Pharmacotherapy of Hyperlipidemics Flashcards
1
Q
AHA-ACC Cholesterol Guidelines
A
- Based on whether management is for primary or secondary prevention
- Primary prevention gets ASCVD risk assessment to determine NEED for statin treatment
- Secondary prevention gets assessed to determine if they are very high risk and what the GOAL of statin therapy/additional therapy (if needed) is
2
Q
ASCVD Risk Assessment - >20 yo w/o ASCVD
A
- Assess traditional ASCVS risk factors every 4-6 years
* *Consider assessing 30-year or lifetime ASCVD risk based on ASCVD risk factors for adults 20-39 y.o.
3
Q
ASCVD Risk Assessment - 40-75 y.o. w/o ASCVD
A
- Assess traditional ASCVS risk factors every 4-6 years
- Assess 10-year ASCVD risk every 4-6 years
4
Q
ASCVS Risk Assessment
A
- Obtain lipoprotein profile (total chol., LDL, HDL, triglycerides)
- Race/ethnicity
- Weight, height
- Physical activity level
- Diet (food/alcohol)
Traditional Risk Factors
- Smoking status (within the last 7 days)
- Hypertension (>130/80)
- Low HDL-C (<40 mg/dl)
- Age and gender (>45 y.o. for men, >55 y.o. for women)
- Diabetes (hemoglobin A1c)
5
Q
Risk-Enhancing Factors
A
- Family history, 1st degree relative, of premature ASCVD (<55 y.o. for men, <65 for women)
- Primary hypercholesterolemia (LDL 160-189, non-HDL-C 190-219)
- Chronic kidney disease (eGFR 15-59)
- Chronic inflammatory conditions (psoriasis, HIV, rheumatoid arthritis)
- History of premature menopause and pregnancy-associated conditions that increase ASCVD (gestational DM and preeclampsia)
- High-risk race/ethnicity (South Asian)
- Metabolic Syndrome
6
Q
Metabolic Syndrome Risk Factors
A
Requires 3 of the following 5:
- Fasting glucose>100mg/dL
- HDL-C <40 mg/dL in males or <50 mg/dL in females
- TGs >= 150 mg/dL
- Waist circumference >40 inches in males or >34 inches in females
- SBP >= 130 mmHg or DBP >= 85 mmHg
- Receiving anti-hypertensive medicatiosn
7
Q
Lipid Biomarkers
A
- Persistently elevated TGs (>= 175 mg/dL)
- Elevatedhs-CRP >=2 mg/L
- Elevated Lp(a) >= 50 mg/dL
- Elevated apoB >= 130 mg/dL
8
Q
ABI
A
- Ankle-brachial Index
- ABI < 0.9 is a risk factor
- Ratio fo SBP measured at the ankle compared to it measured at brachial artery
- Typically used as indicator of peripheral arterial disease (PAD)
9
Q
Measuring LDL/Non-HDL Recommendations
A
- 20 y.o.+ and not on lipid-lowering therapy should have either fasting/non-fasting plasma lipid profile taken to estimate ASCVD risk, also document baseline LDL
- 20 y.o.+ who are found to have a TG >= 400 mg/dL, a repeat lipid profile in a fasting state should be done to assess fasting TG and LDL levels
- Assess fasting plasma lipid profile if they have a family history of premature ASCVD or genetic hyperlipidemia
10
Q
Healthy Lifestyle
A
- Guidelines endorse a healthy lifestyle for everyone
- Reduces ASCVD risk at all ages, can reduce development of risk factors and is the foundation of ASCVD risk reduction
- Lifestyle therapy is the primary intervention for metabolic syndrome
11
Q
Lifestyle Management
A
- Healthier dietary patterns
- Increasing healthy foods (veggies, fruits, whole grains, low-fat dairy, etc)
- Limit sweets, sugar-sweetened beverages, red meats
- Utilize plans such as DASH, USDA food pattern or AHA diet
- Reduce sodium intake (<2400 mg/day)
- Increased physical activity: 150 mins per week of moderate-intense exercise or 75 mins per week of vigorous-intensity exercise
- Healthy weight
- Stop smoking
12
Q
Secondary Prevention: ASCVD not high risk, Age =< 75 y.o.
