CVD risk: lipid management
Published in MedicineWise News
Date published: About this date
- Assess absolute cardiovascular disease risk early
- Consider the potential benefit to the patient when choosing a statin and determining dose
- Use ezetimibe in patients when a statin alone is inadequate or is not tolerated
- Discuss cardiovascular risk with the patient to encourage lifestyle changes
- Encourage long term adherence by regularly reminding patients of the benefits of lifestyle changes and lipid modifying therapy
Assess absolute cardiovascular risk early
Assess the absolute cardiovascular risk of everyone aged 45–74 years (Aboriginal and Torres Strait Islanders ≥ 35 years) without known increased risk, to identify if they could benefit from early intervention.1 Once a person has advanced atherosclerosis, drug therapy can reduce risk but not to the level of a person with minimal coronary lesions.2
Use a risk tool routinely for assessing people without cardiovascular disease
Risk tools are better than clinical judgement alone for assessing people without cardiovascular disease: they account for the combined effect of risk factors and can inform treatment decisions and motivate patients.3-6 People with cardiovascular disease or a known high risk condition (see Box 1) do not need a risk tool–based assessment.1
Use the Australian cardiovascular risk charts or web calculator (see www.nps.org.au/cvdrisktools for links) to estimate a risk score.1 Categorise risk according to the chance of a cardiovascular event in the next 5 years: low < 10%, moderate 10% to 15%, or high > 15%.
Treat the risk score as a starting point for full assessment
Cardiovascular risk tools do not account for all risk factors and can underestimate risk for Aboriginal and Torres Strait Islanders, Maori and Pacific Islanders, people from the Indian subcontinent, and people with diabetes aged 45–60 years.1-7 Identify all risk factors (see Box 2) — if a person is from a population in which risk may be underestimated, treat the score as a minimum estimate of risk.1
Base management on the individual’s risk score and lipid levels
People at high cardiovascular risk clearly benefit from a lipid-lowering drug together with lifestyle changes.8-11 The benefits of drug treatment diminish as absolute risk decreases: lifestyle changes and regular assessment are the priority for people at low cardiovascular risk (<10% chance of an event in 5 years).12
Box 1: Known high risk conditions1
- diabetes mellitus and age > 60 years or with microalbuminuria
- moderate or severe chronic kidney disease
- familial hypercholesterolaemia
- systolic blood pressure ≥ 180 mm Hg or diastolic blood pressure ≥ 110 mm Hg
- serum total cholesterol > 7.5 mmol/L
Discuss cardiovascular risk to encourage lifestyle change
Adherence to lifestyle changes is often poor, even after myocardial infarction.14 People who are better informed and involved in decisions about their own care are more likely to adhere to an agreed management plan.4
Show patients their risk score and explain its meaning
Providing absolute cardiovascular risk scores, particularly when combined with education and when repeated, helps people understand their risk and can motivate them to make lifestyle changes.3
Use visual aids to enhance people’s understanding of their cardiovascular risk (e.g. Your Heart and Stroke Risk Score).4 Show patients how modifying different risk factors can affect their score (e.g. use the web-based cardiovascular disease risk calculator to ‘compare’ different risk scenarios). Encourage patients to record and monitor their risk factors (e.g. Managing My Heart Health: At A Glance cards).
Box 2: Cardiovascular risk factors for assessment1,13
|Total and HDLA cholesterol (or their ratio)B
Waist circumference and body mass index
Physical activity level
Alcohol intake (risk factor for raised BP)
Left ventricular hypertrophy (if known)B
Socioeconomic status and mental health
Family history of early cardiovascular disease
Consider the potential benefits when choosing a statin and dose
Choose statins first line when a lipid-lowering drug is required
Statins are the most effective cholesterol-lowering drugs, they reduce cardiovascular event rates and death in people at increased cardiovascular risk (with or without established disease) and are well tolerated.15
Prescribe a statin with lifestyle changes for people at increased cardiovascular risk
Prescribe drug treatment for people with: cardiovascular disease; a known high-risk condition (see page 1); diabetes and who are an Aboriginal or Torres Strait Islander; a family history of very early coronary disease; a high risk score; or a moderate risk scoreC plus either metabolic syndrome or a family history of early coronary disease.8,12 People at greatest cardiovascular risk benefit the most from a statin.9,10,16 Lifestyle changes benefit people at any level of risk.15
Treat people with cardiovascular disease intensively: aim for an LDL target of < 2 mmol/L
Start people with stable cardiovascular disease on a statin dose that has a moderate LDLD cholesterol–lowering effectE (e.g. simvastatin 40 mg), then treat to an LDL cholesterol target < 2 mmol/L.4,7 Consider starting people with acute coronary syndrome on a statin dose that has a greater LDL-lowering effect (e.g. atorvastatin 80 mg).4 Use the target LDL cholesterol level as a guide4 — intensive LDL lowering is beneficial for people with cardiovascular disease even if the target cannot be met.18,19
