Document Type: Unique Identifier: GUIDELINE Lipid ... · erythematous (SLE) or rheumatoid arthritis...

Document Type: Unique Identifier: GUIDELINE CORP/GUID/314

Version Number: 1

Title: Lipid Modification Therapy For The Precaution Of Cardiovascular Disease (CVD)

Status: Ratified

Scope: Classification: Cardiac and Stroke Networks in Lancashire & Cumbria – Network wide Organisational

Author/Originator and Title: Responsibility: Sean Mackey – Pharmacy Advisor Cardiac and Stroke

Networks Replaces: Description of amendments: New Guideline

Risk Assessment: Not Applicable

Name of Committee: Divisional/Directorate/

Date of Meeting: Working Group: 10/06/2009 Financial

Implications Cardiac Clinical Advisory Group

Not Applicable

Validated by: Validation Date: Sally Chisholm, Cardiac and Stroke Networks Programme Director 10/06/2009 Ratified by: Ratified Date: Date of Issue: Clinical Improvement Committee 07/09/2009 07/09/2009

Review Date: 01/09/2011

2009 2014 2015 2016 Review Dates: 2010 2011 2012 2013 2017 2018Review dates may alter if any significant changes are made

Does this document meet with the Race Relation Amendment Act (2000) Religious Discrimination Act, Age Discrimination Act, Disability Discrimination Act and Gender Equality Regulations? Not Applicable

Blackpool Fylde and Wyre Hospitals NHS Foundation Trust

Revision No: 1 Review Date: 0109/2011

I.D. No: CORP/GUID/314


Do you have the up to date version? See the intranet for the latest version of 18

1 PURPOSE.

This guideline ensures best practice advice on the care of adults at high risk of developing cardiovascular disease (CVD) and/or with established CVD. Treatment and care should take into account patients’ needs and preferences. People at high risk of CVD or with established CVD should have the opportunity to make informed decisions about their care and treatment, in partnership with their healthcare professionals.

2 SCOPE.

The guideline applies to treating people (aged 18 years and older) with CVD or without established CVD but who are at high risk of developing CVD due to a combination of cardiovascular risk factors including raised blood pressure, hypertension, diabetes, and/or who are overweight or obese. Excluded The guideline does not cover people:

• with familial hypercholesterolaemia (FH) and familial hypertriglyceridaemia

(familial lipoprotein lipase deficiency; familial apolipoprotein C-II deficiency) (e.g. consider FH if total cholesterol concentrations >7.5 mmol/l & personal or family history of premature coronary heart disease).

• with familial clotting disorders and/or other defined genetic disorders that increase cardiovascular risk

• who are at high risk of CVD or abnormalities of lipid metabolism as a result of endocrine or other secondary disease processes or as a result of drug treatment

• with lipid disorders considered to merit referral to secondary care for specialist assessment, clinical management and follow-up.

Please Note Assessment of modifiable risk factors and baseline tests applicable to both primary and secondary prevention Advice on diet and physical activity should be given in line with national recommendations.

3 GUIDELINE

3.1 INTRODUCTION

Trial evidence confirms statins reduce CVD events and total mortality irrespective of baseline risk. People at highest risk after acute myocardial infarction will have greater absolute benefit than people at lower risk who have not yet had an event. Dietary change, physical activity and drugs can reduce Blood cholesterol. This guideline addresses the identification of those at high risk, and the modification of lipids in these people and people with established CVD. Treatment should be aimed at reducing overall risk. Please Note It is important to stress that a multifactorial approach that addresses all risk factors yields most benefit.






When considering therapy for lipid modification, all modifiable cardiovascular risk factors should be considered and their management optimized (including lifestyle measures). This should be done before offering lipid modification therapy for primary prevention. For secondary prevention, lipid modification therapy should be offered and should not be delayed by management of modifiable risk factors.

Assessment should include evaluation of:

• smoking status • alcohol consumption • blood pressure • Body Mass Index or other measure of obesity (refer to NICE Obesity guideline, No.

CG43, 2006) • fasting total cholesterol, Low Density Lipoprotein (LDL) cholesterol, High Density

Lipoprotein (HDL) cholesterol and triglycerides (if fasting levels are not already available)

• fasting blood glucose • renal function • liver function (transaminases). • Secondary causes of dyslipidaemia should be considered and excluded before

starting lipid therapy. • Ethnicity, body mass index and family history of premature heart disease should also

be routinely recorded in medical records.

