Dr Alan Begg describes amendments to the recently updated NICE key therapeutic topics for lipid-modifying drugs, with key changes relating to statin use
Read this article to learn more about:
- why key therapeutic topics are important and how they are developed
- recent updates to key therapeutic topics for lipid-modifying drugs
- the importance of lipid-lowering drugs, such as statins and ezetimibe, in managing long-term conditions.
The most recent list of key therapeutic topics (KTTs), entitled 'Medicines management options for local implementation' (see Table 1, below), was published by NICE on 15 January 2015.1 This document was produced by the Medicines and Prescribing Centre at NICE (part of its Centre for Clinical Practice) and although the KTTs may reflect evidence-based guidance from NICE, they are not formal NICE guidance. The 14 topics from the January 2013 publication have been retained and updated on the basis of recently published new evidence and guidance.
Why key therapeutic topics?
Key therapeutic topics are developed to support medicines optimisation but are only published after a consultation process and feedback from the NHS and partner organisations. Their aim is to support the implementation of NICE guidance, either directly or by signposting the NHS to therapeutic evidence or prescribing practice relevant to existing practice. The topics are therapeutic areas where there are potential opportunities for maintaining or improving quality and value so that resources can be released from one area of healthcare for use elsewhere.
What is QIPP?
Quality Innovation Productivity and Prevention (QIPP) is described as a large scale transformational programme for the NHS with national work streams designed to support the achievement of a number of quality and productivity challenges.2 The Health and Social Care Information Centre (HSCIC) leads on, and is responsible for, the development of QIPP comparators for these KTTs. The Government's white paper entitled 'Equity and excellence: liberating the NHS'3 outlined its commitment to ensure that QIPP supports the NHS to make efficiency savings for reinvestment into the service with the aim of continually improving the quality of care. Not every KTT has a comparator because currently available prescribing data may not be available to provide meaningful comparisons.
How are key therapeutic topics developed?
Key therapeutic topics are targeted at clinicians and local medicines optimisation services across all areas of the NHS. Box 1 (see below) highlights the identification, prioritisation, and selection criteria for KTTs.2 Based on these criteria, the Department of Health's QIPP Wider Reference Group (WRG) prioritises KTTs and, after considering feedback, the final list of topics is produced by the NICE Medicines and Prescribing Centre and confirmed by the NICE executive.2 The content of each topic should be fair, balanced, and accurately reflect the evidence reviewed. It should also be substantiated by an explicit and appropriate source of evidence.
|KTT2||Renin-angiotensin system drugs|
|KTT4||Omega-3 fatty acid supplements|
|KTT5||High-dose inhaled corticosteroids in asthma|
|KTT7||Low-dose antipsychotics in people with dementia|
|KTT8||First-choice antidepressant use in adults with depression or generalised anxiety disorder|
|KTT9||Antibiotic prescribing—especially broad spectrum antibiotics|
|KTT10||Three-day courses of antibiotics for uncomplicated urinary tract infection|
|KTT12||Type 2 diabetes mellitus|
|KTT13||Non-steroidal anti-inflammatory drugs|
|KTT14||Wound care products|
NICE (2015). Medicines management options for local implementation. Reproduced with permission.
Box 1: Identification, prioritisation, and selection criteria for key therapeutic topics
Therapeutic topic with a potential opportunity for improving quality, innovation, productivity or prevention because of:
- a safety issue or risk:benefit issue
- large productivity savings
- large variations in clinical practice with data demonstrating under usage or over usage
- a positive technology appraisal
- potential opportunity to prevent the development of illness or complications, including by reducing service utilisation (for example, admissions)
- high clinician or patient interest.
NICE (2015). Medicines management options for local implementation—integrated process statement. NICE article. Reproduced with permission.
NICE Guideline (NG) 5 on Medicines optimisation: the safe and effective use of medicines to enable the best possible outcomes was published in March 20154 (a summary of the guideline can be found on the Guidelines website). In 2012, 15 million people in England had a longterm condition (LTC), with one half of the population over the age of 60 having a LTC.4,5 As LTCs account for around one half of all GP appointments there is an increased need to ensure appropriate polypharmacy where medicine use has been optimised.6 This would help to counteract problematic polypharmacy where there has been inappropriate prescribing or where the intended benefits of medicines are not realised.
According to NICE NG5,4 the key priorities for implementation relate to the following topics:
- systems for identifying, reporting, and learning from medicines-related patient safety incidents
- medicines-related communication systems when patients move from one care setting to another
- medicines reconciliation.
Medicines reconciliation should ideally be carried out by a pharmacist, pharmacy technician, nurse or doctor with the necessary skills; these include the technical knowledge of processes for managing medicines, and a therapeutic knowledge of medicines' use.
