits.^29,30 Some primary care practitioners are hesitant to recommend statin therapy,¹ perhaps sharing some of the public’s misgivings about side effects or not fully understanding the magnitude of benefit. Inconsistent endorsement of the guidance by primary care may also be contributing to the public’s uncertainty about the benefits of statin therapy.

As a demonstration, see Box 2 for a comparative analysis of public engagement with the treatment of two risk factors for CVD: hypertension and raised cholesterol.

The Lack of a CVD Prevention Workforce

At all levels of the health service, one of the most significant obstacles to the delivery of CG181 is the lack of a dedicated CVD prevention workforce. CVD prevention is almost too big and complex an issue for any workforce, particularly one that is overstretched and coping with the many acute issues currently facing the NHS. There are various ongoing national initiatives regarding CVD—notably the NHS Health Check programme, the Cardiac Pathways Improvement Programme, Heart UK’s Tackling Cholesterol Together initiative, and the CVD Prevention Recovery Programme³³—but there is no national strategy concerning a dedicated CVD prevention workforce, and that is arguably the biggest problem we face at the moment.

In Light of These Barriers, How Was CG181 Adapted to Enhance Its Implementability?

A significant amount of the update was dedicated to reviewing the evidence on statin-related side effects, how frequent they are, and the degree of certainty that they are caused by the statin.^1,18 We tried to emphasise in the updated guideline that muscle aches and pains are common symptoms in the general population, but are only infrequently due to statin therapy. Statin use causes muscle pain in only around 1–2% of patients—meaning that, of the estimated 16% of people taking high-intensity statins who experience muscle pain, approximately one in 12 cases can be attributed to the statin.^1,18

When patients read negative coverage of the side effects of statins and believe they will have side effects, they may notice muscle pain more readily and attribute muscle pain of any cause to the statin—a phenomenon called the ‘nocebo effect’. Although clinicians may be tempted to dismiss this psychological effect, it can become a problem when a patient experiences it and stops adhering to therapy. 

In light of these considerations, the updated guideline advises clinicians to measure patients’ creatine kinase levels (see Box 1): if the results are no greater than five times the upper limit of normal, then it is unlikely that the symptoms are related to the statin, and the patient should be encouraged to continue their treatment.¹

Although the guideline can only do so much to combat negative perceptions of statins, promotion of its analysis of the evidence may help to change patients’ and clinicians’ views from ‘These are drugs that aren’t hugely beneficial, but have a whole array of nasty side effects’ to ‘These are drugs that are fantastically effective, extremely inexpensive, actually incredibly well tolerated, and have a huge impact on improving lipid profiles far in excess of anything that can be achieved using lifestyle interventions.’ Hence, although the guideline document does talk extensively about the importance of addressing lifestyle and cardiovascular risk factors, its recommendations on statins reflect the fact that there is no readily available intervention, nonmedical or nonpharmacological, that will impact as favourably on someone’s lipid profile as statin therapy.^1,18 I think this is a message that is not very well appreciated or understood, hence why the update aims to highlight it.

Given Current Limitations in Workforce and Resources, What Compromises Had to Be Made? 

QRISK^® Threshold for Initiation of Statin Therapy

There was quite a lot of discussion among the GDC about the workload implications of the recommendations, given the strain that primary care is currently under, and the GDC did make a compromise related to QRISK^® score. In the 2014 version of this guidance, the threshold for conducting a discussion about statin therapy was reduced from a QRISK^® score of 20% or more to 10% or more.^1,34 Because statin therapy is cost effective at every risk level, the GDC considered further lowering the threshold to a QRISK^® score of 7.5% or more in the 2023 update.³⁴ Indeed, other guidelines from around the world use more stringent targets.³⁵ However, the GDC was concerned about the increase in workload for primary care incurred by this change, so the 10% threshold was retained with the added recommendation that, if a patient with a QRISK^® score below 10% wishes to be considered for a statin—perhaps they have a strong family history of CVD, or other medical risk factors—clinicians can still offer this to them (see Box 1).¹ 

What Can Primary Care Do to Ensure that the Recommendations Are Fully Implemented?

Regarding annual review, the GDC felt that primary care needed to endorse a process that fosters patient adherence.¹ Many people stop their statins within the first year,³⁶ so it was agreed that an annual review should reinforce the importance of therapy, but also reassess risk to ensure that therapy is still required¹—maybe the patient has totally transformed their risk profile, for example, and no longer requires a statin. This review is an opportunity, from both a patient and a professional perspective, to improve the quality of care.

In the guideline, it is stated that practices should provide an annual review to patients taking statins (see Box 1), and the GDC acknowledged that this would increase the workload of primary care.^1,18 Yet, as a committee of experts, the GDC was aware that it was suggesting an ideal pathway with this recommendation, accepting that it may not always be achievable but saying that to ignore and undervalue it would be wrong.

Resource Use and Workforce Pressures

Different practices have different pressures and resources: they may have a fleet of healthcare assistants or practice nurses who are really interested in prevention, or—at the other end of the scale—they may find that delivering even basic health checks is challenging. In general, practices are not financially incentivised and reimbursed for prevention in the same way that they are for treating disease, and it is therefore going to cost money rather than save money to improve the health of local populations in this way. Furthermore, the benefits will primarily be felt in acute care, perhaps many years down the line, so it is difficult for GPs and practice owners—who are, after all, running a business—to organise and deliver these interventions. 

Nonetheless, there are ways in which practices and PCNs can work on CVD prevention that do not require new funding or added workload, particularly involving staff employed through the Additional Roles Reimbursement Scheme. See Box 3 and Figure 1 for examples of innovative ways of delivering vascular health checks and lipid management in primary care—Box 3 gives details of a health and wellbeing coach-led service for the delivery of vascular health checks, and Figure 1 shows the patient journey through a lipid management pathway led by pharmacists and healthcare assistants.

Figure 1: Lipid Management in Devon: Pharmacist and Healthcare Assistant-Led Service

QOF Targets 

As mentioned previously, new QOF targets were introduced in March 2023 to financially incentivise practices to improve secondary prevention of CVD (see Table 1).^23,24 Although primary care is already inundated with targets, this move does allocate funding to secondary prevention activities and may enable more practices to optimise LLT in patients with CVD. Similarly, the QOF or indeed the Investment & Impact Fund could align with NICE’s recommendations on primary prevention in CG181 by incentivising general practice to offer statin therapy to individuals with a CVD risk score of 10% or more.

Summary

Disease prevention is a complicated area of healthcare that is significantly affected by economic and social considerations. Changing national strategies and structures, conflicting financial considerations, workforce pressures, and public perception all have a part to play when guidelines are being produced and implemented, and compromises have to be made. This is particularly true for a consideration as large as CVD—a leading cause of mortality and morbidity worldwide.

Some useful resources for clinicians and patients are included in the ‘Useful Resources’ box.