3.2 KEY RECOMMENDATIONS - PRIMARY PREVENTION OF CVD (EXCLUDING DIABETIC PATIENTS)

3.2.1 Prioritisation For Assessment With Risk Calculator For the primary prevention of cardiovascular disease (CVD) in primary care, a systematic strategy should be used to identify individuals aged 40-74 who are likely to be at high risk. Individuals should be prioritised on the basis of an estimate of their CVD risk before a full formal risk assessment.

This should be calculated using the recommended risk equation utilising CVD risk factors recorded in their primary care electronic medical record. The following variables should be used for formal estimation of CVD risk with the Framingham 1991 equations:

• age • sex • smoking status • systolic blood pressure (average of two readings (if raised), ideally over several

visits) • total cholesterol • HDL cholesterol • presence of left ventricular hypertrophy (only if already known, no need for baseline

ECG)






Opportunistic assessment should not be the main strategy used in primary care to identify CVD risk in unselected people. A systematic approach should be adopted as recommended in the Department of Health Vascular Risk Programme. This level of risk should be estimated using an appropriate risk calculator, or by clinical assessment for people for whom an appropriate risk calculator is not available or appropriate.

3.2.2 Groups for which clinical assessment is preferable to risk calculator The following groups should be assessed clinically in preference to using a risk calculator: • Age over 75 years

• Discuss risks and benefits and routinely offer a statin (likely to benefit), especially if

concurrent high blood pressure and/or smoking. Take into account informed preference, and other co-morbidities that might make statin therapy inappropriate.

• Concurrent medical conditions or treatments

• Human Immunodeficiency Virus (HIV), autoimmune disorders (e.g. systemic lupus

erythematous (SLE) or rheumatoid arthritis (RA)), or being treated with anti-psychotic medication.

3.2.3 Recording and repeating risk assessments The assessment of CVD risk should be made using Framingham 1991 10-year risk equations. This is currently under constant review by NICE, as Framingham tends to overestimate risk in the UK population, and the range of risk factors included differs between different risk calculators. Practices should calculate 10-year cardiovascular risk using an accepted risk calculator based upon Framingham 1991.

Please Note As a guide, risk scoring should be repeated every year if a patients risk is between 11-19%, and every 3-5 years if it less than 10%, although this should be tailored for individuals based upon clinical judgment.

3.2.4 Other factors affecting risk calculator score The risk score used to inform treatment decisions, particularly if near to the threshold, should take into account other factors that:

• may predispose the person to premature CVD • may not be included in calculated risk estimates.

Conversely, healthcare professionals should also be aware that Framingham 1991 risk equations may overestimate risk in UK populations.

Other factors to be taken into account include:






Family History

The estimate of cardiovascular risk should be increased by a factor of 1.5 in individuals with a first-degree relative with a history of premature coronary heart disease (age at onset younger than 55 in fathers, sons or brothers or younger than 65 in mothers, daughters or sisters). The estimated CVD risk should be increased by a factor of between 1.5 and 2.0 if more than one first-degree relative has a history of premature CHD

Ethnicity The estimated cardiovascular risk for South Asian men should be increased by a factor of 1.4.

Socioeconomic Status

Although this should be taken into account when risk assessing, but there are no current recommended adjustments to the score. Framingham underestimates the score in deprived populations.

Current Antihypertensive, Lipid Lowering Medication, Stopped Smoking

Cardiovascular risk may be underestimated in people taking antihypertensive or lipid lowering drugs, or who have recently stopped smoking. Therefore, it is important to try and estimate CVD risk retrospectively, by using the pre-treatment value of a risk factor, whenever this can be found in the person’s medical record. If there is no record of the pretreatment value then as a rule of thumb assume for blood pressure that it was at least 160 mm Hg, and for the total cholesterol to HDL cholesterol ratio assume that it was at least 6. These values will give a pragmatic but conservative retrospective estimate of CVD risk.

Other risk factors: Severe obesity (body mass index greater than 40 kg/m

2) affects CVD

risk and should be considered when using risk scores to inform treatment decisions (see 'Obesity', NICE clinical guideline 43).

Recommendations For Lipid Measurement And Referral A random (not fasting) cholesterol test is required under the NHS Health Check programme to help ensure maximum take-up. Before commencing statin treatment, a fasting lipid profile is recommended to record total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides. The results of the fasting test may, in a few cases, drop the individual’s previous risk score below 20%.In order to measure LDL at present, a fasting specimen is necessary which gives triglyceride measurement. If however the person’s fasting triglyceride level is already known to be 2mmol/l or less a fasting lipid sample is not required. The decision to offer treatment should be made as soon as practicable after full risk factor assessment unless patient choice or clinical factors indicate that treatment is not appropriate. Where a statin is started after an acute event, it is appropriate to measure a fasting lipid sample at around 3 months and statin treatment should not be delayed.

