Heart and stroke risk: a catalyst for conversation

INSIDE Determining absolute CVD risk Which patients need assessment Treatment step by step CVD risk guides treatment Keeping you informed on quality use of medicines and medical tests FEBRUARY 2014 MEDICINEWISE NEWS Heart and stroke risk: a catalyst for conversation Appropriate patient selection is key to the effective use of statins for reducing CVD risk. KEY POINTS Various media reports have linked statins to a variety of adverse events and questioned their efficacy, but these drugs remain one of the most effective strategies for reducing the risk of cardiovascular disease (CVD). Recently both Therapeutic Guidelines and the National Vascular Disease Prevention Alliance updated their recommendations on management of absolute CVD risk. Guidelines recommend basing lipid (and other risk factor) management on absolute CVD risk. However, more than 10 years on since the introduction of these recommendations statin prescribing does not always reflect a patient's need based on absolute CVD risk. Find out who needs a risk calculation before treatment and what the assessment and treatment recommendations in Australia are. Statins an effective drug strategy for reducing CVD risk Statin treatment in patients under age 75 should be based on their absolute CVD risk.1 Cardiovascular disease (CVD) is largely preventable but still the most common cause of death in Australia and was responsible for more than one-third of deaths in 2008.2 High plasma cholesterol is an established modifiable risk factor for CVD, and lowering levels of LDL cholesterol plays an important role in preventing cardiovascular events.2 Statins are the most effective lipid-modifying drugs and are the first-line treatment for LDL-cholesterol lowering.2 Statins reduce the risk of cardiovascular events and death for people at elevated CVD risk, regardless of their initial lipid levels.3,4 The benefit of a statin is greatest for those at greatest absolute risk of a cardiovascular event, including those with established CVD.3,4 With conflicting evidence about the benefits and harms of statins5-7 and recent national and international safety updates8-10 it is important that statins are used in the people for whom the benefits are most likely to outweigh the potential harms. Here we review current guidelines to highlight who needs statin treatment and how to identify them. Treat with lipid-lowering drugs in line with absolute CVD risk Guidelines recommend that absolute CVD assessment should provide the basis of CVD risk assessment and treatment.1 Assessment of CVD risk on the basis of the combined effect of multiple risk factors reflects a person's overall risk of CVD and is more accurate than assessment of individual risk factors.1 This forms the basis of an absolute CVD risk assessment. Absolute CVD risk is defined as the probability (as a percentage) of a person having a cardiovascular event over a pre-defined period in the case of Australian guidelines within a 5-year period.2 Guidelines have recommended absolute CVD risk as the basis for lipid management for more than 10 years.11,12 However, treatment with lipidmodifying drugs such as statins often doesn't reflect the person's absolute CVD risk.13-16 This can lead to undertreatment of eligible people and the inappropriate treatment of others.13-16 RESOURCES & ACTIVITIES ON CARDIOVASCULAR RISK M EDICINEWISE NEWS CLINICAL e-audit PHARMACY PRACTICE REVIEW Download a QR reader to your mobile device and scan this QR code to view our patient resources on heart disease and cholesterol. Also available at www.nps.org.au/heart-stroke-cholesterol

Determining absolute CVD risk who needs assessing and how? People in certain risk categories (Box 1) do not need an absolute CVD risk assessment, as they are known to be at high risk of a cardiovascular event. People at high CVD risk require simultaneous treatment with lipid-modifying and BP-lowering medication (unless contraindicated or clinically inappropriate) in addition to lifestyle advice, but they do not require risk calculation. 1 For all other patients aged 45 74 ( 35 for Aboriginal and Torres Strait Islander peoples), use a risk tool to estimate absolute CVD risk accurately. 1,2 The risk tool should be one that is validated in the target patient population. 1 Risk assessment tools For the Australian population Therapeutic Guidelines recommends using the National Vascular Disease Prevention Alliance (NVDPA) absolute cardiovascular disease risk charts 18 or associated web-based calculator (available at www.cvdcheck.org.au ). 