Prescribing Statins

Question 1

Statins have revolutionised the management of …

Answer 1

Statins have revolutionised the management of hypercholesterolaemia.

Question 2

Statins have become essential in the management of patients with, or at risk, of …

Answer 2

Statins have become essential in the management of patients with, or at risk, of cardiovascular disease including coronary artery disease (CAD), cerebrovascular disease and peripheral vascular disease (PVD).

Question 3

Indications of statins

Answer 3

Statins were primarily created to treat hypercholesterolaemia, which is an independent risk factor for cardiovascular disease.
Statins are indicated in both primary and secondary prevention of cardiovascular disease for many conditions.

Question 4

Primary prevention - statin QRISK

Answer 4

Cardiovascular risk assessment score ≥10%* and ≤ 84 years old (risk/benefit if >84)
Cardiovascular risk assessment score ≥10%* and type 2 diabetes mellitus (T2DM)
Type 1 diabetes mellitus (T1DM) and additional criteria (age, kidney disease, duration)
Chronic kidney disease (CKD)
Familial hypercholesterolaemia
*calculated using QRISK® score

Question 5

Secondary prevention- statin

Any patient with established cardiovascular disease

Answer 5

Myocardial infarction
Angina
Stroke or transient ischaemia attack (note caution below)
Peripheral arterial disease

Question 6

Mechanism of action - statin

Answer 6

The principle mechanism of statins is inhibition of 3-hydroxy-3-methylglutaryl- coenzyme A (HMG-CoA) reductase.

Question 7

Statin mechanism of action

Answer 7

HMG-CoA is an enzyme found in hepatocytes of the liver. It converts HMG-CoA into mevalonic acid, which is a cholesterol precursor. The reduction in hepatic cholesterol production leads to upregulation of hepatic LDL receptors that reduces circulating levels of LDL from the blood. The enzyme is most active at night leading to the nocturnal administration of statins.

Question 8

In addition, statins have other complex cholesterol-independent effects.

Answer 8

Statins can improve endothelial function, alter vascular smooth muscle proliferation, regulate cardiac hypertrophy, protect against ischaemic injury and exert anti-inflammatory properties. These cholesterol-independent effects support the targeted use of statins even with normal cholesterol levels.

Question 9

In the UK, the most well recognised statins available for clinical use include …

Answer 9

In the UK, the most well recognised statins available for clinical use include simvastatin, atorvastatin, rouvastatin and pravastatin.

Question 10

Atorvastatin is typically started at …-… mg daily for primary prevention. This can be increased if necessary (every four weeks) to a max of … mg (for example to lower cholesterol in familial hypercholesterolaemia).

Answer 10

Atorvastatin is typically started at 10-20 mg daily for primary prevention. This can be increased if necessary (every four weeks) to a max of 80 mg (for example to lower cholesterol in familial hypercholesterolaemia).

Question 11

In secondary prevention, high dose atorvastatin at … mg (max dose) is usually prescribed (unlicensed). However, in the presence of significant interactions (see below), this may need reducing.

Answer 11

In secondary prevention, high dose atorvastatin at 80 mg (max dose) is usually prescribed (unlicensed). However, in the presence of significant interactions (see below), this may need reducing.

Question 12

Statins should be used with caution in patients with, or at risk, of…

Answer 12

Statins should be used with caution in patients with, or at risk, of liver disease (i.e. NAFLD, high alcohol use, raised transaminases).

Question 13

It is important remember that statins are contraindicated in patients with …

Answer 13

It is important remember that statins are contraindicated in patients with severe liver disease (i.e. decompensated liver disease, acute liver failure).

Question 14

Other important cautions are untreated hypothyroidism, history of muscular disorders (see side-effects below), and stroke (hyperacute ischaemic and haemorrhagic). Stroke is a complex area and treatment should be guided by stroke specialists.
What medication

Answer 14

Other important cautions are untreated hypothyroidism, history of muscular disorders (see side-effects below), and stroke (hyperacute ischaemic and haemorrhagic). Stroke is a complex area and treatment should be guided by stroke specialists.
Statins

Question 15

The two important side-effects of statins are ….

Answer 15

The two important side-effects of statins are drug-induced liver injury (DILI) and myopathy.

Question 16

Statins are associated with a number of side-effects

Answer 16

Question 17

Drug-induced liver injury - statin

Answer 17

Statin therapy has been associated with development of varying degrees of severity of DILI. Patients with features of hepatotoxicity should have liver function tests checked and NICE recommend routine checks at 3 and 12 months. If transaminases are >3 time upper limit of normal, discontinue statin.

