15/16 - Lipid Drugs

Question 1

Primary Prevention

Treatment Decisions

Answer 1

Table will be given on EXAM

Patients with:
BODERLINE / INTERMEDIATE RISK
will be based on:
ASCVD RISK ENHANCERS
also given on the exam

• **Know METABOLIC SYNDROME is one of them**
• *coronary artery calcium = CAC**
• CONTROVERSIAL EVIDENCE*

Question 2

Cardiovascular Risk Factors

NON-MODIFIABLE

Answer 2

↑Age

MALE

RACE

Family History of:

• *Premature CHD** in 1st degree Relative
• *Males < 55yr** // Females < 65yr

Question 3

Fibrates

Drugs & Uses

Answer 3

Gemfibrozil / Fenofibrate / Fenofibric Acid

1st line for SEVERE HYPERTG’s
TG > 500mg/dL
first rule out secondary causes, can cause PANCREATITIS

TG: ↓ 20-50%
LDL: ↓ 5-20%
May increase in patients with high TG
HDL: ↑ 10-20%

Question 4

Bile Acid Sequestrants

Drugs / Use?

Answer 4

Cholestyramine / Colestipol / Colesevalam
take b4 heaviest meals

can INCREASE TG’s** & **no ASCVD outcomes

Weak recommendation for add on therapy if:

• *If TG < 300mg/dL**
• *LDL >190 mg/dL** and < 50% LDL lowering while on statin and ezetimibe

Question 5

PCSK9 INHIBITORS
Evolocumab (Repatha) / Alirocumab (Praluent)

ADR / CONCERNS

Answer 5

NEUROCOGNITIVE EFFECTS
Though seen that:
Risk does NOT outweight benefit of additional CV risk reduction

benefit in severe LDL>190 patients?

PRICE

Question 6

High Risk Conditions

• *Very High Risk Clinical ASCVD**
• *1 Major ASCVD Event + Multiple High Risk Conditions**

Answer 6

> 65 y/o - Currently SMOKING

Diabetes / HTN / CKD

• *Persistant LDL-C elevation**
• *>** 100 despite max statin + ezetimibe

Heterozygous FC
familial hypercholesterolemia

History of:

• *CABG** or PCI
• *Congestive HF**

Question 7

Clinical ASCVD
What classifies a patient to be
VERY HIGH RISK ASCVD?

Answer 7

MULTIPLE Major ASCVD Events

OR

1 Major ASCVD Event** + **Multiple High-Risk Conditions

Age does NOT matter

Major ASCVD Events
Recent ACS (<12mo) - H/O MI - H/O Ischemic Stroke
Symptomatic PAD

Question 8

MONITORING
STATIN THERAPY

Answer 8

4-12 Weeks
after initiation or dose adjustment

• *3-12 MONTHS after**
• clinically every 12 months*

Why?
monitor expected response & adherence

Question 9

Fibrates
Gemfibrozil / Fenofibrate / Fenofibric Acid

Contraindications / ADR / DI

Answer 9

CI:
Hepatic / Renal dysfunction
GALLBLADDER DISEASE–>can cause PANCREATITIS

GI Side Effects

DI:
STATINS –> can INCREASE RISK of MYOPATHY
need to monitor closesly

Question 10

Treatment of Muscle Symptoms
STATINS

Mild-Moderate

Answer 10

Evaluate for other conditions that may increase risk:
Renal / Hepatic dysfunction
Rheumatologic Disorders
Vitamin D deficiency
Primary muscle diseaes

DC STATIN
or use LOWER DOSES

Possibly –> HYDROPHILIC STATIN INSTEAD
Rosuvastatin / Pravastatin / Fluvastatin

Question 11

PCSK9 INHIBITORS
Evolocumab (Repatha) / Alirocumab (Praluent)

Uses / Indications

Answer 11

Increased with STATIN COMBINATION

Approximately 60% further LDL reduction

Significant reduction in primary composite endpoint

• *FOURIER** results driven by reduction in:
• *stroke, non-fatal MI, and coronary revascularizations**

Question 12

Cardiovascular Risk Factors

MODIFIABLE

Answer 12

SMOKING

• *HTN**:
• *> 130/80** or on meds

Obesity / Diabetes / Poor Diet / Physical Inactivity

↑LDL

Question 13

When do we prefer to take STATINS?

