Hyperlipidaemia, dyslipidaemia and hypercholesterolaemia

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1 Medicine > Cardiology > Hyperlipidaemia, dyslipidaemia and Background information Patient information including patient decision aid Key messages for this pathway FH specialist nurse contact details Local formulary information: lipidregulating drugs Dyslipidaemia and cardiovascular risk Established cardiovascular disease Baseline assessment including investigations Patient has diabetes mellitus Go to type 2 diabetes - management No established cardiovascular disease and no familial hypercholesterolaemi a (FH) Formal risk assessment Severe hypertriglyceridemia >10mmol/L Suspected familial hypercholesterolaemi a (FH) Primary care diagnostic criteria for FH after 2 fasting lipid profiles 3 months apart Treat secondary causes of dyslipidaemia Consider seeking specialist advice Estimated 10-year risk 20% or greater Estimated 10-year risk less than 20% - consider other factors Refer to FH Coordinator for consideration of genetic testing Offer statin therapy as soon as possible Patient advice during statin therapy 10-year cardiovascular risk reassessed to be 20% or greater 10-year cardiovascular risk less than 20% Positive genetic screen FH Coordinator will organise cascade testing of family Negative genetic screen Provide lifestyle advice Laboratory monitoring of cholesterol and liver function Consider adverse effects from statins Target for cholesterol during treatment Baseline assessment including investigations Treat secondary causes of dyslipidaemia Consider seeking specialist advice Provide lifestyle advice LDL cholesterol reduced by 50%: continue primary care management Lipid management in primary care LDL cholesterol unable to be reduced by 50%: refer to lipid clinic R Provide lifestyle advice Drug therapy to achieve cholesterol target Offer statin therapy Fasting serum triglycerides persistently >5mmol/L Patient advice during statin therapy Statin intolerance or interactions Monitoring of cholesterol is NOT required Laboratory monitoring monitoring of liver function Consider adverse effects from statins Statin intolerance or interactions Page 1 of 18

2 Medicine > Cardiology > Hyperlipidaemia, dyslipidaemia and 1 Background information Scope: assessment and initial management of dyslipidaemia and familial (FH) in adults lipid modification in primary and secondary prevention of cardiovascular disease (CVD) lifestyle and pharmacological interventions side effect profile of statins Out of scope: detailed management of other risk factors associated with CVD recommended methods for calculating an individual s risk of future cardiovascular events Definition: dyslipidaemia is defined as an abnormality in, or abnormal amounts of, lipids and lipoproteins in the blood dyslipidaemia can be inherited (eg FH) or acquired (due to other conditions, eg diabetes) FH is a genetic condition that causes a high cholesterol concentration in the blood from birth and can lead to early development of atherosclerosis and coronary heart disease (CHD): homozygous FH is diagnosed in people who have inherited a defective gene from both parents heterozygous FH is diagnosed in those who have inherited a defective gene from only one pare risk value is increased by a factor of 1.5 for south asian ethnicity the elevated serum cholesterol concentrations that characterise heterozygous FH lead to a greater than 50% risk of CHD by age 50 years in men and at least 30% in women by age 60 years FH can be caused by a mutation in one of at least three genes patients with FH and their families should be looked after by lipid specialists Incidence and prevalence: CVD is the main cause of death in England and Wales: there are more than three million people living with CVD in 2005, CVD was the cause of one in three deaths heterozygous FH is one of the most common inherited metabolic disorders, with an estimated prevalence in the UK of 1:500 homozygous FH has an incidence of approximately 1:1,000,000 Prognosis: men under age 75 years are three times more likely than women to die from CVD; however, women have a higher case-fatality rate as they are more likely to be under-diagnosed and less likely to be optimally treated three modifiable risk factors smoking, raised blood pressure (BP), and cholesterol account for 80% of all premature coronary heart disease (CHD) FH leads to a greater than 50% risk of CHD by age 50 years in men and at least 30% in women by age 60 years References: National Collaborating Centre for Primary Care (NCCPC). Lipid modification: Cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. Clinical guideline 67. London: NICE; 2008 DeMott K, Nherea L, Shaw EJ et. Clinical guidelines and evidence review for familial : the identification and management of adults and children with familial. London: National Collaborating Centre for Primary Care (NCCPC) and Royal College of General Practitioners (RCGP); 2008 Joint British Societies (JBS). JBS 2: Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice. Heart 2005; 91 Suppl 5: v1-v52 Clinical Knowledge Summaries (CKS). Lipid modification primary and secondary CVD prevention. Version 1.5. Newcastle upon Tyne: CKS; 2008 National Institute for Health and Clinical Excellence (NICE). Statins for the prevention of cardiovascular events. Technology Appraisal 94. London: NICE; 2006 National Institute for Health and Clinical Excellence (NICE). Ezetimibe for the treatment of primary (heterozygous-familial and nonfamilial). Technology appraisal 132. London: NICE; 2007 Abourbih S, Filion KB, Joseph L et al. Effect of fibrates on lipid profiles and cardiovascular outcomes: a systematic review. Am J Med 2009; 122: Page 2 of 18

