• Home
• Protocols
• Cardiovascular
• Lipids

Hyperlipidaemia

• FATS3 - A district wide strategy for the use of cholesterol lowering drugs in Newcastle and North Tyneside
• FATS3 – additional guidance

---

Guidelines for the management of serum cholesterol in patients with established coronary artery disease

Footnotes

1. Evidence is for patients < 70 years. Discretion for patients> 70 years.
2. The recent SMAC advice on use of statins distinguishes between a level for patients post MI (4.8mmolll) and for other symptomatic CHD (5.5mmolll). We have chosen a level for all secondary prevention of 5.0 mmol/l aiming to include more patients in a regime for secondary prevention and for ease of use.
3. Great care in initiating thyroxine in hypothyroid patients. Use small initial dose and careful titration to avoid exacerbation of ischaemia.
4. Consider referral to dietician.
5. This guideline is equally applicable for patients with non-coronary atherosclerotic disease.

---

• Statin manager
• Use of statins
• Practice formulary: statins
• Testing pitfalls and summary of guidance in lipid management
• Considering statins - sharing risk

---

Therapeutic considerations for use of statins

CAUTIONS	History of liver disease or with a high alcohol intake (use should be avoided in active liver disease). Liver-function tests should be carried out before and within 1 - 3 months of starting treatment and thereafter at intervals of 6 months for 1 year, unless indicated sooner by symptoms or signs suggestive of hepatotoxicity. Treatment should be discontinued if serum transaminase concentration rises to, and persists at, 3 times the upper limit of the reference range. Patients should be advised to report unexplained muscle pain.
CONTRA-INDICATIONS	Active liver disease Pregnancy (adequate contraception should be ensured during treatment and for 1 month afterwards) Breast-feeding
SIDE-EFFECTS	Reversible myositis Headache Altered liver-function tests Gastro-intestinal effects including abdominal pain, nausea and vomiting.
MUSCLE EFFECTS	Myalgia, myositis and myopathy have been reported with the statins; if the creatine kinase concentration is markedly elevated (> 10 times upper limit of normal), and myopathy is suspected or diagnosed, treatment should be discontinued. There is an increased incidence of myopathy if the statins are given with a fibrate lipid-lowering doses of nicotinic acid immunosuppressants such as Ciclosporin; Close monitoring of liver function and, if symptomatic, of creatine kinase is required in patients receiving these drugs. Rhabdomyolysis with acute renal impairment secondary to myoglobinuria has also been reported.
INVESTIGATIONS	Liver-function tests should be carried out before and within 1 - 3 months of starting treatment and thereafter at intervals of 6 months for 1 year, unless indicated sooner by symptoms or signs suggestive of hepatotoxicity. Closer monitoring of patients taking a fibrate lipid-lowering doses of nicotinic acid immunosuppressants such as Ciclosporin;
COUNSELLING	Advise patient to report promptly unexplained muscle pain, tenderness, weakness.

Explanatory text on guidelines for the management of serum cholesterol

By mid 1994 a number of secondary prevention trials using HMG-CoA reductase inhibitors in post AMI patients had been published. In general these studies showed that for each 10% reduction in cholesterol a 20% reduction in morbidity and mortality is obtained. The same was shown by the older "non-statin ¹⁰ trials. The Scandinavian Simvastatin Survival Study (4S) trial was the first single trial to show that cholesterol reduction in post AMI patients will reduce morbidity and mortality (including total mortality).

"4S" Study (1)

Brief synopsis of "45" trial

• Males and females, 35 - 70 years (average 60 years) 80% had previous AMI and the other 20% angina.
• Initial total cholesterol >5.5 mmol/L, randomised to simvastatin 20 mg od po, or placebo.
• After a follow up of 5.4 years, total cholesterol was reduced by 25% and total mortality reduced by 30%.
• In addition, major coronary events (defined as coronary death or any non-fatal AMI or resuscitation from cardiac arrest) were reduced by 34%.
• The risk of developing unstable angina, need for revascularisation, having a TIA or CVA were also reduced by about 30%.
• There were no increases in deaths from suicide, cancer or accidents. 6% withdrew from therapy in both treatment and placebo groups (presumed side effects).

"Care" Trial (2)

The CARE study progressed understanding by addressing the issue of secondary prevention as it applies to the majority of patients with average (not high) cholesterol values.

Brief synopsis of "CARE" study

• Survivors of acute MI with total cholesterol, 6.2 (and LDL 3.0-4.5).
• Pravastatin 4Omg od po versus placebo.
• 4159 males and females whose cholesterol levels were similar to the general population (the high and low cholesterol patients were removed from the study).
• A 20% reduction in total cholesterol occurred.
• A significant reduction (p=0.002) in CAD fatality and non-fatal MI were observed over five years.
• There was also a significant reduction in PTCA and CABG rates in treated group, and a significant reduction in CVA.

