Lipids

When are PCSK9i preferred over ezetimibe

In patients that require >25% additional LDL lowering

If a 3rd nonstatin therapy is warranted, what should be selected

bempedoic acid or replacement of PCSK9i with inclisiran

Who should get high intensity statin therapy

• ASCVD very high risk 

• ASCVD not very high risk and age 75+

• DM age 40-75 with several ASCVD risk factors

• primary prevention age 40-75 with ASCVD risk of 20% or greater

• severe hypercholesterolemia (listed as maximally tolerated statin therapy)

Who should get moderate intensity statin therapy 

• ASCVD not very high risk age >75 

• DM age 40-75 w/out ASCVD risk factors 

• primary prevention age 40-75 ASCVD risk 5-7.4% if risk enhancers are present 

• primary prevention age 40-75 ASCVD risk 7.5-19.9%

When are statins used in patients <40 years old?

• DM age 20-39 - consider statin if several risk factors or risk enhancers 

• severe hypercholesterolemia doesn’t specify ages 

When is ezetimibe added?

• In ASCVD if LDL 70+ w/ statin therapy

• Severe hypercholesterolemia where LDL is reduced by <50% and/or LDL still 100+

• DM if ASCVD risk 20% or more

• If additional LDL lowering is needed for primary prevention

When are PCSK9i added

• very high risk ASCVD if LDL 70+ or non-HDL 100+ on statin and ezetimibe

• severe hypercholesterolemia age 30-75 and LDL 100+

• severe hypercholesterolemia age 40-75 and LDL 130+ with baseline LDL 220+

Primary goal of treated hypertriglyceridemia

prevent pancreatitis

Medications that increase LDL

• amiodarone 

• cyclosporine

• diuretics

• glucocorticoids

dietary influences that increase LDL

• saturated or trans fats

• weight gain

• anorexia

medical conditions that increase LDL

• nephrotic syndrome

• biliary obstruction

• hypothyroidism

• obesity

• pregnancy

Medications that increase TGs

• anabolic steroids

• atypical antipsychotics 

• BB

• bile acid sequestrants 

• glucocorticoids

• hormone therapy

• protease inhibitors 

• raloxifine

• retinoic acid

• sirolimus 

• tamoxifen

• thiazides 

dietary influences that increase TGs

• very low fat diets

• high carb intake

• excess alcohol intake

• weigh gain

medical conditions that increase TGs

• poorly controlled DM

• hypothyroidism

• obesity

• pregnancy

• nephrotic syndrome

• chronic renal failure

• lipodystrophies

moderate hypertriglyceridemia 

TG 175-499 

severe hypertriglyceridemia 

TG 500+

When to start therapy for moderate hypertriglyceridemia 

If TG persistently elevated and ASCVD risk is 7.5% or greater - consider initiation or intensification of statin therapy

*always assess lifestyle, comorbidities and meds

When to start therapies for severe hypertriglyceridemia 

If persistently elevated and ASCVD risk is 7.5% or greater - consider initiation or intensification of statin therapy 

*reasonable to implement very low fat diet and initiate fibrate or O3FA, especially if fasting TG 1000+ 

TG reduction with statins

7-30%

TG reduction with fibrates

20-50%

TG reduction with ezetimibe

5-11%

TG reduction with O3FA

19-44%

What does the pooled cohort equation estimate

risk of fatal and nonfatal MI and stroke

What are the risk enhancing factors

• Family hx of premature ASCVD (<55 men, <65 women)

• Primary hypercholesterolemia (LDL 160-189 or non-HDL 190-219)

• Metabolic syndrome 

• CKD

• Chronic inflammatory conditions (RA, HIV, psoriasis)

• Hx of premature menopause (<40) 

• H/o preeclampsia 

• South Asian ancestry 

• TG 175+

• Elevated CRP, Lpa, ApoB

• ABI <0.9

CAC score of 0

consider no statin

CAC score 1-99

favors statin if age 55+

CAC score 100+ OR 75th percentile 

favors statin 

Statin impact on HDL

increase by 5-15%

Statin impact on LDL

Reduce by 24-60%

Benefits of statin therapy

• reduce major coronary events 

• reduce CV mortality 

• reduce coronary procedures 

• reduce stroke 

• reduce total mortality 

CI for statins

• breastfeeding

• active liver disease, unexplained persistent elevations in hepatic transaminases