Monitor closely for muscle effects and liver enzyme elevations when prescribing high doses of statins as these adverse effects are dose-related (see Statin-induced myopathy is rare).20
Treat people without cardiovascular disease to an LDL target of < 2.5 mmol/L
Start people without cardiovascular disease on a statin dose that has a moderate LDL-lowering effect.4,5,7 In major trials, regimens included simvastatin 40 mg10, atorvastatin 10 mg21, or pravastatin 40 mg.22 These regimens lowered LDLD cholesterol levels by about 30% to 40%, reduced the relative risk of major coronary events by about 25% to 35%, and were generally well tolerated.10,21-23 The recommended starting dose of rosuvastatin is 5–10 mg24; while rosuvastatin 20 mg lowered LDL cholesterol by about 50% and reduced cardiovascular events in a large primary prevention trial, the long-term safety of this regimen has not been established in this population.25
When reviewing LDL levels and statin dosage, take into account absolute cardiovascular risk and if greater gains can be had from treating other risk factors. No trials have compared moderate LDL-lowering with more intensive regimens in people without cardiovascular disease.4
Use ezetimibe if a statin alone is inadequate or not tolerated
Ezetimibe is one of several lipid-modifying drugs that can be used for people who cannot tolerate a statin, or can be added to a statin when targets have not been met. Ezetimibe increases the LDL lowering effect of a statin (by up to 20%) and as monotherapy lowers LDL cholesterol by about 18%.15 However, there are limited data on its efficacy in improving cardiovascular outcomes. No trials have shown that ezetimibe monotherapy reduces cardiovascular events. Recent results suggest that ezetimibe plus simvastatin reduces the risk of vascular events in people with chronic kidney disease compared with placebo26, but importantly there are no trial data to show that ezetimibe plus a statin is more effective than a statin alone.
Bile-acid-binding resins reduce LDL cholesterol by about 15% to 25% and there is evidence that cholestyramine improves cardiovascular outcomes.15
Fibrates (gemfibrozil, fenofibrate) and nicotinic acid reduce LDL cholesterol (gemfibrozil less so), but have a more marked effect on triglycerides and HDL cholesterol.15 The effect on cardiovascular event rates of combined therapy with any of these agents and a statin has not been established.
Reserve non-statin lipid-modifying drugs for:
- people unable to take statins due to contraindications or clinically-important adverse effects
- combination with a statin when higher statin doses do not adequately reduce LDL cholesterol or are not tolerated. Avoid combining a statin with gemfibrozil or nicotinic acid, and as these combinations can increase the risk of myopathy.12
Muscle pain or discomfort is common in people taking statins, but myopathy is rare, particularly in the absence of risk factors.5
Muscle symptoms were reported at a rate of 1.5% to 3% in both statin and placebo groups in trials.27 Higher rates have been reported in practice, probably because trials excluded people with risk factors or intolerance.27 Myopathy was reported in trials with simvastatin in 0.02%, 0.08% and 0.6% of people who received 20, 40 and 80 mg.28 High doses of all statins are associated with higher incidences of myopathy.24,29
When assessing muscle symptoms in people on statins:
- rule out other causes (e.g. increased physical activity, trauma, infections)
- check for risk factors (e.g. dose ≥ 40 mg, age ≥ 70 years, interacting drugs)
- check creatinine kinase (CK) levels
- consider reducing the statin dose or switching to a different statin if symptoms are mild
- stop the statin if muscle symptoms are severe or persistent or if CK > 10 times ULN
- stop the statin and try a non-statin alternative if muscle symptoms recur on statin rechallenge.15,27,29
Encourage long-term adherence by patients
Regularly remind patients of the benefits of lifestyle changes and lipid modifying therapy.
Support people to make lifestyle changes
Suggest patients contact the Heart Foundation (or 1300 36 27 87) for advice on diet, to find a walking group and other preventive activities. Arrange referral to an accredited dietitian through the dietitians association or exercise physiologist for people who are overweight or obese, and for those with cardiovascular disease.
Regularly remind people about the benefits of statin therapy
Reinforce the benefits of statin therapy to patients at every opportunity. Simple reminders are one of the most effective ways of encouraging adherence32:
- Ask patients if they know why they are taking the statin and ensure they understand the benefits and side effects.
- Inform patients that statins work by lowering cholesterol, must be taken continuously to be effective, and have a greater protective effect after the first 1 or 2 years of use.9
- Advise about the relatively low risk of side effects in the context of over 20 years’ use and experience with these medicines. Assess any co-existing conditions or medicines that may make side effects more likely.
- Explain that statins provide an added benefit, but do not replace eating a healthy diet or keeping physically active.
Professor Andrew Tonkin, Head of Cardiovascular Research Unit, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne.