3 Medicine > Cardiology > Hyperlipidaemia, dyslipidaemia and Jun M, Foote C, Lv J et al. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet 2010; 375: Patient information including patient decision aid Patient decision aid: High Cholesterol - Option Grid 3 Key messages for this pathway This pathway has been locally developed for South West Hampshire. Key messages for this pathway: cardiovascular risk assessment is not required for secondary prevention, or when familial is suspected, since these patients are already at high risk refer for genetic testing when familial is suspected target for treatment in secondary prevention should ideally be total cholesterol <4mmol/L or LDL cholesterol <2mmol/L. However, there is a 'minimum audit standard' and QoF target of Tc 5mmol/L, as it is recognized that more than half the treated population will not achieve the lower targets even with 'high intensity statins'. for primary prevention, there is no target for cholesterol and treatment with simvastatin 40mg is sufficient unless interacting cardiac medication calls for a lower dose. do not routinely measure creatine kinase (CK) during statin treatment. It should only be measured if there are muscle symptoms women with FH should be advised that lipid-modifying drug treatment should not be taken if they are planning to conceive or during pregnancy, due to the potential risk of fetal abnormality. Contributors to this pathway: Dr Emmanuel Abu, UHS Ms Julia Bowey, SCCCG Professor Christopher Byrne, UHS Dr Simon Hunter, WHCCG Ms Maggie Kelly, WHCCG Dr Derek Waller, UHS 4 FH specialist nurse contact details Familial specialist nurse Wessex Genetics Service G Level, Mailpoint 105 Princess Anne Hospital Coxford Road Southampton SO16 5YA Tel: Fax: Page 3 of 18

4 Medicine > Cardiology > Hyperlipidaemia, dyslipidaemia and Secure 5 Local formulary information: lipid-regulating drugs Joint Formulary information 2.12 Lipid-regulating Drugs Statins simvastatin tab - first choice statin pravastatin tab - alternative to simvastatin if potential drug interactions, or simvastatin 40mg is contra-indicated or not tolerated atorvastatin tab rosuvastatin tab - only if intolerant to other statins Bile acid sequestrants colestyramine sach - usually following specialist advice Ezetimibe ezetimibe tab - mainly reserved as an adjunct to statins for patients with primary Fibrates fenofibrate cap - first choice fibrate. Consider only when a statin or other effective treatments are contra-indicated or not tolerated bezafibrate MR tab - usually following specialist advice - consider only when a statin or other effective treatments are contraindicated or not tolerated Lipid lowering advice 6 Dyslipidaemia and cardiovascular risk NICE guidelines recommend: using a systematic strategy to identify people between age 40 and 74 years who are likely to be at high risk of CVD discussing the process of risk assessment with the person identified as being at risk, including the option of declining any formal risk assessment prioritising people: on the basis of an estimate of their cardiovascular disease (CVD) risk before a full formal risk assessment estimate risk using risk factors already recorded in primary care medical records for a full formal risk assessment if their estimated 10-year risk of CVD is 20% or more people with either of the following can be assumed to have a 10-year risk of at least 20% of developing CVD: established CVD familial reviewing on an ongoing basis the estimate of CVD risk in people older than age 40 years opportunistic assessment should not be the main strategy used in primary care to identify CVD risk in unselected people Dyslipidaemia and CVD: lipoproteins are one aspect of cardiovascular risk multiple risk factors contribute to an individual's overall risk of a CVD event risk assessment determines the patient's overall risk of a future CVD event including the risks of stroke and transient ischaemic attack (TIA): the level of one risk factor in isolation is an inadequate guide to overall cardiovascular risk and potential benefit from interventions, although some factors may need to be addressed regardless of total risk for example, high blood pressure treatment of single risk factors in those at low total CVD risk should usually be avoided for the same cholesterol value, some individuals will be eligible for lipid-lowering therapy and others will not, according to total CVD risk management aims to reduce this overall risk by addressing the modifiable risk factors the relationship between blood cholesterol and cardiovascular risk is continuous Page 4 of 18

