Statins for the prevention of atherosclerosis

High risk patients without established cardiovascular disease (CVD)

For primary prevention, therapy with a statin should be discussed with patients whose predicted cardiovascular disease risk over 10 years is 20% or more using ASSIGN or JBS3 risk calculators. Patients with rheumatological disease (RA/SLE): estimate the risk using ASSIGN, ticking the box for rheumatoid arthritis (RA).

Patients with diabetes and/or ischaemic stroke should be treated as Patients with Established Vascular Disease and/or Diabetes and/or Ischaemic Stroke.

Patients with chronic kidney disease: follow local guidance for this patient group

Screen for potential candidates for treatment. These are adults who:

smoke – stopping smoking will dramatically reduce cardiovascular risk (more than any other intervention) and improve quality of life. Appropriate measures to support stopping smoking should therefore be considered first-line in all patients who smoke.
are hypertensive.
have a family history of premature coronary artery disease (ie MI or CABG in first degree relative under 60).

Discuss treatment options with the patient taking into consideration that the benefits of therapy, eg absolute reductions in risk of heart attack and stroke are small and may be outweighed by the risk of side-effects, eg muscle pain and development of diabetes mellitus.

*SUPPLEMENTARY INFORMATION

Prevention of atherosclerotic arterial disease in patients with or without established cardiovascular disease requires control of all risk factors. No single risk factor, including cholesterol concentration, should be viewed in isolation.

consider all other risk factors, including hypertension and diabetic control (see appropriate separate guidelines)
antiplatelet drugs (aspirin and clopidogrel) are no longer recommended for primary prevention.

link to Simon Broome criteria

Patients with established vascular disease and/or ischaemic stroke** and/or diabetes

Patients with established occlusive arterial disease are at high risk and should be treated with a statin regardless of total cholesterol concentration, ie:

Previous MI	Pre- or post-CABG	Pre- or post-angiography
Definite angina*	Angiographic coronary artery disease	Definite peripheral artery disease*
Previous TIA or ischaemic stroke**

*’Definite’ indicates diagnosis confirmed by investigation or firm (not suspected) clinical diagnosis.
Patients aged over 40 years with diabetes but without established CVD should be treated with a statin regardless of total cholesterol concentration.
Patients under 40 years with diabetes should be considered for treatment with a statin if at least one of the following is present:

Retinopathy (requiring opthalmological treatment) – if maculopathy, treat with fibrate	Nephropathy, including persistent microalbuminuria	Hypertensive requiring antihypertensive therapy
Raised total cholesterol (>6 mmol/L)	Features of metabolic syndrome

Additional secondary prevention measures, eg antiplatelet therapy (Highland Formulary Antiplatelet section) should also be considered for all patients.

**SUPPLEMENTARY INFORMATION

Patients diagnosed with high risk acute coronary syndrome or ischaemic stroke will be treated with

ATORVASTATIN 80mg DAILY

(If not tolerated/side-effects try lower dose or different statin. Review dose annually.)

(Also see stroke guidance)

link to Simon Broome criteria

Monitoring requirements for statin efficacy

Statin interactions

Summary of common statin interactions (this list is not exhaustive; refer to BNF for full information on interactions)

Interacting drug	Simvastatin prescribing advice	Atorvastatin prescribing advice	Rosuvastatin prescribing advice*
Clarithromycin	Contra-indicated with simvastatin	Use lowest necessary dose of atorvastatin. Close monitoring advised for atorvastatin doses above 20mg daily. Avoid clarithromycin if possible.	No information of interaction
Erythromycin	Contra-indicated with simvastatin	Use lowest necessary dose of atorvastatin***	Possible reduction in rosuvastatin levels – not clinically relevant in short courses of erythromycin.
Verapamil Amiodarone Diltiazem	Do not exceed 20mg simvastatin daily	Use lowest necessary dose of atorvastatin (monitor lipid levels)***	No information of interaction
Amlodipine	Do not exceed 20mg simvastatin daily	No clinically significant interaction expected***	No information of interaction
Warfarin	Monitor INR	Monitor INR	Monitor INR
Ciclosporin	Contra-indicated with simvastatin	Do not exceed 10mg atorvastatin daily.*** Avoid if possible.	Contra-indicated with rosuvastatin
Grapefruit juice	Avoid grapefruit juice	Limit or avoid grapefruit juice intake	No information of interaction
HIV protease inhibitors**	Contra-indicated with simvastatin	Use lowest necessary dose of atorvastatin (monitor lipid levels). Consult manufacturers’ literature for maximum recommended doses. Avoid if possible.	Not recommended for combination use. Consult manufacturers’ literature for maximum recommended doses.
Itraconazole	Contra-indicated with simvastatin	Contra-indicated with atorvastatin	Increased level of rosuvastatin – not expected to be clinically significant.***
Posaconazole	Contra-indicated with simvastatin	Contra-indicated with atorvastatin	No information of interaction
Fluconazole	Use lowest necessary dose of simvastatin***	Use lowest necessary dose of atorvastatin***	No clinically significant interaction expected***
Miconazole oral gel	Contra-indicated with simvastatin	Contra-indicated with atorvastatin	No clinically significant interaction expected***
Sodium fusidate	Not recommended for combination use***	Not recommended for combination use***	Not recommended for combination use***
Ticagrelor	Do not exceed 40mg simvastatin daily	No clinically significant interaction expected***	No information of interaction

*If changing to rosuvastatin, start at 5 or 10mg daily and titrate up to 20mg daily if necessary (patients of Asian origin start at 5mg and do not exceed 20mg)

**See summary of product characteristics (SPC) for advice regarding specific drugs ***Monitor closely for signs of side-effects (eg myopathy, rhabdomyolysis)

Abbreviations

Abbreviation	Meaning
MI	Myocardial infarction
CABG	Coronary artery bypass graft
CVD	Cardiovascular disease
INR	International Normalised Ratio

Last reviewed: 13 June 2019

Next review: 13 June 2021

Author(s): Stroke Review Group

Version: 5

Approved By: TAM subgroup of ADTC

Document Id: TAM139

Guideline updates:

the Pink One