People in whom familial hypercholesterolaemia or other monogenic familial disorders are suspected should be considered for further investigation and/or specialist review. People with severe hyperlipidaemias should be considered for further investigation and/or specialist review. Provision Of Patient Information Regarding Risks And Benefits Of Treatment The discussion relating to the consultation on risk assessment and the person’s decision should be documented. People should be offered information about their absolute risk of CVD and about the absolute benefits and harms of an intervention over a 10-year period. This information should be in everyday language, with any jargon clearly explained, and in a form that:

• presents individualised risk and benefit scenarios • presents the absolute risk of events numerically • uses appropriate diagrams and text.

The NPC has produced risk factor charts (NPCi patient decision aids) which may be helpful. Once an individual has had their risk factors measured and is found to be in a high- risk group for which active management is recommended, it may require several consultations and some time may be necessary for this information to be conveyed and assimilated and other clinical issues addressed. If the person’s CVD risk is considered to be at a level that merits intervention but they decline the offer of treatment, they should be advised that their CVD risk should be considered again in the future.

Statin Therapy In Primary Prevention (Excluding Diabetic Patients) Please Note Before offering lipid modification therapy for primary prevention, all other modifiable CVD risk factors should be considered and their management optimised if possible (page 1) Statin therapy is recommended as part of the management strategy for the primary prevention of CVD for adults who have a 20% or greater 10-year risk of developing CVD. This level of risk should be estimated using an appropriate risk calculator, or by clinical assessment for people for whom an appropriate risk calculator is not available or appropriate (for example, older people, people with diabetes or people in high-risk ethnic groups). The decision 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. If statin treatment is appropriate, it should be offered as soon as practicable after a full risk factor assessment.

Simvastatin should be used at 40mg daily

Pravastatin 40mg daily should be used as a first line alternative where intolerance or potential drug interactions expose the patient to high risk of myopathy (see appendix 1 for






http://www.npci.org.uk/therapeutics/cardio/cdlipids/patient_decision_aids/patient_decision_aid1.php

simvastatin drug interaction advice). Alternatively a lower dose of simvastatin may be used where appropriate.

A target for total or LDL cholesterol is not recommended for people who are treated with a statin for primary prevention.

Once a person has been started on a statin for primary prevention, repeat lipid measurement is unnecessary. Clinical judgement and patient preference should guide the review of drug therapy and whether to review the lipid profile.

Other statins or high intensity statins should not be routinely offered in primary prevention. In addition, the use of an anion exchange resin, fibrate, fish oil supplement or nicotinic acid either alone, or in combination with a statin should not be offered for the primary prevention of CVD.

If patients have co-morbid conditions, which significantly reduce their life expectancy, it may be reasonable to stop statins in those circumstances following discussion with the patient and/or carers. Fibrates or anion exchange resins should not routinely be recommended for primary prevention of CVD.

3.3 KEY RECOMMENDATIONS - SECONDARY PREVENTION OF CVD (EXCLUDING DIABETICS) Please Note For secondary prevention, lipid modification therapy should be offered and should not be delayed by management of modifiable risk factors.

Blood tests and clinical assessment should be performed, and co-morbidities and secondary causes of dyslipidaemia should be treated. See page 1 for list of assessments.

The responsible clinician should discuss with the person about the risks and benefits of statin treatment, taking into account additional factors such as co-morbidities and life expectancy. Statin therapy is recommended for adults with clinical evidence of CVD.

• Subject to current evidence, statin treatment should be life-long • Statins should be started now regardless of when the initial event occurred

Treatment with a statin should therefore be offered to patients in the following groups:

• after myocardial infarction, or new-onset angina • with chronic heart failure AND known atherosclerotic disease in combination. • with chronic stable angina • after ischaemic stroke or transient ischaemic episode • with peripheral arterial disease











• Simvastatin 40mg daily first line should be offered to all patients with stable cardiovascular disease (incl. patients following an acute stroke**)

• Atorvastatin 80mg daily should be offered to all patients immediately following an

acute coronary syndrome, where this dose is not contra-indicated. It should be continued for 6 months and then reviewed and if considered stable then stepped down to Simvastation 40mg daily

**Statins following a stroke:

• Do not start statin treatment immediately after an acute stroke. The consensus of the NICE Guideline Development Group is that it would be safe to start statins after 48 hours.

• Continue statin treatment for people with acute stroke who are already taking statins.