A
- High intensity statin, goal of lowering LDL by at least 50%
- If high intensity statin isn’t tolerated, use moderate intensity statin
- If on maximal statin therapy and LDL is still >= 70 mg/dL, adding Zetia may be reasonable
13
Q
Secondary Prevention: ASCVD not high risk, Age >75 y.o.
A
- Initiate moderate or high level intensity statin
- Continue high-intensity statin
14
Q
Secondary Prevention: high risk for ASCVD
A
- High intensity or maximal statin
- If on maximal statin an LDL is still above 70 mg/dL, adding Zetia may be reasonable
- If a PCSK9-I is considered, add Zetia to max statin first
- If on maximal LDL lowering therapy and LDL level is still too high ornon-HDL is >100 mg/dL, adding a PCSK9-I may be reasonable
15
Q
Very-High Risk of Future ASCVD Events
A
Previous Events
- Recent acute coronary syndrome within the past 12 months
- History of MI
- History of ischemic stroke
- Symptomatic peripheral arterial disease
Risky Conditions
- > 65y.o.
- Heterozygous familial hypercholesterolemia
- History of coronary artery bypass surgery or percutaneous coronary intervention
- Diabetes mellitus
- Hypertension
- Chronic kidney disease
- Currently smoking
- Persistently high LDL levels despite max statin therapy and Zetia
- History of congestive heart failure
**Need either 2 events or 1 event and 2+ conditions to be considered very high risk)
16
Q
High Intensity Statin Therapy
A
- Goal: daily dose to lower LDL by >50%
- Atorvastatin 80 mg
- Rosuvastatin 20 (40) mg
() - titration option
17
Q
Moderate-Intensity Statin Therapy
A
- Goal: lower LDL by 30-50%
- 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
18
Q
Low-Intensity Statin Therapy
A
- **Simvastatin 10 mg
- Pravastatin 10-20mg
- Lovastatin 20 mg
- **Fluvastatin 20-40 mg
- **Pitavastatin 1 mg
19
Q
ASCVS not at Very High Risk
A
- Encourage healthy lifestyle
- High-intensity statin therapy or maximally tolerated therapy (goal to lower >50%)
- If high-intensity can’t be tolerated attempt moderate-intensity
- If on maximally tolerated statin therapy and LDL is still too high, add Zetia
- If patient is >75 y.o., initiate moderate or high intensity (continue high intensity if already on and tolerating)
20
Q
ASCVS at Very High Risk
A
- Encourage healthy lifestyle
- High-intensity statin therapy or maximally tolerated (goal to lower >50%)
- Add Zetia if necessary
- Zetia should be added BEFORE PCSK9-I
- If on maximal LDL lowering (Statin and Zetia) and LDL or non-HDL are still to high, adding a PCSK9-I is reasonable
21
Q
Primary Prevention: Patients with LDL > 190 mg/dL
A
- Patients 20-75 years of age with severe primary hypercholesterolemia - high intensity statin therapy or maximally tolerated statin therapy
- If <50% reduction of LDL or LDL remains higher than 100 mg/dL, add Zetia
- If <50% reduction of LDL occurs while on a statin + Zetia, BAS may be considered
- If LDL levels still remains high on statin + Zetia and the patient has multiple factors that increase subsequent risk of ASCVD events, a PCSK9 inhibitor may be considering (long term safety is uncertain)
22
Q
Primary Prevention: Patients with Diabetes
A
- 40-75 y.o. with DM and high LDLs, start moderate-high statin therapy
- High risk ASCVD DM patients. especially those with multiple RFs or 50-75 y.o., use high-intensity statin therapies
- IF 10-year ASCVD risk >=20% and has <50% decrease in LDL on maximal statin, add Zetia
- If older than 75 y.o., start statin therapy after a discussion or continue therapy if already on it