19 These were developed using the Framingham Risk Equation, 20 which takes into account: sex age BP smoking status total and HDL-cholesterol (or their ratio) diabetes status left ventricular hypertrophy on ECG (if known). Risk is categorised according to probability of a cardiovascular event in the next 5 years: high (> 15%), moderate (10% to 15%) or low (< 10%). 1,2 Keep up to date Keep up to date with the latest evidence and professional development activities. Sign up to NPS Direct, GP Update or Pharmacist Update at nps.org.au/hporders BOX 1 Assessing and managing risk in people aged over 74 Age is probably the most significant risk factor for CVD. 2 However, on its own it is neither a reason to start nor to contraindicate drug 2 Base the decision to start treatment in these people on clinical judgement taking into account: 2 likely benefits and risks of treatment life expectancy Who doesn't need a risk assessment? 1,2 People for whom high CVD risk can be assumed do not need an absolute CVD risk assessment using the Framingham Risk Equation. This includes people with: Established CVD Diabetes and aged > 60 years Diabetes with microalbuminuria (albumin excretion > 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 proteinurea or egfr < 45 ml/min/1.73 m 2 ) 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 over 74 years * People with serum total cholesterol > 7.5 mmol/l are included on the assumption that this is due to increased levels of LDL-cholesterol (eg, > 5.5 mmol/l) or non-hdl cholesterol (eg, > approximately 6.5 mmol/l). comorbidities and quality of life the patient's personal values. New guidelines for the management of absolute CVD risk developed by the NVDPA were published in 2012, coinciding with the most recent update to Therapeutic Guidelines. 1,2 In a change to previous guidance, 21 the Framingham Risk Equation can now be used to estimate minimum absolute CVD risk in patients aged over 74 who do not have CVD and are not in one of the high-risk categories listed in Box 1. 1,2 The tool has not been validated in these patients, but the estimate may be used to guide management and may help discriminate between patients at moderate and high absolute risk. 2 When using the web calculator tool, to avoid inflating the calculated absolute risk for people aged > 74 their age should be entered as 74, regardless of actual age. 1,2 Professional development opportunities Clinical e-audit for GPs: CVD risk Identify patients who will benefit most from lipid-modifying drugs such as statins. To register go to nps.org.au/clinical-audits Account for other risk factors Risk tools can help guide management but do not replace a full CVD assessment, as it is important to also take into account various risk factors that are not addressed in the Framingham Risk Equation. 1 A comprehensive assessment includes consideration of modifiable risk factors, non-modifiable risk factors and related conditions (see Box 2). 1,2 The assessment should check for groups in which the tool can underestimate risk, for example: Aboriginal and Torres Strait Islander peoples certain ethnic groups people with diabetes (aged 45 60) overweight or obese people people of low socioeconomic status. When these additional factors are present, treat the risk calculated by the tool as a minimum estimate and adjust it using clinical judgement. 2 This is especially important for people determined to be at moderate risk by the tool and who may be considered to need drug treatment based on their additional risk factors. 1 Pharmacy Practice Review for pharmacists: Reducing CVD risk Engage in discussion with patients using statins and/or ezetimibe about reducing their CVD risk. To register go to nps.org.au/ pharmacy-practice-review MEDICINEWISE NEWS FEBRUARY 2014

BOX 2 Risk factors for cardiovascular disease 1 Modifiable risk factors Smoking* Elevated BP* Diabetes* Dyslipidaemia* Central obesity, waist circumference and BMI Poor nutrition Sedentary lifestyle Excessive alcohol intake Non-modifiable risk factors Age* Sex* Family history of premature CVD Social history, including cultural identity and ethnicity (e.g. Aboriginal and Torres Strait Islander, South Asian, Maori and Pacific Islander, Middle Eastern peoples), and lower socioeconomic status Related conditions Left ventricular hypertrophy as diagnosed by ECG* Chronic kidney disease (albuminuria ± urine protein, egfr) 2 Familial hypercholesterolaemia Evidence of atrial fibrillation (history, examination, ECG) 2 Mental health (e.g. depression) * These risk factors are included in the absolute risk calculator, based on the Framingham risk equation. Cardiovascular disease occurring in a first-degree relative aged < 60 years. Resources and tools Order or download from nps.org.au/hporders#cvd-risk-pad Managing my heart health at a glance (helps those with or at risk of cardiovascular disease to track their medical and lifestyle factors) Your heart and stroke risk score (explains absolute cardiovascular risk to patients, available in pads of 50) Online at nps.org.au/cvdrisktools Cardiovascular risk calculators Treatment step by step Patients at high CVD risk drug treatment recommended Treat people at high absolute risk of CVD with lipid-lowering and BP-lowering medication concomitantly unless contraindicated or clinically inappropriate. 