Pravastatin 40mg daily should be used as a first line alternative where intolerance or potential drug interactions expose the patient to high risk of myopathy (see appendix 1 for simvastatin and atorvastatin drug interaction advice). Alternatively a lower dose of simvastatin may be used where appropriate. If patients have co-morbid conditions, which significantly reduce their life expectancy, it may be reasonable to stop statins in those circumstances following discussion with the patient and/or carers.

Why Are ALL Patients With Stable Cardiovascular Disease Not Immediately Offered A High Intensity Statin Such As Simvastatin 80mg Or Atorvastatin 40mg/80mg? NICE guidance clearly states that use of higher intensity statins is not cost-effective compared to low intensity statin therapy when used in all patients with stable coronary artery disease (£27,840/QALY). In other words, it is not a good use of resources to use the range of high intensity statins available to treat patients with established cardiovascular disease, due to the high cost of these statins, and the marginal benefit over standard intensity statins such as simvastatin 40mg daily. What constitutes higher intensity statins? NICE clearly states that ‘Higher intensity statins’ are statins used in doses that produce greater cholesterol lowering than simvastatin 40 mg, for example simvastatin 80 mg and atorvastatin 40mg/80mg. Who should be offered a high intensity statin, and when?






• Unstable Cardiovascular Disease (e.g. ACS which includes STEMI, NSTEMI

and unstable angina which requires admission)

• Atorvastatin 80mg daily should be started immediately following diagnosis without waiting for baseline lipid levels.

Stable Cardiovascular Disease (and patients immediately following an acute stroke)

• NICE have only endorsed dose titration to simvastatin 80mg in those patients with stable cardiovascular disease. This should be considered when triggered by a total cholesterol of >4mmol/l AND a LDL cholesterol of >2mmol/l by using simvastatin 40mg. Even with a dose titration to simvastatin 80mg, over 50% of patients will still not reach a total cholesterol of 4mmol/l or an LDL cholesterol of 2mmol/l. NICE do not recommend further titration or use of other high intensity statins to reach these targets, as this is not a cost effective use of resources.

• Only a titration strategy (e.g. simvastatin 40mg to 80mg) based on an initial

target total cholesterol of 4mmol/l was found to be cost-effective compared with a fixed dose strategy of low intensity statins, but ONLY if titrating using generic drugs, not branded drugs.

Special Very High Risk Groups under specialist management

• Although patients with lipid disorders that require specialist management are excluded from this guideline, there are some patients who are at a much greater elevated level of risk compared to the general stable CAD population that require specialist input and management. As their risk is still so elevated, futehr reductions in absolute risk by using higher intensity statins are likely to be cost-effective (as this is related to absolute reductions in risk rather than relative reductions). Cardiology specialists have the discretion therefore to use higher intensity statin therapy e.g. atorvastatin 80mg/day in selected higher risk patients.

Which high intensity statin should be offered?

• Unstable Cardiovascular Disease (e.g. ACS which includes STEMI, NSTEMI

and unstable angina which requires admission)

• Atorvastatin 80mg daily first line (chosen because of its greater evidence base in this population)

• The immediate use of high intensity statins (both simvastatin and atorvastatin

80mg) compared with low intensity statins in patients with ACS is cost-effective.

Stable Cardiovascular Disease

• The ONLY high intensity statin that should be offered in stable cardiovascular disease is simvastatin 80mg. Atorvastatin should not be offered.

• The ONLY high intensity statin found to be cost-effective in stable CAD by NICE is simvastatin 80mg daily. Atorvastatin 80mg should not be offered to stable patients with CAD. In patients with stable CAD, atorvastatin 80 mg is not cost-effective using a £20,000/QALY threshold. However, the use of generic simvastatin 80 mg makes the model highly cost-effective. Thus cheaper generic high intensity statins such as simvastatin 80mg may be used in patients with stable CAD who have not reached target, whereas atorvastatin should not.