- 20-39 y.o. with DM risk enhancers, initiate moderate intensity statin
23
Q
Diabetes-Specific Risk Enhancers
A
- Long duration (over 10 years for type 2, over 20 years for type 1)
- Albuminuria >= 30mcg of albumin/mg creatinine
- eGFR < 60 mL/min/1.73 m^2
- Retinopathy
- Neuropathy
- ABI< 0.9
24
Q
Primary Prevention: 40-75 y.o., no DM, LDL 70-189 mg/dL (Based on ASCVD Risk Assessment)
A
- Risk <5% (Low Risk) - Emphasize lifestyle changes to reduce risk factors
- Risk 5-7.5% (Borderline Risk) - If risk enhancers present, discuss moderate intensity statin, CAC may help with decision process
- 7.5-20% (Intermediate Risk) - if risk estimate and enhancers favor statins then prescribe moderate intensity statin (if uncertain, consider measuring CAC)
- > 20% (High Risk) - initiate statin to reduce LDL >= 50%
25
Q
CAC Scores
A
- Coronary Artery Calcium Score
- If zero, withhold statin therapy and reassess in 5-10 years as long as higher risk conditions are absent
- If 1-99, start statin therapy for >=55 y.o.
- If >100 or >= 75th percentile, initiate statin therapy
26
Q
CAC
A
- Computed tomography of chest
- Measures amount of calcified plaque in coronary arteries
- Zero - low risk
- 1-99 - mild plaque development
- > 100 - moderate amount of plaque
27
Q
Monitoring
A
- Assess adherence and percentage response to LDL lowering medications and lifestyle changes with repeat lipid measurement 4-12 weeks after statin initiation or dose adjustment
- Repeat every 3-12 months as needed
- Define responses to lifestyle and statin therapy by percentage reductions in LDL levels compared with baseline
28
Q
Primary Prevention: 20-39 y.o.
A
- 10-year ASCVD risk not available using PCE
- Can use to estimate Lifetime risk
- Consider statin therapy if family history of premature ASCVD and LDL >= 160 mg/dL
29
Q
Primary Prevention: >= 75 y.o.
A
- If LDL levels between 70-189 mg/dL, initiating a moderate-intensity statin may be reasonable
- May be able to stop statin therapy when functional decline, multimorbidity, frality, or reduced life-expectancy limits the potential benefits of statin therapy
- In 76-70 y.o. with LDL 70-189 mg/dL, may be reasonable to measure CAC to reclassify those with a CAC score of zero to avoid statin therapy
30
Q
Primary Prevention: Pediatrics
A
- Children/adolescents with lipid disorders related to obesity, recommend to intensify lifestyle therapy
- In children >10 y.o. with persistent LDL >190 or >160 with possible FH, not responding to 3-6 mo. of lifestyle therapy, reasonable to start statin therapy
- IF family history of premature CVD or primary dyslipidemia, reasonable to measure fasting lipid profile as early as 2 y.o. to detect FH or primary dyslipidemias
- In children w/o CV risk factors of family history of ASCVD, may be reasonable to measure lipid rpofile between 9-11 y.o. and again at 17-21 y.o.
31
Q
Recommendations for Hypertriglyceridemia, > 20 y.o.
A
-Those with moderate hypertriglyceridemia should have lifestyle factors addressed, secondary factors assessed, and consider medications that increase TGs
32
Q
Recommendations for Mod-Sev Hypertriglyceridemia, 40-75 y.o.
A
- ASCVD risk >= 7.5%, reevaluate ASCVD risk after lifestyle and secondary factors are addressed
- Consider persistently high TG levels as a factor favoring the initiation or intensification of statin therapy
33
Q
Recommendations for Severe Hypertriglyceridemia, 40-75 y.o.