5 Medicine > Cardiology > Hyperlipidaemia, dyslipidaemia and low-density lipoprotein (LDL) cholesterol is a more accurate predictor of CVD events than total cholesterol, and is the primary target for reducing cardiovascular risk with lipid-modifying treatment the majority of patients with chronic heart disease (CHD) do not have a recognised dyslipidaemia, but all require treatment with LDL-lowering drugs to reduce cardiovascular risk 7 Established cardiovascular disease Patients with established cardiovascular disease (CVD; previous CVD event) can be assumed to be high risk and do not require formal risk assessment. 9 Severe hypertriglyceridemia >10mmol/L Raised serum triglyceride can only be assessed on a fasting blood sample. Severe hypertriglyceridaemia (>10 mmol/l) substantially increases the risk of pancreatitis and specialist advice is recommended. Severe hypertriglyceridaemia is not usually caused by diabetes or obesity. It usually reflects a clearance problem with triglyderiderich lipoproteins from the circulation. Consider requesting Advice and Guidance via Choose and Book as an alternative to an outpatient appointment. 10 Suspected familial (FH) Diagnosis of familial (FH) The diagnostic criteria are for identifying an index case and not for deciding which family members are likely to have FH. Screening of family members is based on plasma LDL concentrations according to age and sex. See NICE CG71 nicemedia/live/12048/41697/41697.pdf Consider a diagnosis of FH in those who have: total cholesterol greater than 7.5mmol/L AND LDL cholesterol greater than 6.0mmol/L or greater than 5.5mmol/L in a young adult AND fasting triglyceride concentrations less than 4.0 mmol/l Values should be obtained pre-treatment, or if not possible, then highest on treatment. Confirm on a second fasting blood specimen, 3 months later. Consider a clinical diagnosis of homozygous FH (inheritance of a defective gene from both parents) in adults with LDL-cholesterol concentration greater than 13.0mmol/L. Exclude secondary causes of before considering a diagnosis of FH. 11 No established cardiovascular disease and no familial (FH) Dyslipidaemia and cardiovascular disease (CVD): risk assessment determines the patient's overall risk of a future CVD event, including the risk of stroke and transient ischaemic attack (TIA) management aims to reduce the overall risk by addressing the modifiable risk factors low-density lipoprotein (LDL) cholesterol is a more accurate predictor of CVD events than total cholesterol, and is the primary target for reducing cardiovascular risk with lipid-modifying treatment 12 Baseline assessment including investigations Clinical assessment: Page 5 of 18

6 Medicine > Cardiology > Hyperlipidaemia, dyslipidaemia and smoking status alcohol consumption blood pressure body mass index or other measures of obesity (e.g. waist circumference) review medications, especially thiazide diuretics, ciclosporin Investigations: fasting total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol and triglycerides fasting blood glucose or HbA1C if known diabetes renal function liver function If transaminases are raised it is important to establish the reason. Non alcoholic fatty liver disease sometimes causes significantly raised transaminases, and commonly occurs with diabetes and obesity thyroid function tests (TSH) Plasma creatine kinase estimation is not necessary before starting or during treatment. 13 Primary care diagnostic criteria for FH after 2 fasting lipid profiles 3 months apart Primary care diagnosis Refer to FH Coordinator if the following criteria are present: Possible FH LDL >5.5 mmol/l in adult AND a triglyceride concentration less than 4.0 mmol/l (measurements either pre-treatment or highest on treatment) PLUS ONE OF THE FOLLOWING: family history of myocardial infarction before age 50 in 2nd degree relative or before age 60 in 1st degree relative family history of raised total cholesterol concentration above 8.0 mmol/l in 1st or 2nd degree relative Definite FH the above criteria plus tendon xanthomata (or evidence of these in 1st or 2nd degree relatives) and /or DNA-based evidence of an LDL receptor mutation, familial receptor defective apo-b100, or a PCSK 9 mutation in patient or 1st or 2nd degree relative 14 Formal risk assessment Risk equations are designed for estimating risk prior to an intervention. Risk calculation should not be used to re-calculate risk after an intervention (e.g. after smoking cessation, or treatment with a statin or anti-hypertensive agent). Risk equations should not be used for people who are already at high risk, eg because of: familial (FH) or other monogenic disorders of lipid metabolism age 75 years or older, who should be considered at increased risk of CVD, particularly if they smoke or have raised BP NICE CG67 does not recommend a specific risk assessment tool.( Options include: QRISK 2 risk calculator developed from UK general practice populations and updated annually modified Framingham risk equation 15 Treat secondary causes of dyslipidaemia Page 6 of 18