Key therapeutic topic for lipid-modifying drugs (KTT3)
The use of lipid-lowering drugs plays an important role in managing LTCs, therefore revisions of this KTT concerning lipid-modifying drugs (primarily statins and ezetimibe) are important for general practice. This KTT has been revised in accordance with the updated NICE Clinical Guideline 181 on lipid modification, published in July 2014 (last modified January 2015), but also relates to other guidance covering type 1 and type 2 diabetes and chronic kidney disease (CKD).8–10
Statins are grouped into three categories according to their intensity:1
- low intensity: 20–30% low-density lipoprotein cholesterol (LDL-C) reduction; fluvastatin 20–40 mg daily, pravastatin 10–40 mg daily, simvastatin 10 mg daily
- medium intensity: 31–40% LDL-C reduction; atorvastatin 10 mg daily, fluvastatin 80 mg daily, rosuvastatin 5 mg daily, simvastatin 20–40 mg daily
- high intensity: >40% LDL-C reduction; atorvastatin 20–80 mg daily, rosuvastatin 10–40 mg daily, simvastatin 80 mg daily.
NICE recommends a starting dose of 80 mg atorvastatin for secondary prevention of cardiovascular disease (CVD) but an initial dose of 20 mg in those individuals with CKD.1 In primary prevention, if the QRISK2 10‑year CVD risk assessment score is 10% or greater, then 20 mg atorvastatin is recommended for cholesterol lowering.1
The decision to commence a patient on a statin should be made after an informed discussion covering the risks and benefits, with the following additional factors taken into account:
- potential benefits from lifestyle modifications
- informed patient preference
- general frailty
- life expectancy.
A full clinical assessment and blood tests should be undertaken before commencing statin treatment and the effect should be measured in all patients started on high intensity statins after 3 months of treatment. In those patients not achieving a great enough (>40%) reduction in non-high density lipoprotein (HDL) cholesterol, it is important to discuss adherence and the timing of the statin dose, as well as optimising adherence to diet and lifestyle measures.1 The dose of atorvastatin can be increased to 80 mg using clinical judgement and if the patient is judged to be at higher risk because of co-morbidities.1
In the event of patient intolerance to a high-intensity statin, the aim should be to treat with the maximum tolerated dose.1 Other advice includes:1
- stopping the statin and then re‑challenging when the symptoms have resolved to check if the symptoms are related to the statin
- reducing the dose within the same intensity group
- changing the statin to a lower intensity group.
Choice of statin
Clinicians are advised that a statin of high intensity and low acquisition cost should be chosen. For those patients on a lower dose statin, NICE recommends a medication review with the patient to discuss the likely benefits and potential risks of changing to a higher intensity statin.1 Simvastatin 80 mg is associated with an increased risk of myopathy, so this dose should only be used in exceptional circumstances, where there is no alternative and the benefits are expected to outweigh the potential risk.1
Citing the SATURN trial, which compared atorvastatin and rosuvastatin, the NICE guideline stated that because of its higher cost, rosuvastatin would need to be considerably more effective to allow it to be recommended.1 Despite this advice for its use in the UK, last year, rosuvastatin was the most prescribed brand name drug in the US with worldwide 2013 sales being the third highest for any branded drug.11
Ezetimibe inhibits the Niemann-Pick C1-like 1 protein, located primarily on the epithelial brush border of the gastrointestinal (GI) tract, resulting in reduced cholesterol absorption.8 The drug can be used in heterozygous-familial or non-familial hypercholesterolaemia and as an alternative to statins in two broad situations: it can be used in patients in whom statins are contraindicated or not tolerated, as well as in addition to a statin when cholesterol reduction is inadequate. This especially applies if titration is limited by intolerance and consideration has been given to prescribing an alternative statin.1
The KTT did not consider the results of the IMPROVE-IT study, which compared ezetimibe 10 mg/simvastatin 40 mg with simvastatin 40 mg in patients stabilised after an acute coronary syndrome episode. Although presented at the time of publication of the KTT, the trial results will not be formally published until May 2015.12 In relation to the primary endpoint of cardiovascular death, myocardial infarction, documented unstable angina requiring hospitalisation, coronary revascularisation (≥30 days after randomisation), or stroke, the combination therapy was significantly more effective; p=0.016 (HR: 0.936; CI: 0.887–0.988). The event rate was 32.7% in the combination group compared with 34.7% in the simvastatin only group; the number needed to treat over 7 years being 50 to prevent an event.12 There was a similar benefit for the combination therapy in the pre-specified secondary end points.