1,2 Ensure these people also receive frequent and sustained advice and support about diet and physical activity and stopping smoking to facilitate beneficial lifestyle changes alongside pharmacotherapy. 1,2 (See Assessing and managing risk in people aged over 74 [opposite] for additional considerations in this population). See the August 2013 Health News and Evidence article Stop smoking what works for your patients? for further details of helping patients quit smoking (go to nps.org.au/health-news-evidence). Patients at moderate CVD risk drug treatment not routinely recommended Pharmacotherapy, including treatment with statins, is not routinely recommended for people at moderate risk of CVD. Provide these people with appropriate specific advice and support about diet and physical activity as well as appropriate advice, support and drug therapy for stopping smoking. 1 Consider BP-reducing and/or lipid-modifying therapy (in addition to behavioural risk factor advice) for these people if 3 6 months of behavioural risk factor modification does not reduce their absolute CVD risk or if: their BP is persistently > 160/100 mmhg they have a family history of premature CVD they are of a specific population for which Framingham Risk Equation underestimates their risk. 1,2 Discuss the benefits and harms of drug treatment with these patients, as the absolute benefits may be outweighed by the potential harms (e.g. adverse effects, cost). 1 Patients at low CVD 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, 22 and drug treatment is not routinely recommended. 1 Intervening early with lifestyle changes is the priority (see Managing lifestyle factors, overleaf). Give these people brief general advice regarding diet and physical activity along with appropriate advice, support and drug therapy for smoking cessation. 1 Guidelines recommend that BP-lowering therapy is considered alongside lifestyle advice for these people if their BP is persistently > 160/100 mmhg. 1 Re-calling and re-assessing Repeat the risk assessment every 2 years for people at low risk (to coincide with their BP check), every 6 12 months for people at moderate risk and according to clinical context for people at high risk. 2 MEDICINEWISE NEWS FEBRUARY 2014

Managing lifestyle factors Lifestyle changes should be recommended for everyone and discussed during consultations that assess CVD risk. Practice points Lifestyle changes reduce the risk of cardiovascular events by means independent of lipid lowering;23 they can curb the progression of atherosclerosis24,25 and are effective in primary and secondary prevention of CVD.1 Determine absolute CVD risk of Australian patients using the Australian cardiovascular disease risk charts or associated web calculator (at www.cvdcheck.org.au).1 Base the decision to start treatment in people over 74 on clinical judgement. Their absolute CVD risk score can be used to inform management but do not inflate calculated absolute risk because of age > 75 years. The web calculator corrects for this by requiring maximum age entered to be < 75, regardless of actual age.2 In people in risk categories that put them at high risk of a cardiovascular event (see Box 1), treat with statins and BP-lowering medication. These people do not need a risk calculation.1,2 Assess absolute CVD risk in all other patients aged 45 years, or 35 for Aboriginal and Torres Strait Islander peoples, to determine the need for lipid-lowering treatment.1 Assess absolute CVD risk every 2 years for people at low risk, every 6 12 months for people at medium risk, and according to clinical context for people at high risk.2 Explain to patients at high absolute CVD risk that the aims of treatment are to reduce their overall CVD risk and that they will benefit from combined BP- and lipid-lowering medications even if their individual levels of these risk factors are not elevated.1 Highlight the importance of lifestyle changes for all patients.1 Reprinted from Health News and Evidence, September 2013 (reviewed by Assoc Prof David Sullivan, Royal Prince Alfred Hospital Sydney). For more, visit www.nps.org.au/health-news-evidence 1. etg complete [online]. Therapeutic guidelines: cardiovascular. Melbourne: Therapeutic Guidelines Ltd 2012. http://etg.hcn.com.au/desktop/index.htm (accessed 16 May 2013). 