7 Medicine > Cardiology > Hyperlipidaemia, dyslipidaemia and Secondary causes of hyperlipidaemia include: diabetes (very common cause of high triglyceride and low HDL cholesterol concentrations) see local type 2 diabetes - management pathway nephrotic syndrome obstructive jaundice hypothyroidism Cushing's syndrome anorexia nervosa thiazide diuretics ciclosporin chronic renal failure 16 Refer to FH Coordinator for consideration of genetic testing The FH Coordinator will: discuss South Central criteria for genetic testing for FH and implication for patient and family discuss limitations of DNA and LDL- C testing draw up family pedigree gain consent for genetic testing enter own and family details on national genetic database initiate genetic testing (or testing for known familial mutation) Contact details: tel: fax: secure suzie.stuart@nhs.net 17 Estimated 10-year risk less than 20% - consider other factors Estimated cardiovascular risk should be subjectively refined, using clinical judgement, to take into account other factors, eg: low socioeconomic status (partially covered by postcode in QRISK-2) evidence of target organ damage other conditions that increase risk of CVD chronic kidney disease rheumatoid arthritis (covered in QRISK-2 SLE HIV treatment antipsychotic medication 18 Estimated 10-year risk 20% or greater High risk is defined as cardiovascular disease (CVD) risk of 20% or more over 10 years, using a recognised scoring tool such as QRISK 2 Page 7 of 18

8 Medicine > Cardiology > Hyperlipidaemia, dyslipidaemia and 19 Consider seeking specialist advice Consider seeking specialist advice in managing people with any of the following: severe mixed hyperlipidaemia cholesterol >7.5mmol/L triglyceride > 5mmol/L severe hypertriglyceridaemia serum triglyceride >10mmol/L resistant hyperlipidaemic states secondary hyperlipidaemia abnormal pretreatment liver enzymes (ALT >3x upper limit of normal) drug intolerance (to lipid-modifying drugs) lipodystrophy syndromes dyslipidaemia related to HIV people taking complex combinations of drugs with high risk of serious drug interaction with lipid modification therapy Consider requesting Advice and Guidance via Choose and Book as an alternative to an outpatient appointment. 20 Positive genetic screen Manage cholesterol using guidelines for 'Established cardiovascular disease' pathway on the left hand side of the current map. The goal is to reduce LDL cholesterol by 50% from pre-treatment values. Ensure patient has a full CVD risk factor assessment and management of other cardiovascular risk factors, including lifestyle advice. Refer to lipid clinic for management advice if unable to reduce LDL cholesterol to the recommended level (up to 20% of patients). 21 Negative genetic screen If genetic testing is negative, or reveals a mutation of uncertain significance but the phenotype is suggestive of FH, then cascade lipid testing of the family will be considered on the assumption they have a genetic mutation that has not yet been identified. This will be agreed after discussion between FH Coordinator and FH specialist. 22 Offer statin therapy as soon as possible The decision of whether to initiate statin therapy should be made after an informed discussion between the responsible clinician and the person about the risks and benefits of statin treatment, taking into account additional factors such as co-morbidities and life expectancy. Patients with clinical evidence of cardiovascular disease (CVD): offer lipid modification therapy as soon as possible do not delay to manage modifiable risk factors start treatment with simvastatin 40mg daily (or lower dose if potential drug interactions) consider alternative statin, such as pravastatin or atorvastatin, if simvastatin contraindicated or not tolerated. Pravastatin may be particularly helpful in those taking interacting medications, such as warfarin. If patient has acute coronary syndrome (ACS) with continuing 'episodes' despite meeting cholesterol targets, high intensity statin treatment (e.g atorvastatin 80mg) may be initiated in secondary care. Tolerability in primary care may be problematic following initiation, and review is therefore important. Contraindications to statins include: active hepatic disease Page 8 of 18