Question 18

Myopathy describes any type of muscle disease. Statin therapy is associated with a spectrum of skeletal muscle disorders. These disorders include: (4)

Answer 18

Myalgia (muscle ache, normal creatine kinase)
Myositis (muscle pain and weakness, inflammation, creatine kinase elevated)
Rhabdomyolysis (muscle pain and weakness, inflammation, muscle breakdown, creatine kinase markedly elevated).
Immune-mediate necrotising myopathy (muscle pain and weakness, immune-mediated inflammation, mild-to-moderate CK elevation)

Question 19

Rhabdomyolysis can be a life-threatening condition associated with …

Answer 19

Rhabdomyolysis can be a life-threatening condition associated with acute kidney injury, disseminated intravascular coagulation and multi-organ failure. In patients with muscle cramps and elevated creatine kinase (CK), statins should be discontinued. In mild episodes of myopathy, statins can be reintroduced at a lower dose but expert advice should be sought.

Question 20

Statins have several drug interactions due to their metabolism by the hepatic cytochrome … pathway.

Answer 20

Statins have several drug interactions due to their metabolism by the hepatic cytochrome P450 pathway.

Question 21

Statins have several drug interactions due to their metabolism by the hepatic cytochrome P450 pathway.
Classical interactions include…

Answer 21

Classical interactions include amiodarone and clarithromycin, which are enzyme inhibitors. Co-administration of an enzyme inhibitor leads to an increased risk of myopathy. The BNF should always be consulted for interactions.

Question 22

Pregnancy and statins

Answer 22

Statins are considered teratogenic and should be avoided.

Question 23

Pregnancy and monitoring

Statins are considered teratogenic and should be avoided.

Answer 23

Patients on statin therapy should have blood test monitoring. Baseline lipid profile, CK (if myopathy symptoms), U&Es, LFTs and TFTs should be checked. NICE subsequently recommend LFTs at 3 and 12 months and HbA1c in high-risk patients.

It is important to consider dose adjustment in renal impairment and the BNF or Renal drug handbook should be checked.

Question 24

Elevation of liver function tests >…x the upper limit of normal should lead to temporary or indefinite suspension of statin therapy.

Answer 24

Elevation of liver function tests >3x the upper limit of normal should lead to temporary or indefinite suspension of statin therapy.

Question 25

Which of the following best describes the mechanism of action of a statin?

A	Inhibition of cholesterol absorption
B	Bile acid sequestrant
C	Stimulate beta-oxidation of fatty acids
D	HMG-CoA reductase inhibitor
E	Reduces breakdown of adipose tissue

Answer 25

Statins are the main class of anti-lipid therapy that work by reducing cholesterol synthesis in the liver through inhibition of HMG-CoA reductase.

Question 26

Which of the following medications is considered teratogenic in pregnancy?
A	Amoxicillin
B	Atorvastatin
C	Methyldopa
D	Enoxaparin
E	Folic acid

Answer 26

Statins are considered teratogenic in pregnancy and should be avoided.
The risk of statins in pregnancy has mainly been derived from animal studies with some conflicting data.

Question 27

A 72 year old gentleman is admitted to accident and emergency with severe muscle pains following initiation of simvastatin by his GP 3 weeks ago. He is noted to have reduced urine output and on urgent blood tests he has a raised serum creatinine with mild metabolic acidosis. He is given intravenous fluids and his simvastatin has been held.

What is the single most appropriate blood test to support the suspected diagnosis?

A	Full blood count (FBC)
B	Creatine kinase (CK)
C	Thyroid function tests (TFTs)
D	Glycosylated haemoglobin (HbA1c)
E	Urea and electrolytes (U&Es)

Answer 27

A CK is the most appropriate test for the diagnosis of statin-induced rhabdomyolysis.

This patient is suffering from statin-induced rhabdomyolysis, which is a potentially life-threatening diagnosis. Statin-induced rhabdomyolysis is thankfully rare occurring in less than 1 in 100,000 patients treated with the drug. The detection of a markedly elevated CK, which is reflective of skeletal muscle breakdown, is the key diagnostic test. However, the syndrome is defined by evidence of myoglobinuria from muscle breakdown, and acute tubular necrosis leading to acute kidney injury. The condition is usually transient and will lead to recovery, but some patients may require renal support.

Other muscular disorders associated with statin therapy include myalgia (muscular pain, mild CK elevations), statin-induced toxic myopathy (muscular pain and weakness, mild-to-moderate CK elevations, non-immune mediated) and immune-mediated necrotising myopathy (muscle pain and weakness, mild-to-moderate CK elevations, requires biopsy confirmation and immunosuppression).

Question 28

Which of the following conditions would you expect the creatine kinase (CK) to be normal?

A	Myalgia
B	Myositis
C	Rhabdomyolysis
D	Immune-mediate necrotising myopathy
E	Duchenne muscular dystrophy

Answer 28

The development of myalgia (muscle ache/pain) is common with statin therapy, but would not lead to CK elevations as there is no muscle damage.

Duchenne muscular dystrophy is a rare X-linked inherited condition, which results in marked muscle weakness and wasting in young boys. It may be suspected in a young boy with muscle weakness and an elevated CK. The condition can affect girls in rare instances.

