- Manage lipids and other cardiovascular (CV) risk factors based on absolute cardiovascular disease (CVD) risk assessment.
- Base the decision to begin lipid-modifying treatment on the patient’s absolute CV risk.
- Be aware that not all patients with dyslipidaemia require lipid-modifying medicines and some patients who need lipid-modifying medicines may not have dyslipidaemia.
Statins remain a foundation of lipid management due to their well-established efficacy at preventing vascular events.1-3 Despite this proven efficacy and safety, use of statins in clinical practice, and adherence to these medicines by patients, is not optimal.
Evidence suggests statin medicines are being prescribed for patients with elevated cholesterol but low absolute CV risk and underused by patients with high CV risk.4-6 This means that some patients are unnecessarily treated, while others are not receiving necessary treatment.
Absolute cardiovascular risk
A patient’s absolute CV risk is their likelihood of experiencing a cardiovascular event within a defined period. For Australian guidelines, this is within the next 5 years.4,7
Assessing risk, using validated Australian CVD risk charts or associated web calculator, is an important first step in determining whether a patient should be prescribed a lipid-modifying medicine or not. The use of an absolute CV calculator can support appropriate treatment options being delivered, leading to improved CV risk management and CV outcomes.4 Evidence also indicates that GPs who used absolute risk calculators are more likely to correctly identify risk factors for CVD, compared to those who decided to treat based on individual risk factors.8
Guidelines recommend calculating absolute CV risk for patients who are aged 45–74 years and Aboriginal and Torres Strait Islander adults aged 35–74 years, who are not known to have CVD or not already known to be at clinically-determined high risk of CVD (see below).4,7 Those in the latter group do not need a formal risk calculation as they are already known to be at high risk.
Health professionals should be aware that the predictive value of the risk equation has not been assessed in overweight or obese populations and may underestimate the CVD risk in some groups including socioeconomically disadvantaged groups, people with depression and people aged > 74 years.4
People known to be at high CV risk4
People with any of the following risk factors are already known to be at high risk of a CV event and do not require risk calculation:
- established CVD
- diabetes and age > 60 years
- diabetes with microalbuminuria (more than 20 micrograms/min, or urinary albumin:creatinine ratio > 2.5 mg/mmol for males or > 3.5 mg/mmol for females)
- moderate or severe chronic kidney disease (persistent proteinuria or eGFR < 45 mL/min/1.73 m2)
- a previous diagnosis of familial hypercholesterolaemia
- systolic BP ≥ 180 mmHg, or diastolic BP ≥ 110 mmHg
- serum total cholesterol > 7.5 mmol/L
- Aboriginal and Torres Strait Islander adults aged > 74 years
Who benefits the most from therapy?
Statins are the most effective oral lipid-modifying medicines and are the first-line treatment for LDL-C lowering.4 They reduce the risk of cardiovascular events and death for people at high risk of CVD and are effective in both primary and secondary prevention, in men and women, across all age groups.2,4,9
Each 1.0 mmol/L reduction in LDL-C with statin treatment reduces the risk of major vascular events by 20% in primary prevention and 25% in secondary prevention.1 Risk of serious long-term adverse effects associated with use of statins is low.7,10
The AusHEART study suggests that up to 30% of patients at low absolute CV risk are being prescribed a statin.5 However, this group of patients receive the least absolute benefit from lipid-modifying (and BP-lowering) medicines, and harms are likely to outweigh the benefits of treatment in many of them. It is generally recommended not to prescribe lipid-modifying medicines for these patients.4,5,11
Patients identified as high CV risk should be prescribed a lipid-modifying medicine. These patients receive the greatest absolute benefit from statins, and include those who have had a previous CV event (secondary prevention).1,12 Additionally, a modelling study, cited by the National Vascular Disease Prevention Alliance, indicated that treating those at highest absolute risk is potentially more than twice as effective in reducing death from coronary heart disease than treating people with elevated cholesterol levels alone.13,14 Based on meta-analysis data of 27 clinical trials, authors predicted that 5 years of statin therapy that reduces LDL-C by 2.5 mmol/L has the potential to: prevent 100 major vascular events per 1000 people treated in patients with ≥ 20% to < 30% absolute CV risk compared to 12 events per 1000 in patients with <5% risk.1
When lipid modifying medicines are indicated, patients are usually started on a low dose of a statin which is titrated (if necessary) until target lipid levels or maximum tolerated dose (MTD) are achieved.4 In patients who have had a previous CV event, statins are usually started at a higher intensity (dose + potency) with lower LDL-C targets.15-17 The maximum response to a dose can usually be observed within 4 weeks of initiation or dose increase.7 Statin monotherapy should be trialled adequately which involves optimising adherence to medicine and lifestyle changes as well as titrating to MTD. If patients are persistently not meeting targets with optimal monotherapy, consider:7,18
- assessing adherence to medicines and discuss its importance
- increasing the dose or switching to an alternative more potent statin7
- discussing the importance of adherence to lifestyle modifications.