9 Medicine > Cardiology > Hyperlipidaemia, dyslipidaemia and transaminase levels three or more times the upper limit of normal. Do not routinely exclude from lipid therapy people with transaminases that are raised but less than three times the upper limit of normal unexplained persistent elevations of transaminases pregnancy lactation NB: women with FH should be advised that lipid-modifying drug treatment should not be taken if they are planning to conceive or during pregnancy, due to the potential risk of fetal abnormality year cardiovascular risk reassessed to be 20% or greater High risk is defined as cardiovascular disease (CVD) risk of 20% or more over 10 years, using a recognised scoring tool year cardiovascular risk less than 20% Low risk of cardiovascular disease (CVD): low risk is defined as: asymptomatic and under age 75 years without known CVD; and a calculated CVD risk, using a recognised scoring tool, of less than 10% over 10 years perform a risk assessment of people at low risk of CVD on an ongoing basis Provide information and advice for primary prevention of CVD: weight management, including healthy diet and physical activity smoking cessation with practical help and nicotine replacement therapy (NRT) where appropriate follow-up intervals consider lipid modification therapy if necessary use clinical judgement in deciding on further treatment of risk factors in people who are below the 20% CVD risk threshold NB: The largest number of CVD events will occur in people at low risk so primary prevention and continued risk assessment is extremely important. 25 FH Coordinator will organise cascade testing of family If genetic testing is positive, then FH coordinators will map the pedigree of the family and initiate cascade testing for FH. 26 Patient advice during statin therapy If patient develops muscle pain, weakness, or tenderness: advise patient to seek medical advice advise patient to stop taking lipid-modifying medication immediately if muscle symptoms are severe If patient develops: unexplained peripheral neuropathy features of interstitial lung disease: dyspnoea non-productive cough deterioration in general health, eg fatigue, weight loss or fever Discontinue statin and seek specialist advice. Page 9 of 18

10 Medicine > Cardiology > Hyperlipidaemia, dyslipidaemia and 27 Provide lifestyle advice Diet: Advise patients to eat a cardioprotective diet, comprising: fat intake 30% or less than total energy intake saturated fat intake 10% or less of total energy intake saturated fats should be replaced by monounsaturated and polyunsaturated fats cholesterol intake less than 300mg per day five portions of fruit and vegetables per day two portions of fish per week, including a portion of oily fish pregnant women should limit their intake of oily fish to two portions a week Physical activity: Recommend 30 minutes of at least moderate intensity exercise a day at least 5 days a week (or maximum safe capacity for those unable to manage the recommended level): advise that this can be broken down into 10-minute sessions (or more) and accumulated throughout the day suggest activities that can be easily incorporated into daily routine, eg: cycling using stairs brisk walking provide patient with support, encouragement, and any written information to assist in achieving recommended levels Weight management: offer overweight and obese patients support and advice to achieve healthy weight Alcohol consumption: advise men to limit their alcohol intake to 3-4 units a day advise women to limit their alcohol intake to 2-3 units a day advise avoiding binge drinking Smoking: Advise all people who smoke to stop smoking is an important risk factor for cardiovascular disease (CVD): offer referral to an intensive support service, eg NHS Stop Smoking Services if person is unable or unwilling to accept referral, offer pharmacotherapy for smoking cessation offer nicotine replacement therapy (NRT) or bupropion to increase the likelihood of long-term abstinence assess degree of addiction to guide use of NRTs advise minimising exposure to passive smoking describe cardiovascular and other disease risks of smoking provide information on approaches to smoking cessation, assess readiness to stop, and agree a specific plan and follow up arrangement 28 Provide lifestyle advice Diet: Advise patients to eat a cardioprotective diet, comprising: fat intake 30% or less than total energy intake saturated fat intake 10% or less of total energy intake saturated fats should be replaced by monounsaturated and polyunsaturated fats cholesterol intake less than 300mg per day five portions of fruit and vegetables per day Page 10 of 18