The rest are all complications of statin therapy, which are associated with CK elevations.

Question 29

synthesis?

A	Cerebral cortex
B	Lungs
C	Spleen
D	Liver
E	Ovaries

Answer 29

Hepatocytes within the liver express the enzyme HMG-CoA reductase, which is critical in the synthesis of cholesterol.

Question 30

Question 7.
Which of the following medications has a potentially dangerous interaction with simvastatin?

A	Levothyroxine
B	Amiodarone
C	Amlodipine
D	Quinine
E	Ramipril

Answer 30

Amiodarone is an inhibitor of the cytochrome P450 enzyme family situated in the liver.
When amiodarone is co-prescribed with simvastatin, or other statins, it can lead to elevated levels of simvastatin and increases the risk of rhabdomyolysis. Amlodipine should be used with caution in patients on simvastatin. Other enzyme inhibitors that may cause dangerous interactions include bezafibrate, clarithromycin, ciclosporin, itraconazole and grapefruit juice (in excess).

Question 31

When amiodarone is co-prescribed with simvastatin, or other statins, it can lead to elevated levels of simvastatin and increases the risk of … Amlodipine should be used with caution in patients on simvastatin. Other enzyme inhibitors that may cause dangerous interactions include bezafibrate, clarithromycin, ciclosporin, itraconazole and ..juice (in excess).

Answer 31

When amiodarone is co-prescribed with simvastatin, or other statins, it can lead to elevated levels of simvastatin and increases the risk of rhabdomyolysis. Amlodipine should be used with caution in patients on simvastatin. Other enzyme inhibitors that may cause dangerous interactions include bezafibrate, clarithromycin, ciclosporin, itraconazole and grapefruit juice (in excess).

Question 32

Statins are generally considered contraindicated in which condition?

A	Stroke
B	Myocardial infarction
C	Chronic kidney disease
D	Decompensated cirrhosis
E	Peripheral vascular disease

Answer 32

Statins are contraindicated in patients with decompensated cirrhosis or acute liver failure (i.e. advanced liver disease).
Statins should be used with caution in patients with, or suspected, liver disease. Statins form a key medication in the mitigation of stroke risk, but should be used with caution in patients with hyperacute stroke or history of intra-cerebral haemorrhage. The prescription of statins in this context should be guided by specialists.

Question 33

Statins are an important drug in the treatment of familial hypercholesterolaemia.

What is the predominant mode of inheritance in familial hypercholesterolaemia?

A	Autosomal dominant
B	Autosomal recessive
C	X-linked dominant
D	X-linked recessive
E	Mitochondrial

Answer 33

Familial hypercholesterolaemia is predominantly inherited in an autosomal dominant pattern due to mutation in the LDLR gene.
The LDLR gene encodes the low-density lipoprotein receptor, which is important in removing LDL cholesterol from the blood. Familial hypercholesterolaemia should be suspected in any patient with a total cholesterol level > 7.5 mmol/L or a personal or family history of early onset coronary artery disease (before 60 years old).

Question 34

The LDLR gene encodes the low-density lipoprotein receptor, which is important in removing LDL cholesterol from the blood.

Familial hypercholesterolaemia should be suspected in any patient with a total cholesterol level > … mmol/L or a personal or family history of early onset coronary artery disease (before 60 years old).

Answer 34

The LDLR gene encodes the low-density lipoprotein receptor, which is important in removing LDL cholesterol from the blood. Familial hypercholesterolaemia should be suspected in any patient with a total cholesterol level > 7.5 mmol/L or a personal or family history of early onset coronary artery disease (before 60 years old).

Question 35

A 65 year old male is recently discharged from hospital following an ST-elevation myocardial infarction (STEMI), which was treated with primary percutaneous coronary intervention (PCI). His only background history is hypertension. His renal function during admission was stable and he has no known drug allergies. The cardiology team initiate him on atorvastatin.

What would be the correct dose of atorvastatin in this case?

A	10 mg
B	20 mg
C	40 mg
D	80 mg
E	160 mg

Answer 35

Patients requiring statin therapy for secondary prevention of cardiovascular disease (e.g. post myocardial infarction) should be treated with high-dose statins as tolerated.
When prescribing a statin, any significant interaction, dose-reduction requirement (i.e. chronic kidney disease) or contraindications should be determined before prescribing.

Question 36

Patients requiring statin therapy for secondary prevention of cardiovascular disease (e.g. post myocardial infarction) should be treated with …-dose statins as tolerated.
When prescribing a statin, any significant interaction, dose-reduction requirement (i.e. chronic kidney disease) or contraindications should be determined before prescribing.

Answer 36

Patients requiring statin therapy for secondary prevention of cardiovascular disease (e.g. post myocardial infarction) should be treated with high-dose statins as tolerated.
When prescribing a statin, any significant interaction, dose-reduction requirement (i.e. chronic kidney disease) or contraindications should be determined before prescribing.