3.4 Only Green Star slides info

What is the goal of treating dyslipidemia?

To prevent a clinical outcome (ASCVD event)

_________ are used as a surrogate to predict clinical outcomes

Lipid parameters

What are the components of the ASCVD calculator?

1. Age

2. HDL

3. TC

4. SBP

5. Gender

6. Current treatment for HTN

7. Diabetes

8. Race (white, African American, other)

9. Smoking status

All patients should be assessed for _________ regardless of decision to start drug therapy

improvements in diet and lifestyle

Which are the targeted lifestyle interventions?

1. Exercise

2. Smoking cessation

3. Diet (Mediterranean, fruits & veggies)

4. Weight loss

5. Alcohol

What is the recommended amount of exercise when talking about lifestyle interventions?

30-60 minutes per day, for 5 or more days per week

What is the recommended amount of alcohol when talking about lifestyle interventions?

Women: at most 1 drink a day

Men:1-2 drink per day

Abstinence may be more beneficial

Guidelines determine that there are 4 Statin Benefit groups, which are they and what kind of prevention?

Group 1 : Secondary Prevention

Groups 2-4: Primary Prevention

Group 1 - Clinical ASCVD (Atherosclerotic Cardiovascular Disease) which includes individuals with

Acute coronary syndromes, or

A history of myocardial infarction,

Stable or unstable angina,

Coronary or other arterial revascularization,

Stroke, TIA (transient ischemic attack), or

Peripheral arterial disease

Group 2 - Primary Hypercholesterolemia which includes Individuals with:

Primary elevations of LDL-C ≥190 mg/dL

Group 3 - Diabetes Mellitus (Age 40-75 years), which includes individuals aged 40-75 years with:

Diabetes, and LDL-C 70-189 mg/dL without clinical ASCVD

Group 4 - Primary Prevention (No Diabetes or ASCVD) which includes Individuals without clinical ASCVD or diabetes, who are:

40-75 years of age, with LDL-C 70-189 mg/dL, and Estimated 10-year ASCVD risk of 7.5% or higher

Should we determine risk factors (or/+ ASCVD risk calculator) for Group 1 individuals?

No

Group 1 can be subdivided into 2 groups, Very high risk and NOT very high risk. What do these mean?

• VHR- Multiple major ASCVD events OR One Major ASCVD event and 2+ high-risk conditions

• NVHR- One Major ASCVD event and 1 or fewer high-risk conditions

For Group 1 VHR patients should be started on _____, while NOT VHR patients should be started on ________ if < 75 years

- High intensity statin (max tolerated dose)

- High intensity statin

When can ADD-ON therapy be considered for Group 1 VHR patients?

If LDL remains > 55 mg/dL OR < 50% reduction consider add-on with:

1. ezetimibe and/or PCSK9

OR

2. bempedoic acid or inclisiran

When can ADD-ON therapy be considered for Group 1 NOT VHR patients?

High intensity statin if < 75 years; can consider add-on therapy if LDL remains > 70 mg/dL / < 50% reduction

If > 75 years less clear; any statin better than none; high intensity preferred if can be tolerated

Which are considered Major ASCVD events that put a patient in the category of Very High-Risk* of Future ASCVD Events?

- Recent ACS (within the past 12 months)

- History of MI (other than the recent ACS event listed above)

- History of ischemic stroke

- Symptomatic peripheral arterial disease (history of claudication with ABI

Which are considered High risk conditions?

- Age ≥ 65 years

- Heterozygous familial hypercholesterolemia

- History of prior coronary artery bypass surgery or percutaneous coronary intervention (PCI) outside of the major ASCVD event(s)

- Diabetes mellitus

- Hypertension

- CKD (eGFR 15-59 mL/min/1.73 m²)

- Current smoking

- Persistently elevated LDL-C (LDL-C ≥100 mg/dL [≥2.6 mmol/L]) despite maximally tolerated statin therapy and ezetimibe

- History of congestive heart failure

The _______ showed that adding Vascepa (2 g BID, EPA-only) to statin therapy in patients with _____ and ______ reduced major CV events from 22% to 17.2% (ARD 4.8%, NNT 21 over 4.9 years).

