Managing lipids - reducing cardiovascular disease risk

Published in MedicineWise News

Date published: About this date

Clinical content may change after this date. This information is not intended as a substitute for medical advice from a qualified health professional. Health professionals should rely on their own expertise and enquiries when providing medical advice or treatment.

It is 10 years since guidelines first recommended absolute cardiovascular risk as the basis for lipids management.1,2 However, many Australians who could benefit from a lipid-modifying drug are not being treated, because their risk has been underestimated or has not been assessed at all.3-5 This News outlines tools for identifying people at increased cardiovascular risk and strategies to help people stay on effective treatment.

Assess absolute cardiovascular risk routinely

Absolute cardiovascular risk assessment is an essential part of lipid management.1,6 It helps to determine who may benefit from lipid management and also helps to:

  • target drug therapy to those at greatest risk7
  • motivate people to reduce their risk8
  • prioritise lipids management alongside that of other risk factors.9

Checking lipid levels remains important — to screen for dyslipidaemias from secondary causes10, to identify extreme levels where high cardiovascular risk can be assumed (e.g. total cholesterol > 7.5 mmol/L)9,11 and to check if a person qualifies for PBS subsidy of a lipid-lowering drug.12

Use risk tools when assessing people without cardiovascular disease

People with existing cardiovascular disease or with certain risk factors (Box 1) are known to be at increased risk and so do not require screening with a tool. For everyone else aged 45–74 years (≥ 35 years for Aboriginal and Torres Strait Islander peoplesA), use a risk tool to estimate absolute cardiovascular risk accurately.1,9

Australian guidelines recommend the Australian cardiovascular risk charts or associated web calculatorB.9 These were developed using the Framingham Risk Equation — accounting for sex, age, blood pressure, smoking status, total and HDL cholesterolC (or their ratio), diabetes status, and left ventricular hypertrophy (LVH) on ECG (if known).13 Risk is categorised according to probability of a cardiovascular event in the next 5 years: high (> 15%), moderate (10% to 15%) or low (< 10%).9

A. Central Australian Rural Practitioners Association (CARPA) Standard Treatment Manual (2009) recommends cardiovascular risk assessment for all Aboriginal and Torres Strait Islander peoples ≥ 20 years.
B. These replace the New Zealand Cardiovascular Risk Calculator.
C. High-density-lipoprotein cholesterol.

Repeat the risk assessment every 2 years for people at low risk (to coincide with their blood pressure check), every 6–12 months for people at moderate risk and according to clinical context for people at high risk.9

Account for other risk factors

Risk tools can help guide management, but do not replace a full cardiovascular assessment.9,14 Assess all risk factors including those not accounted for by the tool: family history of cardiovascular disease, body mass index or waist circumference, nutrition, physical activity, alcohol intake and mental health.1,9 Check for groups where the tool can underestimate risk: Aboriginal and Torres Strait Islander peoples, certain ethnic groups, and people with diabetes (aged 45–60 years), atrial fibrillation, high body mass index, or low socioeconomic status.9,15 Where these additional factors are present, treat the risk calculated by the tool as a minimum estimate and adjust it using clinical judgment.6,9

Risk tools are not applicable to people aged > 74 years, so assess risk clinically for this group.9 Risk tools have not been validated for improvements to cardiovascular outcomes.16

Box 1: Who doesn’t need a risk tool assessment

Anybody for whom high cardiovascular risk can be assumed including people with:

  • any cardiovascular disease
  • diabetes mellitus aged > 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
  • total serum cholesterol > 7.5 mmol/L.9

Lifestyle changes are essential for everyone

Always ask about lifestyle factors when assessing cardiovascular risk (see Motivating people to manage their risk). Lifestyle changes reduce the risk of cardiovascular events by means independent of lipid lowering17, they can curb progression of atherosclerosis18,19, and are effective in primary and secondary cardiovascular prevention.20

How effective are lifestyle changes?