2. National Vascular Disease Prevention Alliance. Guidelines for the management of absolute cardiovascular disease risk. 2012. http://strokefoundation.com.au/site/ media/absolutecvd_gl_webready.pdf (accessed 19 August 2013). 3. Baigent C, et al. Lancet 2005;366:1267 78. 4. Heart Protection Study Collaborative Group. Lancet 2002;360:7 22. 5. Undela K, et al. Breast Cancer Res Treat 2012;135:261 9. 6. McDougall JA, et al. Cancer Epidemiol Biomarkers Prev 2013;22:1529 37. 7. Dormuth CR, et al. BMJ 2013;346:f880. 8. Australian Government Department of Health, Therapeutic Goods Administration. Simvastatin: new contraindications, precautions and dosage recommendations. 2011. http://www.tga.gov.au/ safety/alerts-medicine-simvastatin-111206.htm (accessed 16 April 2013). 9. Australian Government Department of Health, Therapeutic Goods Administration. Statins. 2012. http://www.tga.gov.au/safety/alerts-medicinesstatins-120302.htm (accessed 19 April 2013). www.nps.org.au 10. US Food and Drug Administration. FDA drug safety communication: important safety label changes to cholesterol-lowering statin drugs. 2012. http://www.fda.gov/drugs/drugsafety/ucm293101. htm (accessed 19 April 2013). 11. National Heart Foundation of Australia, The Cardiac Society of Australian and New Zealand. Med J Aust 2001;175[suppl]:S57 85. 12. Tonkin A, et al. National Heart Foundation of Australia, Cardiac Society of Australia and New Zealand. Heart Lung Circ 2005;14:275 91. 13. Wu J, et al. PLoS One 2013;8:e67611. 14. Heeley EL, et al. Med J Aust 2010;192:254 9. 15. Peiris DP, et al. Med J Aust 2009;191:304 9. 16. Webster RJ, et al. Med J Aust 2009;191:324 9. 17. Central Australian Rural Practitioners Association (CARPA). CARPA standard treatment manual, 5th edn. Alice Springs: Central Australian Rural Practitioners Association Inc, 2009. 19. National Vascular Disease Prevention Alliance. Australian absolute cardiovascular disease risk calculator. 2012. http://www.cvdcheck.org.au/ #cvd%20check (accessed 5 September 2013). 20. Anderson KM, et al. Am Heart J 1991;121:293 8. 21. National Vascular Disease Prevention Alliance. Guidelines for the assessment of absolute cardiovascular disease risk. 2009. 22. Ward S, et al. Health Technol Assess 2007;11:1 160,iii iv. 23. Grundy SM, et al. Circulation 2004;110:227 39. 24. 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. http://www.nhlbi.nih.gov/guidelines/cholesterol/ atp3_rpt.htm (accessed 3 September 2010). 25. Ornish D, et al. JAMA 1998;280:2001 7. 18. National Heart Foundation of Australia (National Blood Pressure and Vascular Disease Advisory Committee). Guide to management of hypertension 2008. Updated December 2010. http://www.heartfoundation.org.au/sitecollection Documents/HypertensionGuidelines 2008to2010 Update.pdf (accessed 4 September 2013). Level 7/418A Elizabeth Street Surry Hills NSW 2010 PO Box 1147 Strawberry Hills NSW 2012 02 8217 8700 02 92 1 1 7578 info@nps.org.au Independent, not-for-profit and evidence based, NPS MedicineWise enables better decisions about medicines and medical tests. We are funded by the Australian Government Department of Health. National Prescribing Service Limited. ABN 61 082 034 393. 2014 National Prescribing Service Ltd. The information provided is not medical advice. If you are a health professional, do not solely use the information to treat or diagnose another person's medical condition. If you are not a health professional, do not use it solely to treat or diagnose your own medical condition and never ignore medical advice or delay seeking it because of something herein. Health professionals should rely on their own expertise and enquiries when providing medical advice or treatment. Medicines information changes and may not be accurate when you access it. To the fullest extent permitted by law, National Prescribing Service Ltd (NPS MedicineWise) disclaims all liability (including without limitation for negligence) for any loss, damage, or injury resulting from reliance on, or use of this information. Any references to brands should not be taken as an endorsement by NPS MedicineWise. Our full disclaimer is at http://www.nps.org.au/about-this-website/terms-of-use NPS1465 REFERENCES If you wish to stay up to date with the latest health news and evidence about medicines, medical devices and current health topics join the community of health professionals who subscribe to the monthly e-newsletter NPS Direct. Subscribe at www.nps.org.au/hporders#npsdirect