3.4 KEY RECOMMENDATIONS PRIMARY & SECONDARY PREVENTION OF

CVD IN TYPE I AND II DIABETES

1. Primary Prevention in Diabetics

Before offering lipid modification therapy for primary prevention, all other modifiable CVD risk factors should be considered and their management optimised if possible (see page 1). The decision 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. If statin treatment is appropriate, it should be offered as soon as practicable after a full risk factor assessment. Consider to be at high CV risk unless all of the following apply:






● not overweight (tailor with body-weight-associated risk assessment according to ethnic group) ● normotensive (< 140/80 mmHg in absence of antihypertensive therapy) ● no microalbuminuria ● non-smoker ● no high-risk lipid profile ● no history of CV disease

Pravastatin 40mg daily

Simvastatin 40mg daily should be offered to all adult type I & II diabetics without established cardiovascular disease, who are at high cardiovascular risk.

should be used as a first line alternative where intolerance or potential drug interactions expose the patient to high risk of myopathy (see appendix 1 for simvastatin drug interaction advice). Alternatively a lower dose of simvastatin may be used where appropriate. Risk Assessment For Those At A Lower Cardiovascular Risk If the person is considered not to be at high cardiovascular risk (meets the criteria above), then estimate their cardiovascular risk annually using the UK Prospective Diabetes Study (UKPDS) risk engine (see UKPDS risk engine).

Simvastatin 40mg daily should also be offered to those diabetics in whom the cardiovascular risk exceeds 20% over 10 years

http://www.dtu.ox.ac.uk/index.php?maindoc=/riskengine/

Consider using cardiovascular risk estimates from the UKPDS risk engine for educational purposes when discussing cardiovascular complications with the individual.

Simvastatin Dose Titration In Diabetics In Primary Prevention NICE have only endorsed dose titration to simvastatin 80mg in those diabetic patients initiated with simvastatin 40mg daily who have not reached a total cholesterol of 4mmol/l or a LDL cholesterol of 2 mmol/l by using simvastatin 40mg. Further dose titration to target in primary prevention in diabetics is NOT endorsed by NICE. Please Note Atorvastatin or other statins should not be offered to primary prevention patients with diabetes.

2. Secondary Prevention in Diabetics

For secondary prevention in patients with diabetes, lipid modification therapy should be offered and should not be delayed by management of modifiable risk factors.

Blood tests and clinical assessment should be performed, and co-morbidities and secondary causes of dyslipidaemia should be treated. See page 1 for list of assessments.

The responsible clinician should discuss with the person about the risks and benefits of statin treatment, taking into account additional factors such as co-morbidities and life expectancy. Statin therapy is recommended for adults with clinical evidence of CVD.

• Subject to current evidence, statin treatment should be life-long • Statins should be started now regardless of when the initial event occurred

Treatment with a statin should therefore be offered to all diabetic patients in the following groups:

• after myocardial infarction, or new-onset angina • chronic heart failure AND known atherosclerotic disease in combination. • chronic stable angina • after ischaemic stroke or transient ischaemic episode • peripheral arterial disease






WWhich diabetics treated for secondary prevention should be offered a high intensity statin, and when?

• Simvastatin 40mg daily first line should be offered to all patients with diabetes and stable cardiovascular disease (incl. patients immediately following an acute stroke)

• Atorvastatin 80mg daily should be offered to all diabetic patients immediately following an acute coronary syndrome, where this dose is not contra-indicated. It should be continued for 6 months and then reviewed and if considered stable then stepped down to Simvastation 40mg daily

http://www.dtu.ox.ac.uk/index.php?maindoc=/riskengine/






• Diabetes & Unstable Cardiovascular Disease (e.g. ACS which includes STEMI, NSTEMI and unstable angina which requires admission)

• Atorvastatin 80mg daily should be started immediately following diagnosis

without waiting for baseline lipid levels. • Diabetics with stable cardiovascular disease (and diabetic patients

immediately following an acute stroke) NICE have endorsed dose titration to simvastatin 80mg in those patients with stable cardiovascular disease who have not reached a total cholesterol of 4mmol/l or a LDL cholesterol of 2 mmol/l by using simvastatin 40mg.

NICE have only endorsed dose titration to atorvastatin 80mg daily in those diabetic patients titrated to simvastatin 80mg daily who have not reached a total cholesterol of 4mmol/l or a LDL cholesterol of 2 mmol/l by using simvastatin 80mg.

4 ATTACHMENTS.

Appendix 1 – statin interactions Appendix 2 – Cardiac and Stroke Networks Quick Reference Lipid Guidelines Appendix 3 – References Appendix 4 - Consultation

5 ELECTRONIC AND MANUAL RECORDING OF INFORMATION.

Database for Policies, Procedures, Protocols and Guidelines Archive/Policy Co-ordinators office Archived at: Cardiac & Stroke Networks in Lancashire & Cumbria office, Room 176, Preston Business Centre, Watling Street Road, Preston PR2 8DY or via the Cardiac and Stroke Networks website – www.csnlc.nhs.uk

6 LOCATIONS THIS DOCUMENT ISSUED TO.

Copy No Location Date Issued 1 Intranet 07/09/2009 Wards and departments

7 OTHER RELEVANT /ASSOCIATED DOCUMENTS.

Procedure No.