Smoking cessation markedly reduces cardiovascular risk, improves survival and should be a management priority.10 People who quit at 30, 40, 50 or 60 years can gain an extra 10, 9, 6 and 3 years of life expectancy, respectively.21 The benefits of quitting far outweigh any disadvantages, such as weight gain.10

Regular physical activity reduces cardiovascular risk in healthy people22,23, improves survival after myocardial infarction24 and favourably affects lipids as well as other risk factors.6

Walking briskly or exercising vigorously for 2.5–3.5 hours a week lowers the relative risk of a first cardiovascular event by around 18% to 30%, according to observational studies.22,23 People who are physically active after a coronary event have up to 27% lower relative risk of death for up to 5 years of follow-up, compared with people who are inactive.25

Modifying dietary fat can reduce LDL cholesterolD by up to 16%.26 Over 6 months, such dietary advice can reduce the relative risk of cardiovascular events by 16%, with a greater risk reduction over 2 years.27 However, modifying dietary fat alone should not be relied upon in primary prevention; a large trial of postmenopausal women found it ineffective in reducing cardiovascular event rates.28

The Mediterranean dietE over 4 years, while not affecting LDL cholesterol, reduced the relative risk of cardiac death and nonfatal myocardial infarction by 72% compared with a Western-type prudent diet in a trial of myocardial infarction (MI) survivors.29 Data from cohort studies suggests that greater adherence to this diet in primary prevention populations had a 9% relative reduction in the risk of death.30

Plant sterol esters at a dose of about 2 g a day from a fortified food (e.g. margarine) reduce LDL cholesterol by about 10%, or by a further 7% to 16% when added to statin therapy. However, no trials have assessed whether plant sterol esters reduce cardiovascular risk.6,31

Fish oil (omega-3 fatty acid) supplements reduce triglycerides (by 20% to 30%), increase HDL cholesterol (by 1% to 3%) and are recommended for treating hypertriglyceridaemia.10,32 Despite numerous trials, it is unclear if fish oil supplements reduce the rate of cardiovascular events in people at increased cardiovascular risk.33-35 There is not enough information to rule out a small benefit in people with heart failure34 and MI survivors.36 Based on population studies, guidelines recommend consuming fish (fresh or canned) 2 or 3 times a week as part of an overall healthy eating plan.1,10,32

D. Low-density-lipoprotein cholesterol.
E. High in wholegrain breads and cereals, fruit and vegetables, olive oil and fish.

Manage lipids according to cardiovascular risk

Use absolute cardiovascular risk to guide choice and intensity of management; people at greatest risk derive the greatest benefit from intensive treatment.6,11

Low cardiovascular risk — focus on lifestyle

The costs and, to a lesser extent, the potential harms of lipid-modifying drugs probably exceed the benefits for people at low risk.37 Intervening early with lifestyle changes is the priority: once a person has advanced atherosclerosis, drug therapies can reduce risk, but not to the level of a person with minimal coronary lesions.18

Moderate or greater cardiovascular risk — consider for drug treatment

Guidelines recommend a lipid-modifying drug together with lifestyle changes for everyone who is already known to be at high cardiovascular risk (Box 1).1

A lipid-modifying drug together with lifestyle changes is also recommended for people who have:

  • diabetes and who are an Aboriginal or Torres Strait Islander
  • a strong family history of very early coronary heart disease
  • a high cardiovascular risk (≥ 15% in the next 5 years)
  • a moderate cardiovascular risk (10% to 15% in the next 5 years) and who have metabolic syndrome or a family history of early coronary heart disease.1,12

Recognise that for some high risk conditions (e.g. familial hypercholesterolaemia) lipid checks are required before and after a dietary trial for subsidy under the Pharmaceutical Benefits Scheme (PBS). Also, some people identified as high risk by risk tool assessment or by guidelines may not qualify for PBS subsidy5,38; chronic kidney disease, atrial fibrillation and smoking status are not PBS criteria.

Statins are the drugs of choice

Statins reduce the risk of cardiovascular events and death for people at elevated cardiovascular risk, regardless of their initial lipid levels.39,40 Although effective for people with established disease and for those otherwise at increased cardiovascular risk, the benefit of a statin is greatest for those at greatest risk of a cardiovascular event.39,40

About 12 people with established disease need to be treated with a statin instead of placebo for 5.4 years to prevent one major coronary event.41 About 77 people at elevated cardiovascular risk without established disease need to be treated with a statin instead of placebo for 4.1 years to prevent one
major coronary event.42

Statins differ in potency but none has a proven advantage

Evidence suggests that the efficacy of statins in reducing cardiovascular risk depends on the extent of LDL cholesterol lowering rather than the specific drug used.10,43 Pooled trial results show a 1% lowering of LDL cholesterol is associated with a 1% relative risk reduction of major coronary events.11 On this basis, a relatively greater reduction in cardiovascular risk might be expected from a drug regimen that causes a greater lowering of LDL cholesterol, regardless of the statin used.