When to add a second-line lipid-modifying medicine
Consider adding a second lipid-modifying medicine if target LDL-C levels are not being achieved with the maximum tolerated dose of a statin.7 Consider ezetimibe or a PCSK9 inhibitor (eg, evolocumab) second-line after statins.7 Ezetimibe is associated with further LDL-C reductions of 20%–25% when added to statin treatment. Therapeutic Guidelines highlights that whilst bile acid binding resins, fibrates and nicotinic acid have been shown to improve lipid abnormalities, there is limited evidence to support adding them to statin treatment to improve cardiovascular outcomes.7
Who needs alternatives to statins?
- Consider non-statin lipid-modifying medicine(s) for:4,7
- those who cannot tolerate a statin (be sure to determine true intolerance)
- those with predominantly elevated triglycerides
- some patients with mixed hyperlipidaemia
- those who need adjuvant treatment because they cannot reach LDL-C targets with the maximum tolerated dose of a statin following an adequate trial.
The importance of adherence
Patient non-adherence to lipid-modifying medicines is a key reason for lipid targets not being met and remains a concern in clinical practice. It has been established that up to 67% of patients are non-adherent to statins as prescribed after 12 months.19 Patients who do not adhere to lipid-modifying medicines have an increased risk of CVD mortality or may be at increased risk of higher all-cause mortality, hospitalisations and revascularisations.19
Non-adherence can be intentional or unintentional.20 With intentional non-adherence the patient decides to stop or change their agreed treatment regimen, often after balancing the benefits (eg, improved quality of life) against the risks (eg, the adverse effects associated with treatment). When a patient wants to follow the agreed regimen but is prevented by barriers beyond their control, this may be described as unintentional non-adherence.
The table below outlines some strategies that may help to target and reduce barriers to adherence.20
Consider asking these questions
Beliefs and attitudes about medicines
How do you feel about taking these medicines?
Have you ever thought about changing your medicines?
How well does the medicine work for you?
Consider motivational counselling
Provide verbal and written counselling on the following:21
How are you going with those tablets?
How have you been taking these medicines?
Discuss the patient’s medicines regimen and tailor it to their daily activities – some statins may be more effective if they are taken in the evening, however consider convenience first18
Simplify the regimen by suggesting combination therapy, if appropriate
Suggest adherence packages (eg, dose administration aid)
Offer generic equivalents where cost is an issue
People often have difficulty using their medicines, and I am interested in finding out any problems that occur so that I can understand them better. Do you ever miss taking your medicine? How often?
It must be hard trying to remember to take the tablets every time. Do you ever forget? How do you feel about that?
Discuss practical strategies such as:
Review adherence to medicines and lifestyle regularly (eg, at every consultation), especially before changing lipid-modifying medicines,18 and consider providing resources that explain CVD and statins (eg, print out information from reputable websites). The MedicineWise app may be useful to help remind patients to take their medicine and to refill prescriptions.
Statin-associated muscle symptoms
Statin-associated muscle symptoms (SAMS) have been reported as a key contributing factor to statin non-adherence – in 65% of former statin users, the main reason for statin non-adherence or discontinuation was onset of side effects, predominantly muscle-related effects.23
Observational studies in clinical practice have shown SAMS are perceived as a common side effect among people receiving statin therapy (7%-29%).9,23,24 However, randomised controlled trial data suggests the true incidence of SAMS may not be as high (1%-5%).25-27 Assessing and confirming the diagnosis of true statin-associated muscle symptoms can help to maximise the benefits of statin therapy for people at high absolute CV risk, and avoid unnecessary medicine changes.
In 2015, NPS MedicineWise collaborated with clinical experts to develop a SAMS assessment guide and a SAMS management algorithm to support management of patients with suspected muscle symptoms in primary care. Additional materials developed as part of this program include the health professional mediated action plan Staying on track with your statin and a factsheet answering common consumer questions regarding statin medicines.