Title

None






8 AUTHOR//DIVISIONAL/DIRECTORATE MANAGER APPROVAL.

Issued By Sean Mackey Checked By Sally Chisholm

Job Title Pharmacy Advisor Job Title Programme Director, Cardiac & Stroke Networks in Lancashire & Cumbria

Signature Signature

Date September 2009 Date September 2009






Appendix 1 Contra-indications or intolerance to statins

Where statins are not tolerated or contra-indicated use of single agent ezetimibe, fibrates or anion exchange resins may be considered. For the purposes of this guidance, intolerance to initial statin therapy should be defined as the presence of clinically significant adverse effects from statin therapy that are considered to represent an unacceptable risk to the patient or that may result in compliance with therapy being compromised. Adverse effects include evidence of new-onset muscle pain (often associated with levels of muscle enzymes in the blood indicative of muscle damage), significant gastrointestinal disturbance or alterations of liver function tests (e.g. greater than twice the upper limit of normal).

Monitoring of creatine kinase

Routine monitoring of creatine kinase is not recommended in asymptomatic patients who are being treated with a statin. People who are being treated with a statin should be advised to seek medical advice if they develop muscle symptoms (pain, tenderness or weakness). If this occurs creatine kinase should be measured. Monitoring of Liver Function Baseline liver enzymes should be measured before starting a statin. Liver function enzymes should be measured within six months of starting treatment and again at 12 months but not again unless clinically indicated. People who have raised liver enzymes (transaminases) should not routinely be excluded from statin therapy. Peripheral neuropathy Statins should be discontinued in people who develop an unexplained peripheral neuropathy and further advice from a specialist should be sought. Renal dysfunction Patients with CKD and established macrovascular disease should receive treatment with a statin as per guidance above.

Patients with CKD who do not have diabetes and who do not have established macrovascular disease should be offered the options of treatment with a statin if the estimated 10-year risk of cardiovascular disease is >=20%. Choice of statin in renal dysfunction Chronic kidney disease (CKD) incorporates those with moderate, severe or established renal failure as below.






Drug doses are based on information from the Renal Handbook17:

• Moderate impairment; eGFR 30–59 mL/min/1.73 m2 – simvastatin 40mg • Severe impairment: eGFR 15–29 mL/min/1.73 m2 – simvastatin 40mg • Established renal failure (ERF): eGFR <15mL/min/1.73 m2 or on dialysis –

simvastatin 10mg first line or atorvastatin 10mg • Transplant patients, especially those taking ciclosporin, should receive atorvastatin

in a dose no greater than 10mg. Please Note These recommendations may differ from information provided by individual manufacturers

Drug Interactions (Please note, drug interactions for statins other than simvastatin and atorvastatin have not been included here, as they are not recommended for use in this guideline. Please consult the SPC for these drugs for information about their drug interactions.) If a person taking a statin starts taking additional drugs, or needs treatment for a concomitant illness that interferes with metabolic pathways or increases the propensity for drug and food interactions, consider reducing the dose of the statin, or temporarily or permanently stopping it.

Simvastatin and atorvastatin: interactions (MHRA Advice) Many important interactions for simvastatin (Zocor) and atorvastatin relate to drugs that inhibit or induce metabolism via the cytochrome P450 (CYP3A4) enzyme, or that affect transport proteins. Starting dose If co-prescription with a drug that increases systemic exposure to statins is unavoidable, it is particularly important to start on the lowest statin dose. For atorvastatin and simvastatin the starting dose is 10 mg daily. Maintenance doses

The table gives important dose restrictions for atorvastatin and simvastatin when used in combination with other drugs. Both drugs interact with grapefruit juice.

Medicines that reduce plasma concentrations of simvastatin and atorvastatin

Inducers of CYP3A4 (e.g., efavirenz, rifampicin, St John’s wort) may reduce plasma concentrations of simvastatin and atorvastatin. Colestipol reduces plasma levels of atorvastatin, but lipid-lowering effects may be greater than when either drug is given alone. Important interactions to consider with all statins






Warfarin/coumarins

Statins may affect coumarin anticoagulation and increase the risk of haemorrhagic events. Patients who are receiving warfarin should have INR monitoring before starting statins and regularly throughout treatment, especially with statin dose changes. However, for pravastatin (Lipostat), which is not metabolised by cytochrome P450, warfarin interaction is less of a concern.