11 Medicine > Cardiology > Hyperlipidaemia, dyslipidaemia and two portions of fish per week, including a portion of oily fish pregnant women should limit their intake of oily fish to two portions a week Physical activity: Recommend 30 minutes of at least moderate intensity exercise a day at least 5 days a week (or maximum safe capacity for those unable to manage the recommended level): advise that this can be broken down into 10-minute sessions (or more) and accumulated throughout the day suggest activities that can be easily incorporated into daily routine, eg: cycling using stairs brisk walking provide patient with support, encouragement, and any written information to assist in achieving recommended levels Weight management: offer overweight and obese patients support and advice to achieve healthy weight Alcohol consumption: advise men to limit their alcohol intake to 3-4 units a day advise women to limit their alcohol intake to 2-3 units a day advise avoiding binge drinking Smoking: Advise all people who smoke to stop smoking is an important risk factor for cardiovascular disease (CVD): offer referral to an intensive support service, eg NHS Stop Smoking Services if person is unable or unwilling to accept referral, offer pharmacotherapy for smoking cessation offer nicotine replacement therapy (NRT) or bupropion to increase the likelihood of long-term abstinence assess degree of addiction to guide use of NRTs advise minimising exposure to passive smoking describe cardiovascular and other disease risks of smoking provide information on approaches to smoking cessation, assess readiness to stop, and agree a specific plan and follow up arrangement 29 Baseline assessment including investigations Clinical assessment: smoking status alcohol consumption blood pressure body mass index or other measures of obesity (e.g. waist circumference) review medications, especially thiazide diuretics, ciclosporin Investigations: fasting total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol and triglycerides fasting blood glucose or HbA1C if known diabetes renal function liver function If transaminases are raised it is important to establish the reason. Non alcoholic fatty liver disease sometimes causes significantly raised transaminases, and commonly occurs with diabetes and obesity thyroid function tests (TSH) Plasma creatine kinase estimation is not necessary before starting or during treatment. 31 Laboratory monitoring of cholesterol and liver function Page 11 of 18

12 Medicine > Cardiology > Hyperlipidaemia, dyslipidaemia and Check lipid profile: approximately eight weeks after initiation of treatment after each adjustment to treatment annually once the individual has reached optimal achievable target if fasting triglycerides are normal, monitor response with a non-fasting total cholesterol Measure liver function: prior to treatment within three months at 12 months annually thereafter Stop statin if serum ALT rises to >3x upper limit of the reference range. Do not routinely check serum creatine kinase: only monitor creatinine kinase in patients that have muscle symptoms If muscle symptoms, stop statin if creatine kinase is five times or more the upper limit of normal 32 Treat secondary causes of dyslipidaemia Secondary causes of hyperlipidaemia include: diabetes (very common cause of high triglyceride and low HDLc concentrations) nephrotic syndrome obstructive jaundice hypothyroidism Cushing's syndrome anorexia nervosa thiazide diuretics ciclosporin chronic renal failure 35 Consider adverse effects from statins Adverse events associated with statins include: headache altered liver function paraesthesia gastrointestinal (GI) effects (common, but rarely require stopping treatment), eg: abdominal pain flatulence diarrhoea nausea and vomiting rash and hypersensitivity reactions (both rare) muscle effects, eg: myalgia myositis myopathy Page 12 of 18

13 Medicine > Cardiology > Hyperlipidaemia, dyslipidaemia and severe muscle damage (rhabdomyolysis) very rare depression memory problems (NB not dementia) peripheral neuropathy interstitial lung disease The risk of myopathy is greater in: elderly patients (>65years) women patients with renal impairment or hypothyroidism patients who consume large quantities of alcohol those with a previous history of muscle problems with statins or other lipid-lowering drugs those with a family history of muscle disorder concomitant use of fibrates Note: patients should avoid consuming grapefruit juice while taking a statin. 36 Consider seeking specialist advice Consider seeking specialist advice in managing people with any of the following: severe mixed hyperlipidaemia cholesterol >7.5mmol/L triglyceride > 5mmol/L severe hypertriglyceridaemia serum triglyceride >10mmol/L resistant hyperlipidaemic states secondary hyperlipidaemia abnormal pretreatment liver enzymes (ALT >3x upper limit of normal) drug intolerance (to lipid-modifying drugs) lipodystrophy syndromes dyslipidaemia related to HIV people taking complex combinations of drugs with high risk of serious drug interaction with lipid modification therapy Consider requesting Advice and Guidance via Choose and Book as an alternative to an outpatient appointment. 37 Target for cholesterol during treatment Patients with clinical evidence of cardiovascular disease (CVD): use total cholesterol level of 5mmol/L as audit level to assess progress ideal target of total cholesterol less than 4mmol/L or LDL cholesterol less than 2mmol/L, although less than half of all people with CVD will eventually achieve this 38 Provide lifestyle advice As well as offering lipid modification therapy for primary prevention of cardiovascular disease (CVD), optimise management of other modifiable risk factors. Diet: Advise patients to eat a cardioprotective diet, comprising: Page 13 of 18