- Cholesterol Treatment Trialists' Collaborators. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet 2012;380:581-90.
- Collins R, Reith C, Emberson J, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet 2016.
- Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2013:Cd004816.
- National Vascular Disease Prevention Alliance. Guidelines for the management of absolute cardiovascular disease risk. 2012 (accessed 23 September 2021).
- Heeley EL, Peiris DP, Patel AA, et al. Cardiovascular risk perception and evidence--practice gaps in Australian general practice (the AusHEART study). Med J Aust 2010;192:254-9.
- Jansen J, Bonner C, McKinn S, et al. General practitioners’ use of absolute risk versus individual risk factors in cardiovascular disease prevention: an experimental study. BMJ Open 2014;4.
- Therapeutic Guidelines Ltd (eTG March 2021 edition). Lipid modifiation. West Melbourne: Therapeutic Guidelines Limited, 2018 (accessed 20 September 2021).
- Imms A, Quinn S, Nelson M. General practitioners’ use of cardiovascular risk calculators. Aust Fam Physician 2010;39:57-60.
- Catapano AL, Graham I, De Backer G, et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. Eur Heart J 2016;37:2999-3058
- Ward NC, Watts GF, Eckel RH. Statin Toxicity. Circ Res 2019;124:328-50.
- Doust J, Sanders S, Shaw J, et al. Prioritising CVD prevention therapy Absolute risk versus individual risk factors. Aust Fam Physician 2012;41:805-9.
- Chou R, Dana T, Blazina I, et al. Statins for prevention of cardiovascular disease in adults: Evidence report and systematic review for the us preventive services task force. JAMA 2016;316:2008-24.
- Manuel DG, Kwong K, Tanuseputro P, et al. Effectiveness and efficiency of different guidelines on statin treatment for preventing deaths from coronary heart disease: modelling study. BMJ 2006;332:1419.
- Manuel DG, Lim J, Tanuseputro P, et al. Revisiting Rose: strategies for reducing coronary heart disease. BMJ 2006;332:659-62.
- Chew DP, Scott IA, Cullen L, et al. National Heart Foundation of Australia & Cardiac Society of Australia and New Zealand: Australian Clinical Guidelines for the Management of Acute Coronary Syndromes 2016. Heart Lung Circ 2016;25:895-951.
- National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand. Reducing risk in heart disease: An expert guide to clinical practice for secondary prevention of coronary heart disease. Melbourne: National Heart Foundation of Australia, 2012. [Online] (accessed 23 September 2021)
- National Institute for Health and Care Excellence. Lipid modification: Cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. Clinical Guideline. NICE, 2014. [Online] (accessed 20 February 2017).
- Australian Medicines Handbook. Drugs for dyslipidaemia. Adelaide: Australian Medicines Handbook Pty Ltd, 2021 (accessed 23 September 2021).
- Turin A, Pandit J, Stone NJ. Statins and nonadherence: Should we RELATE better? J Cardiovasc Pharmacol Ther 2015;20:447-56.
- National Heart Foundation of Australia (Aslani P KI, Bajorek B, Thistlethwaite J,, Tofler G on behalf of the Heart Foundation Pharmaceutical Roundtable). Improving adherence in cardiovascular care: A toolkit for health professionals. 2011 (accessed 20 September 2021).
- Eussen SR, van der Elst ME, Klungel OH, et al. A pharmaceutical care program to improve adherence to statin therapy: a randomized controlled trial. Ann Pharmacother 2010;44:1905-13.
- Derose SF, Green K, Marrett E, et al. Automated outreach to increase primary adherence to cholesterol-lowering medications. JAMA Intern Med 2013;173:38-43.
- Stroes ES, Thompson PD, Corsini A, et al. Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur Heart J 2015;36:1012-22
- Bruckert E, Hayem G, Dejager S, et al. Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients--the PRIMO study
- Ganga HV, Slim HB, Thompson PD. A systematic review of statin-induced muscle problems in clinical trials. Am Heart J 2014;168:6-15.
- Parker BA, Capizzi JA, Grimaldi AS, et al. Effect of statins on skeletal muscle function. Circulation 2013;127:96-103.
- Rosenson RS, Baker SK, Jacobson TA, et al. An assessment by the Statin Muscle Safety Task Force: 2014 update. J Clin Lipidol 2014;8:S58-71.