Fact Sheet Statins frequently asked questions Cardiovascular disease is largely preventable yet continues to be the leading cause of death in Australia. High cholesterol is an established modifiable risk factor, and lowering levels of cholesterol has an important role in preventing cardiovascular events (such as heart attack and stroke). Who should take a statin? In Australia, people are generally prescribed a statin based on their likelihood of having a cardiovascular event, like a heart attack or stroke. The higher your cardiovascular risk, the more likely you will be offered a statin. In some cases this can mean taking a statin even when your cholesterol levels are normal. Clinical trials, such as the Heart Protection Study (involving over 20,000 people), have shown that statins reduce the chance of cardiovascular events in people at high risk whether their blood cholesterol level is high or low. If you have had a heart attack or ischaemic stroke, your risk of having another cardiovascular event is especially high so a statin is generally recommended to lower that risk. Evidence from a large review of clinical trials in people at high risk has shown that statin medicines can substantially lower the chance of having a major cardiovascular event on average by around 20%. This means that if you have been told by your doctor you have a 1 in 5 chance of experiencing a cardiovascular event in the next 5 years, then taking a statin could reduce this to around a 1 in 7 chance. How safe are statins? All medicines (prescription and non-prescription) can have side effects. The chance of developing side effects can vary greatly between people. If a statin has been prescribed or recommended it is important that you discuss possible side effects with your doctor or pharmacist. For most people who are at high risk of heart attack or stroke, the clinical evidence shows that the benefits of lowering cardiovascular risk with a statin medicine outweigh the risk of possible side effects. Not everyone experiences side effects, even when taking the same medicine at the same dose. All prescription medicines, including statins, must also show evidence of safety and effectiveness in humans before they can be sold in Australia. The Therapeutic Goods Administration (TGA) is responsible for looking at all the available scientific and clinical information before approving a medicine for use. Most statin side effects are mild and temporary. A recent review that looked at 135 different studies including safety data from almost 250,000 people found that statins were well tolerated by most people and had few side effects. A slight increase in diabetes (see Do statins cause diabetes?) and abnormal liver enzyme levels was identified. If you think you are experiencing side effects with your statin or other medicine, speak with your doctor or pharmacist. In some cases your doctor may need to reduce the dose, stop statin treatment or change you to a different statin. Do not stop taking your medicine unless advised to by your doctor. You can also call NPS Medicines Line on 1300 MEDICINE (1300 633 424) for information about your prescription, over-the-counter and complementary medicines (natural, herbal, vitamins and minerals) from anywhere in Australia, Monday to Friday, 9am to 5pm AEST (excluding NSW public holidays), for the cost of a local phone call (calls from mobiles may cost more). It is important for you and your doctor to discuss your cardiovascular risk and how beneficial a statin may be for you. Taking any medicine has benefits and risks. Fact Sheet Reduce risk by lowering cholesterol

Can statins cause muscle damage? Muscle pain or weakness are known side effects of statins. They tend to occur more often in people taking higher doses, but others may also be at greater risk, including older people. Mild muscle pain (myalgia) is most common and occurs in 5-15% of people taking a statin. More serious muscle-related side effects like muscle inflammation (myositis) and muscle breakdown (rhabdomyolysis ) occur very rarely. Statins may not be the only reason your muscles feel sore, so discuss any muscle pain or weakness with your doctor so they can investigate the cause. You ll find more information about muscle-related side effects in the consumer medicine information (CMI) for your statin. Will I have memory loss if I take a statin? Memory loss has been reported as a possible statin side effect. However, the number of cases is low and for most people the symptoms reversed when the statin was stopped. Recent reviews of available data have looked closely at this possible side effect and conclude that it is rare. The Therapeutic Goods Administration (TGA) is aware of these reports and is monitoring the situation in Australia. The TGA currently advises people not to stop taking their statin if they experience memory loss, but to talk to their doctor or other health professional. Do statins cause