Clinical Associate Professor David Sullivan, Department of Biochemistry, Royal Prince Alfred Hospital, Camperdown, Sydney
Dr James Best, General Practitioner, Sydney
A/Prof Nick Buckley, Consultant Clinical Pharmacologist and Toxicologist, University of New South Wales
Jan Donovan, Consumer Representative
Dr John Dowden, Editor, Australian Prescriber
Dr Graham Emblen, General Practitioner, Toowoomba
Deborah Norton, QUM Pharmacist, West Vic DGP
Susan Parker, Pharmacist, Sydney
Dr Jane Robertson, Senior Lecturer, Discipline of Clinical Pharmacology University of Newcastle
Simone Rossi, Managing Editor, Australian Medicines Handbook
Dr Guan Yeo, Clinical Education Consultant and General Practitioner, Berowra
Any correspondence regarding content should be directed to NPS. Declarations of conflicts of interest have been sought from all reviewers. The opinions expressed do not necessarily represent those of the reviewers.
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- National Cholesterol Education Program Expert Panel (US). Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III Final Report) National Heart, Lung and Blood Institute, National Institutes of Health, 2002. (accessed 3 September 2010).
- Sheridan SL, Viera AJ, Krantz MJ, et al. The effect of giving global coronary risk information to adults: a systematic review. Arch Intern Med 2010;170:230-9.
- Cooper A, Nherera L, Calvert N, et al. Clinical Guidelines and Evidence Review for Lipid Modification: cardiovascular risk assessment and the primary and secondary prevention of cardiovascular disease (revised March 2010). London: National Collaborating Centre for Primary Care and Royal College of General Practitioners, 2008. (accessed 12 August 2010).
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- Sheridan SL, Crespo E. Does the routine use of global coronary heart disease risk scores translate into clinical benefits or harms? A systematic review of the literature. BMC Health Serv Res 2008;8:60.
- New Zealand Guidelines Group. New Zealand Cardiovascular Guidelines Handbook: A summary resource for primary care practitioners. 2nd ed. Wellington: New Zealand Guidelines Group,, 2009. (accessed 2 November 2010).
- Tonkin A, Barter P, Best J, et al. National Heart Foundation of Australia and the Cardiac Society of Australia and New Zealand. Position statement on lipid management 2005. Heart Lung Circ 2005;14:275-91.
- Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005;366:1267-78.
- Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7-22.
- Jackson R, Lawes CM, Bennett DA, et al. Treatment with drugs to lower blood pressure and blood cholesterol based on an individual's absolute cardiovascular risk. Lancet 2005;365:434-41.
- Cardiovascular Writing Group. Therapeutic Guidelines: Cardiovascular. Version 5 ed. Melbourne: Therapeutic Guidelines Ltd, 2008.
- Anderson KM, Odell PM, Wilson PW, Kannel WB. Cardiovascular disease risk profiles. Am Heart J 1991;121:293-8.
- Chow CK, Jolly S, Rao-Melacini P, Fox KA, Anand SS, Yusuf S. Association of diet, exercise, and smoking modification with risk of early cardiovascular events after acute coronary syndromes. Circulation 2010;121:750-8.
- Rossi S, ed. Australian Medicines Handbook. Adelaide, 2010.
- Kearney PM, Blackwell L, Collins R, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet 2008;371:117-25.
- National Heart Foundation of Australia & The Cardiac Society of Australian and New Zealand. Lipid management guidelines--2001. National Heart Foundation of Australia, The Cardiac Society of Australia and New Zealand. Med J Aust 2001;175 Suppl:S57-85.
- Josan K, Majumdar SR, McAlister FA. The efficacy and safety of intensive statin therapy: a meta-analysis of randomized trials. CMAJ 2008;178:576-84.
- Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010;376:1670-81.
- US Food and Drug Administration. FDA Drug Safety Communication: Ongoing safety review of high-dose Zocor (simvastatin) and increased risk of muscle injury. US Food and Drug Administration, 2010. (accessed 12 August 2010).
- Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004;364:685-96.
- Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med 1995;333:1301-7.
- Brugts JJ, Yetgin T, Hoeks SE, et al. The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials. BMJ 2009;338:b2376.
- AstraZeneca Pty Ltd. Crestor Product Information (last updated 3 April 2009).
- Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008;359:2195-207.
- National Prescribing Centre (UK). Ezetimibe/simvastatin may reduce CV events in CKD: but is it better than simvastatin alone? NPC, 2010. (accessed 3 December 2010).
- McKenney JM, Davidson MH, Jacobson TA, et al. Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force. Am J Cardiol 2006;97:89C-94C.
- Merck Sharp & Dohme (Australia) Pty Ltd. Zocor Product Information (last updated September 2010).
- Adverse Drug Reaction Advisory Commitee. Australian Adverse Drug Reaction Bulletin. Risk factors for myopathy and rhabdomyolysis with the statins. Canberra, 2004. (accessed 8 September 2010).
- Lifescripts practice manual: supporting lifestyle risk factor management in general practice. Canberra: Commonwealth of Australia, 2010. (accessed 19 October 2010).
- The Royal Australian College of General Practitioners ‘Green Book’ Project Advisory Committee. Putting prevention into practice: Guidelines for the implementation of prevention in the general practice setting, 2nd edn. South Melbourne: The Royal Australian College of General Practitioners, 2006. (accessed 19 October 2010).
- Schedlbauer A, Davies P, Fahey T. Interventions to improve adherence to lipid lowering medication. Cochrane Database Syst Rev 2008;3:CD004371.