14 Medicine > Cardiology > Hyperlipidaemia, dyslipidaemia and fat intake 30% or less than total energy intake saturated fat intake 10% or less of total energy intake saturated fats should be replaced by monounsaturated and polyunsaturated fats cholesterol intake less than 300mg per day five portions of fruit and vegetables per day two portions of fish per week, including a portion of oily fish pregnant women should limit their intake of oily fish to two portions a week Physical activity: Recommend 30 minutes of at least moderate intensity exercise a day at least 5 days a week (or maximum safe capacity for those unable to manage the recommended level): advise that this can be broken down into 10-minute sessions (or more) and accumulated throughout the day suggest activities that can be easily incorporated into daily routine, eg: cycling using stairs brisk walking provide patient with support, encouragement, and any written information to assist in achieving recommended levels Weight management: offer overweight and obese patients support and advice to achieve healthy weight Alcohol consumption: advise men to limit their alcohol intake to 3-4 units a day advise women to limit their alcohol intake to 2-3 units a day advise avoiding binge drinking Smoking: Advise all people who smoke to stop smoking is an important risk factor for cardiovascular disease (CVD): offer referral to an intensive support service, eg NHS Stop Smoking Services if person is unable or unwilling to accept referral, offer pharmacotherapy for smoking cessation offer nicotine replacement therapy (NRT) or bupropion to increase the likelihood of long-term abstinence assess degree of addiction to guide use of NRTs advise minimising exposure to passive smoking describe cardiovascular and other disease risks of smoking provide information on approaches to smoking cessation, assess readiness to stop, and agree a specific plan and follow up arrangement 39 Drug therapy to achieve cholesterol target If cholesterol target is not achieved with standard doses of statins, then: simvastatin 80mg is no longer routinely recommended for safety reasons consider atorvastatin 20mg, titrating to 80mg daily if necessary if high dose atorvastatin is contraindicated or not tolerated, or does not achieve lower targets, consider adding 10mg ezetimibe statins can also be combined with a fibrate, especially fenofibrate. There is a slightly increased risk of myositis with this combination, and patients should be warned to discontinue the fibrate and statin if they experience any severe muscle pains or weakness 40 Offer statin therapy Page 14 of 18

15 Medicine > Cardiology > Hyperlipidaemia, dyslipidaemia and The decision of whether to initiate statin therapy should be made after an informed discussion between the responsible clinician and the person about the risks and benefits of statin treatment, taking into account additional factors such as co-morbidities and life expectancy. start treatment with simvastatin 40mg daily (or lower dose if potential drug interactions) consider alternative statin such as pravastatin 40mg or atorvastatin 20mg if simvastatin contraindicated, or not tolerated. Pravastatin may be particularly suitable for those on interacting medications such as warfarin. Contraindications to statins include: active hepatic disease transaminase levels three or more times the upper limit of normal unexplained persistent elevations of transaminases pregnancy lactation NB: women with FH should be advised that lipid-modifying drug treatment should not be taken if they are planning to conceive or during pregnancy, due to the potential risk of fetal abnormality. 41 Fasting serum triglycerides persistently >5mmol/L Persistently raised serum triglyceride contributes to an increased risk of cardiovascular disease. If lifestyle changes and statin treatment do not reduce fasting serum triglyceride below 5mmol/L, consider adding fenofibrate. N.B. poor glycaemic control with diabetes is a very common cause of increased plasma triglyceride concentrations. 42 Patient advice during statin therapy If patient develops muscle pain, weakness, or tenderness: advise patient to seek medical advice advise patient to stop taking lipid-modifying medication immediately if muscle symptoms are severe If patient develops: unexplained peripheral neuropathy features of interstitial lung disease: dyspnoea non-productive cough deterioration in general health, eg fatigue, weight loss or fever Discontinue statin and seek specialist advice. 43 Monitoring of cholesterol is NOT required Local advice is to follow NICE guidance, which does not require treatment to a target cholesterol or low density lipoprotein cholesterol for primary prevention (a so-called 'fire and forget' strategy). See NICE CG Statin intolerance or interactions Interactions If patient is prescribed medication that interferes with simvastatin metabolism, e.g amlodipine or diltiazem (see BNF for full list), consider: reducing statin dose Page 15 of 18