• teratogenic

statin DDIs

• fibrates (myopathy, rhabdo - higher risk with gemfibrozil) 

• niacin (doses >1g/day increase myopathy/rhabdo)

Max lovastatin dose with amiodarone

40 mg/day

max simvastatin dose with amiodarone

20 mg/day

max lovastatin dose with dronedarone 

20 mg/day

max simvastatin dose with dronedarone

10 mg/day

max simvastatin dose with amlodipine

20 mg/day

max fluvastatin dose w/ fluconazole

20 mg BID

max atorvastatin dose with itraconazole

20 mg/day

max pravastatin dose with bempedoic acid

40 mg/day

max simvastatin dose with bempedoic acid

20 mg/day

which statins cannot be used with cobicistat

• lovastatin

• simvastatin 

use all statins with caution with this medication

colchicine

which statins shouldn’t be used with cyclosporine

• lovastatin

• simvastatin

• pitavastatin

• atorvastatin

max rosuvastatin dose with cyclosporine

5 mg/day

max pravastatin dose with cyclosporine

20 mg/day

max fluvastatin dose with cyclosporine

20 mg BID

max simvastatin doses with nonDBP CCBs

10 mg/day

max lovastatin dose with nonDHP CCBs

20 mg/day

max atorvastatin dose with clarithromycin

20 mg/day

which statin can be used with gemfibrozil

rosuvastatin at max of 10mg/day

hydrophilic statins

• rosuvastatin 

• pravastatin 

ezetimibe LDL reduction

18-20%

ezetimibe HDL impact

raise 1-5%

which PCSK9i is indicated for homozygous FH

evolocumab 

evolocumab dosing for hetero FH

140 mg SQ q 2 weeks or 420 mg once monthly

evolocumab dosing in homozygous FH

420 mg monthly

Alirocumab dosing

75 mg q 2 weeks or 300 mg monthly

*if LDL lowering inadequate, increase to 150 mg q 2 weeks

inclisiran LDL reduction 

51%

inclisiran dosing

284 mg SQ at months 0, 3, then q 6 months

LDL lowering efficacy of bile acid sequestrants

15-27%

Bile acid sequestrant impact on HDL

increase by 3-5%

bile acid sequestrant mechanism

disrupts enterohepatic recirculation of bile acids so liver is stimulated to convert cholesterol to bile acids

administration of bile acid sequestrants

take other meds 1-2 hours before or 4 hours after bile acid sequestrants

CI to bile acid sequestrants

• TG >400 

• complete biliary obstruction 

fibrate impact on LDL

decrease by 5-20%

*may raise LDL if TG very high

fibrate impact on HDL

raise by 10-20%

fibrate mechanism

reduces rate of lipogenesis in the liver

monitoring for fibrates

monitor LFTs q 3 months x1 year then annually

CI for fibrates

• severe renal or hepatic disease

• pre-existing gallbladder disease

when are fibrates indicated

TG 500+

especially when TG 1000+

TG lowering efficacy of O3FA

26-45%

O3FA impact on HDL

raise by 5-14%

O3FA impact on LDL

can raise if TG high

outcome of REDUCE-IT trial

icosapent ethyl reduced composite CV death, nonfatal MI, nonfatal stroke, coronary revascularization, or unstable angina

O3FA mechanism

• reduced hepatic production of VLDL

• possible reduction in hepatic synthesis of TG

• increased hepatic beta oxidation

bempedoic acid mechanism

inhibits ATP citrate lyase which inhibits cholesterol synthesis in the liver 

ADR/monitoring for bempedoic acid

• gout

• hyperuricemia

• leukopenia

• thrombocytopenia

• tendon rupture

when is bempedoic acid indicated

adjunct to statin therapy in hetero FH OR known CVD in pts who require additional LDL reduction

outcome of CLEAR outcomes trial

bempedoic acid was associated with reduce rates of MACE compared to PBO among primary prevention patients with statin intolerance