Bile acid sequestants, fibrates, and nicotinic acid are not recommended for routine use alone or in combination with a statin for either primary and secondary prevention.1 Omega-3 fatty acids may have a specific role in reducing plasma triglycerides, but they are likewise not recommended for primary and secondary prevention.1
Data for the second quarter of 2014 reveals a 1.5-fold variation in statin prescribing rates at clinical commissioning group (CCG) level of low cost lipid modifying drugs. There was very little increase (0.3%) from the previous year in the comparator value but a 6% decrease in variation was observed over the same period. The comparator for percentage of ezetimibe items shows a 5.9-fold variation in prescribing rates but comparison with the previous year revealed a 10.2% decrease in comparator value and 9.5% decrease in variation.1
Annually, nearly half a million items of omega-3 fatty acid compounds are prescribed in primary care in England costing around £12 million with a 62.5‑fold variation in prescribing rates at CCG level.1
With the population living longer, the level of both LTCs and medicine use are set to increase. Medicines optimisation with appropriate polypharmacy is important so that patients benefit from reduced medicines-related patient safety incidents. Within the NHS there is constant pressure to save money by switching patients to marginally less expensive drugs. The effort that medicine management teams put into swapping drugs and chasing prices means that less time and fewer resources are available to support healthcare professionals undertake comprehensive medicines optimisation, which may improve outcomes for patients.13
Lipid-lowering drugs play a key role in managing LTCs. In line with the recently updated NICE guideline on lipid modification, KTT3 for lipid-modifying drugs including statins, ezetimibe, fibrates, nicotinic acid, and bile acid sequestrants has been updated. Key amendments considered important for general practice include choice and dose of statins, and how to deal with statin intolerance, as well as the use of ezetimibe as an alternative to statins in selected patients.
- KTTs reflect NICE guidance, but are not considered formal NICE guidance
- Previous KTTs have been retained and updated
- The KTT concerning lipid modifying drugs is important for general practice
- The choice of statin should be considered based on its LDL-C lowering intensity
- A statin of high intensity and low acquisition cost should be chosen
- Aim to treat with the maximum tolerated dose
- If statins are contraindicated or not tolerated, consider ezetimibe as an alternative
- Variation remains in the prescribing of lipid modifying drugs at CCG level.
KTT=key therapeutic topic; LDL-C= low-density lipoprotein cholesterol; CCG=clinical commissioning group
GP commissioning messages
written by Dr David Jenner, NHS Alliance GMS contract/PBC Lead
- NICE Clinical Guideline 181 on lipid modification and use of statins has proved controversial to many GPs in extending the recommendations for statin prescription in primary prevention
- the use of higher intensity statins for secondary prevention is well evidenced and less controversial and recommends atorvastatin, which is of low acquisition cost, for use in primary and secondary prevention
- although the IMPROVE-IT study has demonstrated some evidence of effectiveness for ezetimibe, use of this drug is usually discouraged by CCGs and is used as a marker of prescribing effectiveness in the Primary Care Web Tool
- when this study is formally published, CCG medicines optimisation teams may need to review the use of ezetimibe in CCG formularies as it was not considered by NICE
- With the renewed focus on NHS budgets, CCGs are likely to resist prescribing of rosuvastatin, which is of high acquisition cost and not recommended by NICE for first-line use
- Prescribing costs for 28 days:a
- simvastatin 20 mg, £1.02; 40 mg, £1.14
- atorvastatin 20 mg, £1.41; 40 mg, £1.59; 80 mg, £2.71
- rosuvastatin 10 mg, £18.03; 20 mg, £26.02; 40 mg, £29.69.
- NICE. Medicines management options for local implementation. Key therapeutic topics. NICE, 2015. Available at: www.nice.org.uk/Media/ Default/About/what-we-do/NICE-advice/ Key-therapeutic-topics/Key-therapeutictopics- 2015-1.pdf
- NICE. Medicines management options for local implementation—Integrated process statement. NICE, 2013. Available at: www.nice.org.uk/ article/pmg13/chapter/1%20introduction
- NHS Institute for Innovation and Improvement. Quality Innovation Productivity and Prevention (QIPP). NHS, 2010. Available at: www.institute.nhs.uk/cost_and_quality/qipp/cost_and_quality_homepage.html
- NICE. Medicines optimisation: the safe and effective use of medicines to enable the best possible outcomes. NICE Guideline 5. NICE, 2015. Available at: www.nice.org.uk/guidance/ng5
- Hobbs F, Baker M, Davies S. Morbidity matters: challenges for research. B J Gen Pract2015; 65 (633): 171–172.
- NHS England. Domain 2: Enhancing quality of life for people with long-term conditions. Available at: http://www.england.nhs.uk/resources/resources-for-ccgs/out-frwrk/dom-2/
- 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, 2004. 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
- Wolfe S. Rosuvastatin: winner in the statin wars, patients' health notwithstanding. BMJ 2015; 350: h1388.
- The European Atherosclerosis Society. Improved Reduction of Outcomes: Vytorin Efficacy International Trial. EAS 2014. Available at: www.eas-society.org/fileArchive/IMPROVE%20IT%20-%20PRESENTATION%202014-11-17.pdf
- Medicines optimisation in England: where are we now? Drug Ther Bull 2015; 53 (2): 13.