However, choice of a drug regimen should take into account the absolute risk of the patient. Although some statin regimens achieve greater reductions in LDL cholesterol than others44 (Figure 1), intensive statin therapy may not be appropriate for everyone at increased cardiovascular risk. High doses of all statins are associated with an increased risk of myopathy45,46, and while trials have shown that more intensive cholesterol lowering is beneficial for people with cardiovascular disease47 this has not been confirmed for people without established disease. Recognise that more than 80% of the LDL-lowering effect of any statin is achieved with 50% of its maximum dose (see Figure 1).32

Statin effect on LDL

Figure 1: Statin effect on LDL cholesterol44
Derived from a meta-analysis of short-term trials. Height of bar indicates the point estimate for the dose.

Other lipid-modifying drugs have a limited role

Nicotinic acid, bile-acid resins, ezetimibe and fibrates (fenofibrate, gemfibrozil) are alternatives for people who cannot tolerate a statin, and may be used as adjuvant therapy for those who require, but cannot tolerate, a high-dose statin.6,10 None of these agents lowers LDL cholesterol as effectively as a statin and not all have been shown to improve cardiovascular outcomes.48 Nicotinic acid, cholestyramine and gemfibrozil have been shown to reduce rates of major coronary events compared with placebo for people at increased cardiovascular risk.32 However, use of nicotinic acid or cholestyramine is limited by adverse effects and gemfibrozil’s benefit appears limited to those with abnormal triglyceride and HDL cholesterol levels — as it has a modest effect on LDL cholesterol levels.32,49 Combination therapy with a statin can reduce LDL cholesterol by an additional 10% to 15% for bile resins, and up to 20% for ezetimibe and nicotinic acid.11,50 However, no additional reduction in cardiovascular risk from combination therapy has been shown.50

Consider concomitant medicines, co-existing conditions, and patient preferences when selecting one of these drugs. Avoid combining gemfibrozil or nicotinic acid with a statin, as these combinations can increase the risk of myopathy.10

Selecting a statin and determining dose

Treat intensively in secondary prevention

Start people with stable cardiovascular disease on a statin dose with a moderate LDL-lowering effect (e.g. simvastatin 40 mg or atorvastatin 10 mg), then treat to a target LDL cholesterol < 2 mmol/L.1,6 Consider a statin dose with a greater LDL-lowering effect for people with acute coronary syndrome (atorvastatin 80 mg or simvastatin 80 mg were used in trialsG).6

Intensive lowering of LDL cholesterol is beneficial in secondary prevention, even if the target LDL cholesterol cannot be achieved.1,6,51 High doses of statins (e.g. atorvastatin 80 mg) reduce the relative risk of major cardiovascular events by a further 15% compared with moderate doses (e.g. pravastatin 40 mg) for people with cardiovascular disease.47 However, high statin doses are associated with higher incidences of myopathy (0.03% versus 0.9% with simvastatin 20 mg versus 80 mg)52 and elevated liver enzymes (0.4% versus 1.5% with less intensive versus more intensive regimens).51 Monitor people taking high statin doses closely for muscle effects and for changes to liver enzymes.51

Use absolute risk to inform treatment in primary prevention

Start people without cardiovascular disease who are otherwise at high cardiovascular risk on a statin dose with a moderate LDL-lowering effect.6,11,14 In primary prevention, simvastatin 40 mg, atorvastatin 10 mg, or pravastatin 40 mg reduced the relative risk of major coronary events by 25% to 35%.40,42,53,54 Rosuvastatin 20 mg reduced cardiovascular events in a primary prevention trial, but the long-term safety of this dosing regimen for this population has not been established.55

Treat to a target LDL cholesterol < 2.5 mmol/L in primary prevention1, taking into account the person’s cardiovascular risk score, co-morbidities, life-expectancy and their preferences.6 A lower target LDL cholesterol < 2 mmol/L may be appropriate for some high risk groups, such as people with diabetes.6 No trials have compared moderate LDL-lowering regimens with more intensive regimens in people without cardiovascular disease, so the benefits and safety of intensive statin therapy have not been directly evaluated in this population.6