Fibrates

The use of fibrates alone is occasionally associated with myopathy; use with statins may increase this risk. Furthermore, gemfibrozil increases systemic exposure to simvastatin, atorvastatin. Careful monitoring is therefore needed, and maximum daily dose of simvastatin is 10 mg daily when used with fibrates (except fenofibrate).

Ezetimibe

Ezetimibe has no pharmacokinetic interaction with statins. However, ezetimibe alone is associated with a risk of myopathy and an additive risk with statins cannot be ruled out.

Other important interactions with pravastatin

Pravastatin

Pravastatin is not associated with cytochrome P450 interactions. Caution is needed with ciclosporin, erythromycin, and clarithromycin. Cholestyramine and colestipol decrease plasma levels of pravastatin.

Contraindications

Pregnancy and lactation - before considering statin treatment, underlying diseases should be specifically excluded e.g. thyroid disease

Caution

Concurrent diseases/conditions which indicate caution should be used include: renal impairment (see previous), myalgia, rhabdomyolysis, myositis, raised liver enzymes, liver disease, diabetes with evidence of hepatic fatty changes, heavy exercise, excessive alcohol intake, debilitated status or trauma, ischaemia reperfusion and pancreatitis

APPENDIX 2

Lancashire & South Cumbria Cardiac Network Full Lipid Modification Guideline

June 2009

What is the first line choice?

Simvastatin 40mg/day (except in Acute Coronary Syndrome cases) (where drug interactions or intolerance preclude use, offer a lower dose or pravastatin 40mg) What About ‘Treating To Targets’? • No target levels for primary prevention of CVD

• For secondary prevention of CVD NICE has not specifically set a

target of “4 or 2” in non-diabetics

o However if TC if still >4mmol/L or LDL-C >2mmol/L on simvastatin 40mg, discuss with patient fully the small additional benefits against the possible potential side-effects (e.g. myopathy) of using higher intensity therapy (eg simvastatin 80mg)

o NICE recognise that more than 50% of patients will still have a TC >4mmol/L and LDL-C >2mmol/L on simvastatin 40mg/80mg and should not routinely be offered an alternative branded statin.

o NICE has set an ‘audit’ target of total cholesterol of <5 mmol/L.

When would you offer a high intensity statin treatment? • Acute Coronary Syndrome – Atorvastatin 80mg/day for 6 months then review to simvastatin

40mg/day • Patients with Diabetes - if TC >4mmol/L and LDL-C >2mmol/L on simvastatin then titrate with a

high intensity statin as per local formulary • Very High Risk Patients - Cardiology specialists have the discretion to initiate higher intensity

statin therapy in selected high risk patients. Measuring Lipid Levels A baseline fasting lipid level is recommended in primary prevention, whereas in secondary prevention, the statin should be started without waiting for a lipid measurement. In secondary prevention, once a statin has been started it is appropriate to measure a fasting lipid sample at around 3 months. Familial Hypercholesterolaemia Familial hypercholesterolaemia should be suspected if total cholesterol >7.5 mmol/l & personal or family history of premature coronary heart disease.(NB. This guideline is not applicable to this group of individuals) Monitoring of statin therapy No need to routintely test creatine kinase levels in asymptomatic patients. Liver function tests (LFTs) should be measured at the start of treatment, and then again at 3 and 12 months, but not thereafter unless clinically indicated. Discontinue statin if peripheral neuropathy develops.

Use simvastatin 40mg when eGFR 15 -60mL/min, below this reduce dose to simvastatin 10mg or use atorvastatin 10mg. Advise people to seek medical advice if they develop muscle pain, tenderness or weakness Cautions Concurrent diseases/conditions which indicate that caution should be used include: renal impairment (see previous), myalgia, rhabdomyolysis, myositis, raised liver enzymes, liver disease, diabetes with evidence of hepatic fatty changes, heavy exercise, excessive alcohol intake, debilitated status or trauma, ischaemia reperfusion and pancreatitis Contraindications Pregnancy (& women likely to become pregnant) and lactation. NB. Before considering statin treatment in patients, possible underlying diseases should be specifically excluded e.g. thyroid disease.

Lipid Modification in NON-DIABETICS

ESTABLISHED CARDIOVASCULAR DISEASE

ACUTE CORONARY SYNDROME (NSTEMI, STEMI, Unstable Angina)

Before offering lipid modification therapy optimise the management of other modifiable risk factors if possible. Give information about pt’s absolute risk of CVD & the likely absolute benefits & harms of treatment in ways which they understand. Use the NPCi patient decision aids from www.npci.org.uk to illustrate risk/benfits

Offer Simvastatin 40mg/day If becoming pregnant is a possibility, discuss issues

surrounding statin use and agree next step with the woman.