A
-ASCVD >= 7.5%, reasonable to address reversible causes of high TGs and initiate statin therapy
34
Q
Recommendations for Severe Hypertriglyceridemia (esp fasting TGs >= 1000 mg/dL)
A
- Reasonable to identify and address other causes for raised TGs
- Persistently elevated/increasing TGs, reduce TGs with low-fat diet, avoid refined carbs and alcohol, consume omega-3 fatty acids
- If needed to prevent acute pancreatitis, utilize fibrate therapy
35
Q
Statins
A
- MOA: inhibit HMG-CoA Reductase, increases hepatic LDL receptors
- Decreases LDL, decreases TGs, increases HDL
36
Q
Statins reduce…
A
- Major coronary events and stroke
- CV-related and total mortality
- Coronary procedures (PCI/CABG)
- In general, for every 1% reduction in LDL and 1% reduction of ASCVD event is achieved
37
Q
Cholesterol Treatment Trialists’ Collaborators
A
- Meta-analysis of 27 statin studies
- 175,000 patients with and without vascular disease
- Relative risk per 1 mmol/L LDL reduction based on baseline 5-year CV risk
38
Q
Statin Drug Interactions
A
- Simvastatin and Lovastatin - CYP3A4 inhibitors (grapefruit juice)
- Atorvastatin - less first pass metabolism so small increases in concentration
- Fluvastatin - CYP2C9 metabolism, few interactions
- Pravastatin and rosuvastatin - not metabolized by CYP
- Most statins are affected by OATP1B1 inhibitors like gemfibrozil and cyclosporine
39
Q
Safety Summary for Statins
A
- Excellent patient acceptance
- Relatively low cost
- Few SEs: GI most common, high intensity can elevate liver enzymes
- Myopathy and rhabdomyolysis are also rare possibilities
- Increases risk of DM
- Allergies are rare
- No increases in total or non-CHD mortality
40
Q
Myopathy
A
General term referring to any disease of muscles; can be acquired or inherited and can occur at birth or later in life
41
Q
Myalgia
A
Muscle ache or weakness without creatine kinase elevation
42
Q
Myositis
A
Muscle symptoms with increased CK levels
43
Q
Rhabdomyolysis
A
Muscle symptoms with marked CK elevation (>10x the upper limit), usually accompanied with brown urine.
44
Q
Safety Reccs BEFORE starting Statins
A
- Counsel patient on healthy lifestyle
- Obtain baseline ALT
- Obtain baseline CK and indicateifthere is a family history/past history of myopathy
- Determine baseline muscle pain or weakness
- Obtain HgbA1c, if not already collected
- Determine baseline confusion/memory state
45
Q
Safety Reccs while taking Statins - Myopathy
A
- Monitor for myopathy with each visit
- If myopathy is severe (intolerable), D/C statin and check CK, creatinine, and a urinalysis
- Mild-moderate symptoms: D/C statin and check CK, if CK <10x ULM lower the strength of the same statin then D/C if symptoms recur
- IF after 2 months of no statins, symptoms or elevated CK do not improve, consider other muscle problem and restart statin
46
Q
Safety Reccs while taking Statins - Liver Toxicity + Others
A
- Monitor for liver toxicity (weakness, loss of appetite, abdominal pain): if present, measure hepatic function
- Evaluate for new-onset DM
- IF experiencing confusion/memory worsening, evaluate for nonstatin causes
- CI: pregnancy, lactation
47
Q
Statin Counseling
A
- Take at the same time everyday (Lova, sim, and fluva to take a bedtime)
- Report unexplained muscle pain, tenderness, or weakness
- Report symptoms of liver dysfunction
- Check lipid profile 4-12 weeks following starting statin, then periodically
- May cause stomach upset or headache, usually goes away from 1-2 weeks
- Drug interactions
48
Q
BABs
A
- MOA: block reabsorption of bile acids in the intestine which causes the liver to convert more cholesterol into bile (increases LDL receptors)
- 15-30% reduction in LDL; increase HDL 3-10%, INCREASES TGs 0-12%
- Reduce major coronary events and CHD deaths
- Adverse effects: GI (bloating and constipation), increases TGs
- Absolute CI: biliary obstruction, fasting TGs > 300 mg/dL (possibly if ranging from 250-299 as well)
49
Q
BAB Drug Interactions
A
-Decreases absorption of anionic drugs (cyclosporine, phenytoin, glimeperide, warfarin, fat-soluble vitamins, etc.)