"ASPIRE" study (3)

Brief synopsis of ASPIRE study:

• The objective was to measure the potential for secondary prevention in CAD in the UK (which was found to be considerable).
• 2583 CAD patients surveyed. Found very poor rates of success in secondary prevention. For example >75% had cholesterol >5.2 at follow-up, up to 27% still smoked, 75% remained overweight, up to 25% remained hypertensive, only 30% were on a beta blocker, and up to 20% were not on aspirin.

Comments

• The guidelines for the management of serum cholesterol presented here are straightforward. Patients with known coronary disease are targeted.
• Measures to reduce total cholesterol to less than 5.Ommol/L are mandatory in every patient with coronary disease.

References

1. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with curonary heart disease. Lancet 1994, 344, 1383 - 9.
2. Frank M et al. The Effect of Pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. New Eng J Med 1996, 335, 1001-1009.
3. A British Cardiac Society survey of the potential for the secondary prevention of coronary disease: ASPIRE (Action on secondary prevention through intervention to reduce events) principal results. ASPIRE Steering Group. Heart 1996, 75 (4), 334 - 342.

---

Testing pitfalls and summary of guidance in lipid management

Testing lipids

How often should patients' lipids be tested after starting lipid lowering treatment?

• 8 (±4) weeks after starting drug treatment
• 8 (±4) weekly after adjustments to treatment until within the target range

How often should cholesterol or lipids be tested once a patient has reached target or optimal cholesterol?

• Annually (unless there is a specific reason for more frequent reviews)

How often should cholesterol or lipids be tested when assessing a patient's coronary risk?

Before starting lipid lowering drug treatment:

• At least two measurements taken 1-12 weeks before starting drug treatment

In patients taking lipid lowering drugs:

• In secondary prevention not at treatment threshold: annually
• Higher risk primary prevention not at treatment threshold: every 1 or 2 years
• In lower risk primary prevention: every 5 years

Liver enzymes and statins

How often should liver enzymes be routinely measured in patients taking statins?

Measure alanine aminotransferase:

• Before treatment with a statin
• 8 weeks after starting a statin or after any dose increase
• Annually thereafter if liver enzymes are < 3xupper limit of normal

What if liver enzymes become raised in a person taking a statin?

If 3xupper limit of normal:

• Continue statin
• Recheck liver enzymes in 4-6 weeks
• No extra monitoring required unless values rising

If 3xupper limit of normal (depending on magnitude of rise):

• Stop statin or reduce dose, recheck liver enzymes within 4-6 weeks
• Cautious reintroduction of statin may be considered (eg, lower dose)

How often should creatine kinase be measured in patients taking statins?

Pre-treatment

• Before starting treatment with a statin
• If baseline creatine kinase level > 5 times ULN, do not start statin

Monitoring

Risk factors for myopathy absent:

• Routine monitoring of creatine kinase is not necessary
• Check creatine kinase if patient develops myalgia Risk factors for myopathy present:
• Balance risk/benefit of treatment with a statin
• If a statin is prescribed: check creatine kinase within 8 weeks of commencing statin, after any dosage increase or if patient develops myalgia

What if creatine kinase becomes raised in a person taking a statin?

If 5xupper limit of normal:

• Stop treatment, check renal function and monitor creatine kinase fortnightly
• Consider secondary causes of myopathy if creatine kinase remains elevated If 5xupper limit of normal:
• If no muscle symptoms, continue statin (patients should be alerted to report symptoms; consider further checks of creatine kinase)
• If muscle symptoms, monitor symptoms and creatine kinase regularly if creatine kinase continues to rise

Secondary hyperlipidaemia and hypertriglyceridaemia

When should I screen for secondary hyperlipidaemia and what investigations are required?

In all patients in whom lipid lowering therapy is being considered. The investigations are:

• Dietary, alcohol, and drug history
• Urine dipstick testing for protein
• Laboratory or point of care blood glucose
• Renal function
• Liver enzymes (transaminase)
• Thyroid stimulating hormone (if the total cholesterol is > 8 mmol/l, unless thyroid disease is suspected clinically)

When should I measure triglycerides at the same time as I measure cholesterol?

• In all people being assessed for risk of cardiovascular disease
• In all people being considered for lipid lowering treatment
• In monitoring, if the first triglyceride level was > 2 mmol/l

What triglyceride levels are associated with a risk of pancreatitis and require treatment on this basis?

Serum triglycerides of:

• 5 mmol/l carry a probable increased risk of pancreatitis
• 10 mmol/l carry a high risk of pancreatitis
• 20 mmol/l carry a very high risk of pancreatitis Persistent values over 5 mmol/l justify treatment

Testing pitfalls and summary of guidance in lipid management

• Brad Cheek: last updated Dec 2006
• Home
• Doctors
• Training
• IT
• Links
• Latest
• Search