- REDUCE-IT trial

- ASCVD or diabetes + 1 risk factor and TG 135-499 mg/dL

Vascepa provides________ as an add-on to statins, with lower cost than ______ but higher than ____, though its comparative efficacy remains unclear and guidelines do not yet define its role.

- proven ASCVD risk-reduction benefit

- PCSK9 inhibitors

- ezetimibe

(Ezetimibe < Vascepa < PCS9 inhibitors)

For Group 3- Primary Prevention with DM all patients aged 40 - 75 years should receive _______ regardless of calculated ASCVD risk. If LDL ________, change to _________

- moderate-intensity statin

- remains > 100, or < 30% reduction

- high intensity statin

For Group 3- In those with a 10-year risk > 7.5%, presence of _________, increase to high intensity statin. If LDL______ , can consider add-on ezetimibe

- diabetes-specific risk enhancers, or subclinical atherosclerosis

- remains > 70, or < 50% reduction

Diabetes-Specific Risk Enhancers That Are Independent of Other Risk Factors in Diabetes Mellitus

1. Long duration (≥10 years for type 2 diabetes mellitus or ≥20 years for type 1 diabetes mellitus)

2. Albuminuria ≥30 mcg of albumin/mg creatinine

3. eGFR

Calculation required as it determines if treatment will be started or not

Group 4 - Primary Prevention without DM

Group 4 - Primary Prevention without DM the assessment of _______ becomes essential for those at Borderline and Intermediate Risk

Risk Enhancers

Group 4- ASCVD Risk of 5-7.5% (+ Risk Enhancers) OR 7.5-20%

- Moderate intensity

- target > 30% LDL reduction and LDL < 100

- increase to high intensity if needed

Group 4- ASCVD Risk of 20%

- High intensity

- target > 50% LDL reduction and LDL < 70

- add-on ezetimibe if needed

Risk-Enhancing Factors include

1. Family history of premature ASCVD(men aged

Which are the beneficial mechanisms of STATINS that contribute to overall efficacy that are independent of LDL-lowering?

• Anti-inflammatory

• Improvement in endothelial function

• Stabilize atherosclerotic plaques

• Decrease atherosclerotic plaque size

• Reduce thrombogenic response and VTE

Which is likely key feature responsible for disproportionate efficacy of statins relative to other treatments?

pleiotropic effects

The _______ of STATINS also contribute to overall efficacy of statins and are dose dependent effect

pleiotropic effects

In primary prevention, patients who can tolerate an appropriately dosed statin gain no benefit with add-on therapy of:

- Niacin

- BAS

- Fibrates

Which drugs are the CORNERSTONE of antihyperlipidemic therapy?

Statins

Add-on _____ or _____ in high-risk patients and for secondary prevention have proven outcomes.

fish oils (4 g EPA) or PCSK9

____ often recommended but less evidence supporting reduction in outcomes for Group 1 patients

Ezetimibe

_______ beneficial and tolerable for secondary prevention. Similar benefit to low-end high intensity statin*.

Ezetimibe + moderate intensity statin

(Unclear how compares to high intensity statin + PCSK9 / EPA only fish oil, or high-end high intensity statin)

What are the alternatives for those who CANNOT tolerate a statin?

- Bempedoic proven to reduce clinical outcomes in high-risk patients (CLEAR study)

- No head-to-head comparisons of alternative agents

High-intensity statins lower LDL-C by ≥ ________%, Moderate-intensity statins lower LDL-C by %-%, and Low-intensity statins lower LDL-C by < ________%.→ (30%)

≥ 50%

30-49%

< 30%

The two primary high-intensity statins are

Rosuvastatin 20-40 mg and Atorvastatin 40-80 mg

Moderate-Intensity Statins (LDL-C reduction: 30-49%)

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 twice daily (BID)

Pitavastatin 1-4 mg

Low-Intensity Statins (LDL-C reduction:

Simvastatin 10 mg

Pravastatin 10-20 mg

Lovastatin 20 mg

Fluvastatin 20-40 mg

Pitavastatin 1 mg

The approximate equivalent doses of statins are:

1. Rosuvastatin ________ mg

2. Atorvastatin ________ mg

3. Simvastatin ________ mg

4. Pravastatin/Lovastatin ________ mg

5. Fluvastatin ________ mg.

5 mg = 10 mg = 20 mg = 40 mg = 80 mg

Pitavastatin ___ = pravastatin 20 mg

Pitavastatin ___ = simvastatin 20 mg

Pitavastatin ____ = atorvastatin 20 mg

1 mg (1:20)