diabetes? A slight increased risk of diabetes has been identified in studies of statins. In a recent review of trials involving over 91,000 people, there was a higher incidence of type 2 diabetes diagnosed among people taking a statin compared with people who were not taking a statin. The increased risk was very small one extra case of diabetes for every 255 people treated with a statin over 4 years. The review also showed that the benefits of taking a statin to lower cardiovascular risk greatly outweighed the possible risk of developing diabetes. Talk to your doctor if you are taking a statin and are concerned about developing diabetes. Your doctor can discuss the benefits and risks of your medicines with you. What is the strong evidence I keep hearing about statins? Evidence for statins has come from many different clinical trials over 30 years. In fact, the complexity of the clinical research is one of the reasons for the current debate about the role of statins. Trials of statins have been conducted in a wide range of groups, including older and younger people, people at high or low cardiovascular risk, and people with or without diabetes. These differences can make it harder to interpret the evidence about statins, especially if they find diverse or conflicting results. In recent years, evidence from statin trials has been carefully analysed by a number of research organisations including the Cochrane Collaboration, the Cholesterol Treatment Trialists Collaboration and the PROSPERO group. These organisations have conducted large reviews of the evidence for statins by pulling together the results from different trials (a method called meta-analysis ). Gathering evidence in this way is scientifically valid and can help to improve our understanding of the impact statins have on cardiovascular risk in many different situations. Overall, these large reviews agree that statins can reduce the chance of heart attack or stroke for people at high risk, regardless of whether they: have had a cardiovascular event before or not have a high or normal blood cholesterol level. In 2012 the National Vascular Disease Prevention Alliance (NVDPA) released Australian guidelines on managing cardiovascular disease for people at risk. These are based on the latest evidence to enable everyone to receive the best treatment. Are statins the only way to manage cardiovascular risk? Statins are an important treatment for many people to help them manage their cardiovascular risk. Dietary and lifestyle changes are also essential to lower your cardiovascular risk. Current guidelines recommend the following: stop smoking eat a healthy diet that includes plenty of fruits, vegetables, wholegrain cereals, lean meat, poultry, fish, eggs, nuts and seeds, legumes and beans, and low-fat dairy products limit saturated and trans fats (also known as hydrogenated or partially hydrogenated fats, and mostly found in processed foods like baked or deep fried goods) limit salt and alcohol be physically active for at least 30 minutes most days maintain a healthy weight. If you are at high risk of cardiovascular problems, diet and lifestyle alone will not be enough to lower your risk. Your doctor will discuss the need for statins and other medicines (like blood pressuring-lowering medicines) to reduce your cardiovascular risk. This is also the case for some people at moderate risk, who are unable to lower their risk with diet and lifestyle alone. For the answers to more questions about statins go to nps.org.au/statins-faq Published February 2014. Level 7/418A Elizabeth St Surry Hills NSW 2010 PO Box 1147 Strawberry Hills NSW 2012 02 8217 8700 02 9211 7578 info@nps.org.au www.nps.org.au Independent, not-for-profit and evidence based, NPS MedicineWise enables better decisions about medicines and medical tests. We are funded by the Australian Government Department of Health. National Prescribing Service Limited. ABN 61 082 034 393. 2014 National Prescribing Service Ltd. The information provided is not medical advice. Do not use it to treat or diagnose your own or another person s medical condition and never ignore medical advice or delay seeking it because of something herein. Medicines information changes and may not be accurate when you access it. To the fullest extent permitted by law, National Prescribing Service Ltd (NPS MedicineWise) disclaims all liability (including without limitation for negligence) for any loss, damage, or injury resulting from reliance on, or use of this information. Any references to brands should not be taken as an endorsement by NPS MedicineWise. Our full disclaimer is at http://www.nps.org.au/about-this-website/terms-of-use Fact Sheet Reduce risk by lowering cholesterol NPS1466