G. The doses of these drugs do not have an equivalent LDL-lowering effect. See Figure 1.

Motivating people to manage their cardiovascular risk

People who are well informed and involved in decisions about their own care are more likely to adhere to an agreed management plan.6

Discuss absolute cardiovascular risk with people and use risk tools to show how modifying different risk factors can reduce risk. Explaining the meaning of an individual’s risk score can motivate them to make lifestyle changes or start treatment and may encourage adherence.6,8

Regularly remind people to take statins, if prescribed

Persistence rates for statins are low.56 An Australian study found that only 40% of people continued to take their statin at 12 months, with about half stopping before 3 months.57 More often people stopped their statin because they were unconvinced about the benefit or because of lack of efficacy (as assessed by their doctor) rather than for side effects.57

Make statin adherence an ongoing discussion point and let patients know that you will be asking about this at each visit.18,58 Routinely discuss the benefits of statin therapy alongside healthy eating and keeping physically active.58 Inform patients that statins work by lowering cholesterol, must be taken continuously to be effective, and have a greater protective effect after the first 1–2 years of use.39 Ensure that patients understand that the medicine provides an added benefit, but doesn’t replace lifestyle changes.

Provide support for lifestyle changes

A ‘stages of change’ approach (Ask, Assess, Advise, Assist, Arrange) can help people to make and sustain changes to their diet and physical activities, as well as their smoking status (see the RACGP SNAP guide). The Lifescripts program includes self-assessment forms and action plans on nutrition and weight management, and physical activity.

Encourage people to contact the Heart Foundation for tips on how to reduce saturated fat in their diet, and for general information on ‘Healthy eating’ and keeping physically active. Consider referral to an exercise physiologist or a dietician for people at high cardiovascular risk.

Expert reviewers

Prof 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, 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.