2 mg (1:10)

4 mg (1:5)

Group 1: For very-high-risk patients on a high-intensity statin, add-on therapy with PCSK9 inhibitor and/or ezetimibe if LDL remains _____________

> 70 mg/dL or < 50 % reduction in LDL

Group 1: For not-high-risk patients on high-intensity statin, add-on with ezetimibe (1st) or PCSK9 (2nd) if LDL remains ________________

> 100 mg/dL or < 50 % reduction in LDL

Group 2: On high-intensity statin, consider add-on with ezetimibe and/or PCSK9 if LDL ___________

doesn't decrease by 50 % or LDL remains > 100 mg/dL.

Group 3: Use at least moderate-intensity statin when ASCVD risk _______ or REs present; if risk _____, use high-intensity.

≥ 7.5 %; > 20 %

Group 3: In high-intensity therapy, add-on _____ if _________

ezetimibe if < 50 % LDL reduction or > 70 mg/dL

Group 4: Begin moderate-intensity statin for risk 7.5-20 %; target ______

30-49 % reduction and < 100 mg/dL

Group 4: If risk _______, escalate to high-intensity statin to target ____________

> 20 %; > 50 % reduction and < 70 mg/dL

Group 4: Add-on with ezetimibe if needed to reach LDL ___________

< 70 mg/dL or < 55 mg/dL for very-high-risk individuals.

Very-high-risk ASCVD goal: LDL ______ and ________ from baseline.

< 55 mg/dL and ≥ 50 % reduction

High-risk ASCVD goal: LDL _____ and _________ from baseline.

< 70 mg/dL and ≥ 50 % reduction

Moderate-risk goal: LDL _______ and _________ from baseline.

< 100 mg/dL and 30-49 % reduction

Add-on order for insufficient LDL lowering:

Ezetimibe → PCSK9 inhibitor

PCSK9 inhibitors are typically considered after __________ when LDL remains above goal.

maximally tolerated statin ± ezetimibe

If ________, reassess adherence, secondary causes, and consider combination therapy.

< 50 % LDL reduction

Routine Monitoring involves checking lab value(s) routinely and repeatedly in the absence of a ______.

clinical problem

________ is checking on a routine basis "just to make sure" everything is still OK when there is nothing going on to prompt you to order the test.

Routine monitoring

Routine Monitoring is generally

not helpful, costly, and burdensome in this setting.

Purposeful Monitoring involves checking lab value(s) to investigate a ______ or when a result is necessary to make a ______.

specific problem; specific decision

Purposeful Monitoring is helpful and important for ______ / ______ in this setting.

safety / efficacy

Routine monitoring of ______ is not necessary for therapy.

statins

AST/ALT monitoring has not been shown to reduce the incidence of ______.

liver toxicity

AST/ALT should be checked at ______ and _______

baseline and when indicated after.

CK monitoring is only recommended when ______ or ___________

clinically indicated or at baseline in those at high risk of muscle-related AEs

Lipid panel should be assessed at baseline and again in ______ weeks after initiation and dose adjustments.

4-12 weeks

Follow-up lipid monitoring is used to evaluate ______ and ____

LDL targets and percent LDL reduction.

Possible add-on therapies for inadequate LDL lowering include ______, ______, and ______.

ezetimibe; PCSK9 inhibitors; EPA-only fish oil

Long-term, repeated testing is not necessary if there is no plan to ____ or _____

adjust dose or add-on therapy

______ have a lower CHANCE of causing side effects, but this does NOT Guarantee that they will not cause side effects.

Hydrophilic statins

Hydrophilic statins include _______ & _______, while Hydrophobic (Lipophilic) include _______ & ________

H2O: Pravastatin & Rosuvastatin

Lipid: Atorvastatin & Simvastatin

Which drugs were used in the STELLAR trial?

Atorvastatin, pravastatin, rosuvastatin, or simvastatin across all doses

For the STELLAR trial AEs were ______________, ______ was reported in 4% of patients overall

- AEs similar across all groups

- Myalgias

True or False: Using lower doses of High intensity statins sacrifices the pleiotropic benefits without guarantee of lower incidence of AE

True