Answer 13

EVENING
due to nighttime upturn in endogenous cholesterol synthesis

except for:
atorvastatin / rosuvastatin / pitavastatin

due to long half lives

Question 14

Clinical ASCVD

• *Treatment for:**
• *Max Tolerated statin** + LDL > 70 mg/dL

Answer 14

add:
EZETIMIBE

Question 15

Bile Acid Sequestrants
Cholestyramine / Colestipol / Colesevalam

Contraindications / ADR / DI’s

Answer 15

Contraindicated:
Fasting TG > 300mg/dL
biliary or bowel obstruction

ADR:
GI issues, not absorbed from GI tract

DI:
binds NEGATIVELY charged drugs –> ↓Absorption
warfarin / thiazide / beta blockers
seperation of doses

Question 16

Major ASCVD Events

4

Answer 16

Recent ACS
within 12 months

• *History of MI**
• other than recent ACS event above*

History of ISCHEMIC STROKE

Symptomatic PAD

• *>1** of these OR 1 of these + High Risk Conditions
• *Very High Risk Clinical ACSVD**

Question 17

Clinical ASCVD

• *Treatment for:**
• *Very High Risk** with Statin & Ezetimibe
• *LDL > 70**

Answer 17

Max Statin + Ezetimibe

ADD:
PCSK9 INHIBITOR

Question 18

Which drug has the special indication for:

HeFH
Heterozygous Familial HyperCholesterolemia

Answer 18

PCSK9 INHIBITORS
Evolocumab (Repatha) / Alirocumab (Praluent)

Question 19

Ezetimibe = Zetia

Effects & MoA

Answer 19

Cholesterol Absorption Inhibitor
selectively inhibits absorption of dietary & biliary choleseterol
@brush border of intestine

LDL: ↓ 18-22%
HDL: ↑ 0-2%
TG: ↓ 0-5%

Combination with Statin –> ↓Risk of CV events
IMPROVE-IT Trial

Question 20

When would we consider:
MODERATE INTENSITY STATIN >High Intensity?

Answer 20

• *Qualify for HIGH-intensity but have:**
• *>** 75 y/o

Multiple or serious comorbidities:
Renal or Hepatic Impairment

H/O of:
previous STATIN intolerance or Muscle disorders

ALT Elevations > 3x ULN

Drug interations

Question 21

Omega-3 Fatty Acids​

ADR / CI / DI

Answer 21

ADR:
Dyspepsia / FISH TASTE

DI:
ANTIPLATELET ACTIVITY
can increase risk of bleeding with AntiCoag meds

Question 22

Statin

Effects / Uses

Answer 22

Most Potent LDL-Lowering Agents

LDL: ↓ 18-55%

HDL: ↑5-15%

TG: ↓ 7-30%

Significantly Reduce:
CHD Death / Non-Fatal MI / Strokes
Revascularization Procedures
Total Mortality

Question 23

RHABDOMYOLYIS

Statin ADR / Monitoring

Answer 23

CK > 10x ULN** + **ELEVATED SCr

Muscle breakdown –> myoglobinuria

Reoutine monitoring of CK is NOT NECESSARY
only check if unexplained muscle pain / tenderness / weakness
increased risk in:
>65 y/o
Renal Dysfunction
Check @ Baseline only

Question 24

PCSK9 INHIBITORS
Evolocumab (Repatha) / Alirocumab (Praluent)

MoA

Answer 24

• *Indirectly decreases LDL levels** by
• *regulating available LDL receptors**

•Binds to PCSK9

•Prevents PCSK9 from binding to LDL-R

↑hepatocellular LDL-R

•Decreases circulating LDL

Question 25

**_Diabetes**_ & _**Age 40-75_** **When to ADD EZETIMIBE?**

Answer 25

High Intensity Statin + Ezetimibe for Diabetes if: ## Footnote **_10 year ASCVD risk \> 20%_**

Question 26

**_Primary Prevention_** **ASCVD Risk Enhancer:** **METABOLIC SYNDROME**

Answer 26

**_\>_** **3** **Criteria = Metabolic Syndrome** "WTH-HtG" **_Waist Circumference_** \>40in males // \>35in Females **_↑TG's_** meds or \>175 **_↑Fasting Blood Glucose_** meds or \>100 **_HyperTension_** meds or \>130/85 **_↓__HDL-C_** meds or \<40 males // \<50 females

Question 27

**_Nicotinic Acid / Niacin_** ## Footnote **USES**

Answer 27

*previously used to:* **↓ TG and ↑ HDL​** BUT: **no longer used due to _INCREASED ISCHEMIC STROKES_** was the **best drug to ↑ HDL​** ADR: * *liver / PUD** * *alcohol / FLUSHING**

Question 28

**_Therapeutic Lifestyle Changes_**

Answer 28

**_DIET_** **_Physical Activity_** Aerobic exercise = **3-4x week** @**40min per session** **_SMOKING CESSATION_** **_WEIGHT MANAGEMENT_**

Question 29

**Statin ADRs**

Answer 29

**_MYALGIA_** Muscle pain / tenderness / weakness **routine CK monitoring is NOT necessary** **HA / Fatigue / GI upset** **_Elevated LFTs_** rare, **check LFT @ baseline** **Cognitive Impairment** **↑****HbA1c**and ↑**Fasting Glucose** ASCVD risk benefit OUTWEIGHT the risk

Question 30

**_Diabetes**_ & _**Age 40-75_** ## Footnote **Treatment?**

Answer 30

***_at LEAST_*** **_MODERATE INTENSITY STATIN_** ↓ LDL 30% to \< 50% 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 2 – 4 mg