Offer Simvastatin 40mg/day If becoming pregnant is a possibility, discuss issues surrounding statin use and agree next step with the

woman. Higher intensity statins should NOT be used.

No need to recheck cholesterol (No target)

Consider Simvastatin 80mg/day

Remain on simvastatin 80mg/day ONLY for patients intolerant (e.g. significant myalgia) to the higher dose of simvastatin 80mg, or for very high risk patients consider an alternative higher intensity statin. Higher intensity statins should not routinely be used

Initiate a higher intensity statin Atorvastatin 80mg/day

If there are potential drug interactions with simvastatin 40mg then offer pravastatin 40mg. Ezetimibe, fibrates, anion exchange resins (or nicotinic acid only for secondary prevention) may be considered ONLY where statins cannot be tolerated.

Check LFTs prior to treatment and at 3 & 12 months only.

Any decision to offer this higher simvastatin dose should take into account the patient's compliance, informed preference, comorbidities, multiple drug therapy & interactions, and the benefits and risks of treatment. Use the NPCi patient decision aid (www.npci.org.uk) to illustrate small additional benefits & risk of myopathy.

Trigger Point for further discussion with patient If TC >4mmol/L AND LDL >2mmol/L on

simvastatin 40mg/day Review back to simvastatin 40mg/day 6 months after last event

(Then treat as per ‘Established CVD’ algorithm)

Identify adults aged between 40 & 74 with a CVD risk >20% Use either Practice computer Framingham based

system or use the Joint British Societies risk

PRIMARY PREVENTION

http://www.bhsoc.org/Cardiovascular_Risk_Charts_and_Calculators.stm

Lipid Modification in People with Diabetes

Consider to be at high CV risk unless all of the following apply: ● not overweight (tailor with body-weight-associated risk assessment according to ethnic group)

ACUTE CORONARY SYNDROME (NSTEMI, STEMI, Unstable Angina)

● normotensive (< 140/80 mmHg in absence of antihypertensive therapy)

● no microalbuminuria

● non-smoker

Initiate a higher intensity statin Atorvastatin 80mg/day

● no high-risk lipid profile

Not high risk of CVD High risk of CVD or

established CVD

Offer Simvastatin 40mg nocte If becoming pregnant is a possibility, discuss issues surrounding

statin use and agree next step with woman. Re-check lipid profile and LFTs after 3 months and thereafter annually.

No need to recheck LFTs after 12 months.

Assess CV risk using UKPDS

risk engine

CV risk >20% over

If TC>4mmol/l or LDL >2mmol/l

Consider Simvastatin 80mg nocte. Only consider higher intensity statins if existing or newly

diagnosed CV disease. Re-check lipid profile and LFTs after 3 months and thereafter annually.

No need to recheck LFTs after 12 months.

Any decision to offer this higher simvastatin dose should take into account the patient's compliance, informed preference,

comorbidities, multiple drug therapy & interactions, and the benefits and risks of treatment. Use the NPCi patient decision aid

(www.npci.org.uk) to illustrate small additional benefits & risk of myopathy.

Review back to previous statin & dose 6 months after last event

Triglycerides • >4.5mmol/L offer fibrate first • 2.3-4.5mmol/L despite statin add fibrate (monitor carefully)

If there are potential drug interactions or simvastatin 40mg is poorly tolerated then offer Pravastatin 40mg daily depending on local formulary choice. Ezetimibe, fibrates, anion exchange resins or nicotinic acid may be considered where statins cannot be used.

Omega-3 fish oils/nicotinic acid also used by specialists

http://www.npci.org.uk/





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Appendix 3 References

NICE guidance CG67 LIPID MODIFICATION: Cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease Full Guideline May 2008 http://www.nice.org.uk/nicemedia/pdf/CG67FullGuideline1.pdf

1. http://www.nice.org.uk/nicemedia/pdf/TA094guidance.pdf 2. http://guidance.nice.org.uk/TA132 3. http://guidance.nice.org.uk/CG48

http://www.nice.org.uk/nicemedia/pdf/CG67FullGuideline1.pdf

http://www.nice.org.uk/nicemedia/pdf/TA094guidance.pdf

http://guidance.nice.org.uk/TA132

http://guidance.nice.org.uk/CG48





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Appendix 4

Consultation B Hemmings Pharmacist N Tidy Clinical Improvement Co-ordinator M Reid Clinical Librarian G Wood Archivist/Policy Co-ordinator

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