Statins

Question 1

What is the patient population indicated for Statins?

Answer 1

Guidelines
1. History of Clinical ASCVD

2. LDL >190 mg/dl -> High-intensity statins >50%
3. 40-75 yr old and with diabetes -> moderate statins 30-50%
4. 40-75 yr old and pooled cohort 10 yr-risk > 7.5%
   Risk assesment

Question 2

Primary Prevention
Assess ASCVD Risk in Age Groups

Answer 2

0-19y: Lifestyle change, consider statins if diagnosis of familial hypercholesterolemia

20-39y: consider statin if: family history of ASCVD or LDL >160

40-75y and LDL of 70-190 without diabetes: 10-year Risk assessment !!!!!!

Question 3

Primary Prevention in Patients in Statin Benefit Group

Answer 3

-LDL over 190: HIGH intense statin
-40-75 years and diabetes: moderate statins -> OR 10-year risk assessment to consider moderate or high intense statins
-Age over 75: clinical assessment

Question 4

Medication for 10-year risk categories

Answer 4

Low risk: <5% -> life style change

Borderline risk 5-7.5%: if a risk enhancer is present then moderate-intense therapy
Q: What are risk enhancers??? -> smoking, genetics

Intermediate risk 7.5 - 20%: moderate intense therapy

High risk >20%: high-intensity therapy

Question 5

How to work with patients if a risk decision is uncertain?

Answer 5

Run a Coronary Artery Calcium Score

Question 6

High-intensity Statins (>50%)

Answer 6

Atorvastatin 40-80 mg
Rosuvastatin 20-40 mg

Question 7

Moderate-intensity Statins (30-50%)

Answer 7

Atorvastatin 10-20 mg
Rosuvastatin 5- 10 mg
Simvastatin 20-40 mg
Pravastatin 40-80 mg

Lovastatin 40 mg
Fluvastatin XL 80 mg
Fluvastatin 40 mg BID
Pitavastatin 1-4 mg

Question 8

Light-intensity Statins (<30%)

Answer 8

Simvastatin 10 mg
Pravastatin 10-20 mg
Lovastatin 20 mg
Fluvastatin 20-40 mg

Question 9

When should statins be taken?

Answer 9

At night, bc more cholesterol is produced at night and the drug has a short half-life -> we want it to be as effective as possible

-for short-acting statins taking it at night reduces LDL by 10% more effectively than when it was taken in the morning

-for long-acting statins (atorvastatin, rosuvastatin, pitavastatin) the difference is not significant

Question 10

Adverse effects of Statins

Answer 10

-Statin-associated muscle symptoms (SAMS)
-can cause Diabetes mellitus
-Liver toxicity (rare)

Question 11

Should patients with liver damage be treated with Statins? !!!!

Answer 11

-patient with liver cirrhosis, or fatty liver disease and their liver enzymes are controlled

-the statins should be withheld if the liver enzymes are 3x the upper limit of normal (ULN)

f.e. normal: 30-50 -> anything above 149 would be counter indicative!!!

Question 12

Statins Half-life

Answer 12

Long-acting
Atorvastatin
Rosuvastatin
Pitavastatin

Short-acting:
Simvastaatin
Pravastatin
Lovastatin
Fluvastatin

Question 13

Metabolizing enzymes

Answer 13

CYP 3A4: Atorvastatin, Simvastatin, Lovastatin

CYP 2C9: Rosuvastatin, Pitavastatin, Fluvastatin

None: Pravastatin

Question 14

Common CYP3A4 inhibiting drugs interfering with statins

Answer 14

Amiodarone
Amlodipine
Diltiazem
Ranolazine
Verapamil

Question 15

Urinary excretion of Statins

Answer 15

pt with kidney injury: higher concentration of the drug -> higher risk for side effects -> choose statin with low urine excretion

Low Urine excretion:
Atorvastatin (2%)
Fluvastatin (5%)

Moderate:
Lovastatin (10%)
Rosuvastatin (10%)
Simvastatin (13%)

Higher Urine Excretion:
Pitavastatin (15%)
Pravastatin (20%)

Question 16

Hydrophilic VS Lipophilic

Answer 16

The more lipophilic the higher the risk for myalgia

-patients on lipophilic statins experiencing side effects should be switched to lipophilic statins to improve their experience with the drug
-some patients experience less symptoms with lipophilic statins

Lipophilic: Simvastatin, Lovastatin, Atorvastatin, Fluvastatin, Pitavastatin

Hydrophilic: Rosuvastatin, Pravastatin

Question 17

What are the risk factors for Statin-induced muscle injury?

Answer 17

-Age (>80y)
-Female
-Statin intensity
-low BMI
-chronic kidney disease
-low Vitamin D
-Drug-drug interactions: CYP 3A4 (increases serum concentration of statins);
Gemfibrozil: inhibits glucuronidation of statins -> less soluble -> less metabolized (excreted)
-Asian descent: due to polymorphism the AUC is twice as high

Question 18

Stages of Muscle Injury

Answer 18

Myalgia (in 5-20% cases)
CPK is <10x ULN

Myopathy, Myositis (0.5%)
CPK 3-10x ULN

Rhabdomyolysis (0.1%)
CPK >10x ULN + SCr elevated (acute renal damage due to nephrotoxic myoglobin coming into the kidney -> maybe urine color change)

Question 19

Drug changes in Muscle injury

Answer 19

Myalgia: reduce the dose or switch to hydrophilic

Myopathy: switch to hydrophilic, careful monitoring

Rhabdomyolysis: Stop statin

Question 20

Statin Intolerance Management

Answer 20

check risk factors, check CPK
-reduce dose
-change to hydrophilic statin
-alternate day dosing –> 3x week (only possible with long-acting statins: atorvastatin, rosuvastatin, pitavastatin)
-check vitamin D levels -> supplement with 50.000- 100.000 IU weekly