Question 31

**CONTRAINDICATIONS** **Statins** **Specific Drugs?**

Answer 31

* *_PREGNANCY_** * *Lactation** **ACTIVE LIVER DISEASE** * *_SIMVASTATIN_** * *10 mg** --\> **Verapamil / Diltiazem** **20mg --\> Amiodarone / Amlodipine / Ranolazine** ↑Chance of Myalgas

Question 32

**_Omega-3 Fatty Acids_** **USES / MoA**

Answer 32

* *Add on Therapy for** * *_TG CONTROL_** * if intolerant to FIBRATES* * no LDL / HDL effects,* * *_TG: ↓ 14-40%​_** MoA: **↓hepatic VLDL production ↓# of FFA available for TG synthesis**

Question 33

**_Diabetes**_ & _**Age 40-75_** **When to give HIGH INTENSITY STATIN?** Atorvastatin 40 / 80 Rosuvastatin 20 / 40

Answer 33

**_Multiple ASCVD Risk Factors_** OR **_RISK MODIFIERS_** **Long duration of DM** (**\> 10 yrs** for DM2; \> 20 yrs for DM1) **Albuminuria \> 30 mcg** **eGFR \< 60** **Retinopathy / Neuropathy ABI \< 0.9**

Question 34

**Treatment of Muscle Symptoms STATINS** **_SEVERE_**

Answer 34

**Severe muscle symptoms** or **Fatigue** that are ***_UNEXPLAINED_*** **_DC STATIN_ Evaluate CK / SCr / Urinalysis for myoglobinuria** **Rhabdo = all 3** * *Myopathy = CK \>10x ULN + Myalgia** * DOSE dependent*

Question 35

* *_Severe HYPERcholesterolemia_** * *LDL _\>_** **190** ## Footnote **When to add EZETIMIBE?**

Answer 35

**\< 50% Reduction with Statin**

Question 36

**Statin's** **MoA**

Answer 36

Competitive inhibitor of: **_HMG CoA Reductase_** rate-limiting step of cholesterol syntehsis ↓**Hepatocellular Cholesterol** --\> **↑LDL Receptors** VV **↑LDL Clearance** _Non-Lipid Effects:_ Restore **Endothelial Function** ↓**Inflammation /** ↓**Ischemic Episodes Stabilize Vunrable Plaques**

Question 37

**_Clinical ASCVD_** * *Treatment for:** * *Very High Risk** OR **_\<_** **75 y/o** MULTIPLE Major ASCVD Events OR 1 Major ASCVD Event + Multiple High-Risk Conditions

Answer 37

**HIGH INTENSITY STATIN** Atorvastatin 40 / 80 Rosuvastatin 20 / 40 Goal: ↓**LDL** **_\>_** **50%**

Question 38

**When can we NOT use LDL levels?**

Answer 38

**TG \> 400** we can NOT use calculated LDL levels **LDL** **_\>_** **190** = **Very High** **TG \> 500 = Very High**

Question 39

**_Myopathy_** **Statin ADR / Monitoring**

Answer 39

**_MYALGIA**_ + _**CK \> 10x ULN_** **Dose Dependent** Reoutine monitoring of CK is ***_NOT NECESSARY_*** only check if **unexplained muscle pain / tenderness / weakness** increased risk in: **\>65 y/o Renal Dysfunction** **Check @ Baseline only**

Question 40

**_Low Intensity Statins_**

Answer 40

**↓ LDL \< 30%** **Pravastatin 10 / 20** **Lovastatin 20** * *_Simvastatin 10mg_** * 20 is moderate* Flustatin 20 / 40 Pitavastatin 1mg **_Only 10mg or 20mg Doses except for:_** **Atorvastatin / Rosuvastatin / Simvastatin 20mg** All are either moderate or high intensity

Question 41

**What is CLINICAL ASCVD?**

Answer 41

**AtheroSclerotic CardioVascular Disease** _someone who has or has had:_ **_ACS**_ / _**TIA**_ / _**Stroke**_ / _**PAD_** History of: * *_MI_** = Myocardial infarction * *_UA_** = Stable or unstable angina _ALL FROM ATHEROSCLEROTIC ORIGIN_

Question 42

**_HIGH-Intensity Statins_**

Answer 42

**↓ LDL _\>_ 50%** **Atorvastatin 40 / 80** **Rosuvastatin 20 / 40**

Question 43

* *_Severe HYPERcholesterolemia_** * *LDL _\>_** **190** ## Footnote **When to add PCSK9 Inhibitor?**

Answer 43

On **Statin + Ezetimibe** & **LDL _\>_** **130**

Question 44

**Ezetimibe = Zetia** **CI / ADR / DI**

Answer 44

Contraindicated in: * *Active Liver Disease** or **unexplained ↑LFT** * *Pregnancy & Lactation** ADR: **Diarrhea / Ab Pain** DI: **_FIBRATES_** --\> ↑**Liver Enzymes** / ↑**cholecstectomy** **_CHOLESTYRAMINE_** = ↓Ezetimibe AUC

Question 45

**What is considered PREMATURE ASCVD?** **ASCVD Risk Factor if First Degree Relative has...**

Answer 45

**Males \< 55yr** **Females \< 65yr**