  1. 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.
  2. 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.
  3. Webster RJ, Heeley EL, Peiris DP, et al. Gaps in cardiovascular disease risk management in Australian general practice. Med J Aust 2009;191:324–9.
  4. 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.
  5. Peiris DP, Patel AA, Cass A, et al. Cardiovascular disease risk management for Aboriginal and Torres Strait Islander peoples in primary health care settings: findings from the Kanyini Audit. Med J Aust 2009;191:304–9.
  6. 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).
  7. 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.
  8. 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.
  9. National Vascular Disease Prevention Alliance. Guidelines for the assessment of absolute cardiovascular disease risk. 2009. (accessed 12 August 2010).
  10. Cardiovascular Writing Group. Therapeutic Guidelines: Cardiovascular. Version 5 ed. Melbourne: Therapeutic Guidelines Ltd, 2008.
  11. Scottish Intercollegiate Guidelines Network (SIGN). Risk estimation and the prevention of cardiovascular disease. a national clinical guideline, February 2007. Edinburgh: SIGN. (accessed 12 August 2010).
  12. Australian Government Department of Health and Ageing. Schedule of Pharmaceutical Benefits. Canberra: Commonwealth of Australia 2010. (accessed 17 September 2010).
  13. Anderson KM, Odell PM, Wilson PW, et al. Cardiovascular disease risk profiles. Am Heart J 1991;121:293–8.
  14. 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).
  15. National Heart Foundation of Australia. Guide to management of hypertension 2008:  Updated August 2009. Web version. National Heart Foundation, 2009. (accessed 14 September 2010).
  16. Brindle P, Beswick A, Fahey T, et al. Accuracy and impact of risk assessment in the primary prevention of cardiovascular disease: a systematic review. Heart 2006;92:1752–9.
  17. Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004;110:227–39.
  18. 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).
  19. Ornish D, Scherwitz LW, Billings JH, et al. Intensive lifestyle changes for reversal of coronary heart disease. JAMA 1998;280:2001–7.
  20. Joint British Societies. JBS2:  Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice, December 2005. Heart;91.
  21. Doll R, Peto R, Boreham J, et al. Mortality in relation to smoking: 50 years' observations on male British doctors. BMJ 2004;328:1519.
  22. Tanasescu M, Leitzmann MF, Rimm EB, et al. Exercise type and intensity in relation to coronary heart disease in men. JAMA 2002;288:1994–2000.
  23. Manson JE, Greenland P, LaCroix AZ, et al. Walking compared with vigorous exercise for the prevention of cardiovascular events in women. N Engl J Med 2002;347:716–25.
  24. Blumenthal JA, Babyak MA, Carney RM, et al. Exercise, depression, and mortality after myocardial infarction in the ENRICHD trial. Med Sci Sports Exerc 2004;36:746–55.
  25. Jolliffe JA, Rees K, Taylor RS, et al. Exercise-based rehabilitation for coronary heart disease. Cochrane Database Syst Rev 2000:CD001800.
  26. Yu-Poth S, Zhao G, Etherton T, et al. Effects of the National Cholesterol Education Program's Step I and Step II dietary intervention programs on cardiovascular disease risk factors: a meta-analysis. Am J Clin Nutr 1999;69:632–46.
  27. Hooper L, Summerbell CD, Higgins JP, et al. Reduced or modified dietary fat for preventing cardiovascular disease. Cochrane Database Syst Rev 2001:CD002137.
  28. Howard BV, Van Horn L, Hsia J, et al. Low-fat dietary pattern and risk of cardiovascular disease: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 2006;295:655–66.
  29. de Lorgeril M, Salen P, Martin JL, et al. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. Circulation 1999;99:779–85.
  30. Sofi F, Cesari F, Abbate R, et al. Adherence to Mediterranean diet and health status: meta-analysis. BMJ 2008;337:a1344.
  31. National Heart Foundation. Summary of evidence: Phytosterol/Stanol enriched foods (updated December 2009). (accessed 12 November 2010).
  32. Rossi S, ed. Australian Medicines Handbook. Adelaide, 2010.
  33. Hooper L, Thompson RL, Harrison RA, et al. Omega 3 fatty acids for prevention and treatment of cardiovascular disease. Cochrane Database Syst Rev 2004:CD003177.
  34. Rauch B, Schiele R, Schneider S, et al. OMEGA, a Randomized, Placebo-Controlled Trial to Test the Effect of Highly Purified Omega-3 Fatty Acids on Top of Modern Guideline-Adjusted Therapy After Myocardial Infarction. Circulation 2010;22:2152–9.
  35. Kromhout D, Giltay EJ, Geleijnse JM. n-3 Fatty Acids and Cardiovascular Events after Myocardial Infarction. N Engl J Med 2010;363:2015–26.
  36. Tavazzi L, Maggioni AP, Marchioli R, et al. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 2008;372:1223–30.
  37. Ward S, Lloyd Jones M, Pandor A, et al. A systematic review and economic evaluation of statins for the prevention of coronary events. Health Technol Assess 2007;11:1–160, iii–iv.
  38. Chen L, Rogers SL, Colagiuri S, et al. How do the Australian guidelines for lipid-lowering drugs perform in practice? Cardiovascular disease risk in the AusDiab Study, 1999-2000. Med J Aust 2008;189:319–22.
  39. 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.
  40. 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.
  41. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383–9.
  42. 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.
  43. National Institute for Health and Clinical Excellence. Statins for the prevention of cardiovascular events in patients at increased risk of developing cardiovascular disease or those with established cardiovascular disease.  Technology Appraisal 94. London: NICE, 2006. (accessed 13 September 2010).
  44. Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ 2003;326:1423.
  45. 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).
  46. AstraZeneca Pty Ltd. Crestor Product Information (last updated 3 April 2009). 2009; December 2010.
  47. 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.
  48. Rossebo AB, Pedersen TR, Boman K, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med 2008;359:1343–56.
  49. Bruckert E, Labreuche J, Amarenco P. Meta-analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosis. Atherosclerosis 2010;210:353–61.
  50. Genest J, McPherson R, Frohlich J, et al. 2009 Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult – 2009 recommendations. Can J Cardiol 2009;25:567–79.
  51. 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.
  52. Armitage J, Bowman L, Wallendszus K, et al. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. Lancet 2010;376:1658–69.
  53. 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.
  54. 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.
  55. 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.
  56. Benner JS, Glynn RJ, Mogun H, et al. Long-term persistence in use of statin therapy in elderly patients. JAMA 2002;288:455–61.
  57. Simons LA, Levis G, Simons J. Apparent discontinuation rates in patients prescribed lipid-lowering drugs. Med J Aust 1996;164:208–11. 
  58. Schedlbauer A, Davies P, Fahey T. Interventions to improve adherence to lipid lowering medication. Cochrane Database Syst Rev 2008;3:CD004371.