16 Medicine > Cardiology > Hyperlipidaemia, dyslipidaemia and trying alternative statin (e.g atorvastatin or pravastatin) ceasing statin treatment Statin intolerance If statin is not tolerated, consider changing to an alternative statin or reducing the dose. With multiple statin intolerances consider gradual introduction of rosuvastatin increasing the dose every 4 weeks as follows: 5 mg each week, then 5mg 3 times weekly, then 5mg alternate days, then 5mg daily If adverse effects occur, then reduce to the previous dose level. For some patients Intermittenttant use of rosuvastatin can significantly reduce the serum cholesterol. If the patient fails to tolerate even low dose rosuvastatin, consider: fenofibrate colestyramine ezetimibe Note: patients should avoid consuming grapefruit juice while taking a statin. 45 Laboratory monitoring monitoring of liver function Checking lipid profile is not essential. IF decision is reached with the patient to monitor response, then check: approximately eight weeks after initiation of treatment after each adjustment to treatment annually once the individual has reached optimal achievable target if fasting triglycerides are normal, monitor response with a non-fasting total cholesterol Measure liver function: prior to treatment within three months at 12 months annually thereafter Stop statin if serum ALT rises to >3x upper limit of the reference range. Do not routinely check serum creatine kinase: only monitor creatinine kinase in patients that have muscle symptoms If muscle symptoms, stop statin if creatine kinase is five times or more the upper limit of normal 46 Consider adverse effects from statins Adverse events associated with statins include: headache altered liver function paraesthesia gastrointestinal (GI) effects (common, but rarely require stopping treatment), eg: abdominal pain flatulence diarrhoea nausea and vomiting rash and hypersensitivity reactions (both rare) Page 16 of 18

17 Medicine > Cardiology > Hyperlipidaemia, dyslipidaemia and muscle effects, eg: myalgia myositis myopathy severe muscle damage (rhabdomyolysis) very rare depression memory problems (NB not dementia) peripheral neuropathy interstitial lung disease Note: patients should avoid consuming grapefruit juice while taking a statin. 47 Statin intolerance or interactions Interactions If patient is prescribed medication that interferes with simvastatin metabolism, e.g amlodipine or diltiazem (see BNF for full list), consider: reducing statin dose trying alternative statin (e.g atorvastatin or pravastatin) ceasing statin treatment Statin intolerance If statin is not tolerated, consider changing to an alternative statin or reducing the dose. With multiple statin intolerances consider gradual introduction of rosuvastatin increasing the dose every 4 weeks as follows: 5 mg each week, then 5mg 3 times weekly, then 5mg alternate days, then 5mg daily If adverse effects occur, then reduce to the previous dose level. For some patients Intermittenttant use of rosuvastatin can significantly reduce the serum cholesterol. If the patient fails to tolerate even low dose rosuvastatin, consider: fenofibrate colestyramine ezetimibe Note: patients should avoid consuming grapefruit juice while taking a statin. Page 17 of 18

18 Medicine > Cardiology > Hyperlipidaemia, dyslipidaemia and Key Dates Published: 13-Feb-2014, by Valid until: 30-Oct-2015 Evidence summary for Hyperlipidaemia, dyslipidaemia and References This is a list of all the references that have passed critical appraisal for use in the care map Hyperlipidaemia, dyslipidaemia and ID Reference 1 National Collaborating Centre for Primary Care (NCCPC). Lipid modification: Cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. Clinical guideline 67. London: NICE; DeMott K, Nherera L, Shaw EJ et al. Clinical guidelines and evidence review for familial : the identification and management of adults and children with familial. London: National Collaborating Centre for Primary Care (NCCPC) and Royal College of General Practitioners (RCGP); Joint British Societies (JBS). JBS 2: Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice. Heart 2005; 91 Suppl 5: v1-v Clinical Knowledge Summaries (CKS). Lipid modification - primary and secondary CVD prevention. Version 1.5. Newcastle upon Tyne: CKS; _answers_no_prescriptions# Contributors representing the Royal College of Physicians (RCP) National Institute for Health and Clinical Excellence (NICE). Statins for the prevention of cardiovascular events. Technology appraisal 94. London: NICE; Map of Medicine (MoM) Clinical Editorial team and Fellows. London: MoM; Medicines and Healthcare products Regulatory Agency (MHRA). Drug Safety Update: latest advice for all medicines users. London: MHRA; Abourbih S, Filion KB, Joseph L et al. Effect of fibrates on lipid profiles and cardiovascular outcomes: a systematic review. Am J Med 2009; 122: Jun M, Foote C, Lv J et al. Effects of fibrates on cardiovascular outcomes: a systematic review and metaanalysis. Lancet 2010; 375: National Institute for Health and Clinical Excellence (NICE). Ezetimibe for the treatment of primary (heterozygous-familial and non-familial). Technology appraisal 132. London: NICE; Page 18 of 18