50
Q
BAB Dosing/Monitoring
A
- Cholestyramine: 4-24 gm/d
- Colestipol: 5-30 gm/d
- Colesevelam: 3.8-4.2 gm/d
Monitoring: Fasting lipid profile 3 months after starting and then every 6-12 months. CBC yearly.
51
Q
BAB Counseling
A
- Start low and titrate dose up gradually
- Split doses (BID)
- Drink plenty of fluids
- If a powder, mix with at least 6oz of juice or water, mix slowly to avoid foaming, and refrigerate to help the taste
- Take before or with meals
- Mix with psyllium to help with constipation
52
Q
Zetia
A
- Selective cholesterol absorption inhibitor
- Binds to NPC1L1
- Dose: 10 mg QD
- Available in combination with simvastatin
- Decreases LDL 15-20%, increases HDL 4-9% as monotherapy and a add-on
- No data on CV morbidity or mortality
- No effect on blood levels of fat soluble vitamins
53
Q
Zetia Monitoring
A
- Lipid profile 4-12 weeks after starting
- May increase risk of liver enzyme elevation when used with statins, so obtain baseline of these levels and repeat if symptoms arise
54
Q
IMPROVE-IT
A
- Vytorin (Zetia+Zocor) v.s. Zocor in 18,144 patients with ACD for a median of 7 years
- Lowered LDL more as a combo than zocor alone
- Reduced CV-related death by 6.4%
- 2.0% risk reduction overall compared to the Zocor alone
55
Q
Evolocumab (Repatha)
A
- PCSK9-I
- Approved in 2015 to be used with a diet
- Reduces risk of CV events
- Recommended for those on maximally tolerated statin therapy or other LDL lowering therapies who need additional LDL lowering
- Dosing: 140 mg SC q2w, OR 420mg SC monthly
- EXPENSIVE
56
Q
Fourier Study
A
- 27,564 patients with ASCVD and on high-intensity statins
- Added Evolocumab at one of the specified dosing and placebos
- LDL decreased by 59%
- CV-related deaths decreased by 15%
57
Q
Alirocumab (Praluent)
A
- PCSK9-I
- Approved in 2015 to be used with a diet and maximally tolerated statin therapy with inherited hypercholesterolemias
- Dose: 75 mg SC q2w, can increase dose to 150 mg if response if insufficient
- EXPENSIVE
- Store in fridge, let warm to room temp for 30-40 minutes before injection
58
Q
Odyssey Outcomes Trial
A
- 18,924 patients with recent ACS on max tolerated atorvastatin or rosuvastatin with high LDL or non-HDL
- CV-related deaths decreased by 15%
59
Q
PCSK9-I Comparison
A
- Similar efficacy in terms of LDL reduction (45-70%)
- Monotherapy or add-on
- SE have been minimal
- Nasopharyngitis, injection site reactions, and influenza
60
Q
Omega-3 Fatty Acids (Fish Oil)
A
- Effective at lowering TGs (25-30%), increase LDL (5-10%), especially at high doses
- Minimal effects on HDL
- MOA: not understood, possibly increases plasma LPL and decreases hepatic lipogenesis
- Showed to decrease CHD events
61
Q
Omega-3 Fatty Acids (Drug Examples)
A
- Lovaza - 960gm per capsule: indicated for TGs > 500 mg/dL, 4 grams daily
- Vescepa - 1gm per capsule: indicated TGs > 500 mg/dL, dose 2 gm BID
- Epanova - approved for TGs > 500 mg/dL, dose 2 gm or 4 gm daily
- Max EPA: 1 gm/capsule, titrate to max of 4gm/day (12 capsules)
62
Q
Omega-3 SE
A
- At higher doses can effect bleeding time
- May impair insulin secretion
- GI: nausea, diarrhea, eructation, taste disturbance
63
Q
REDUCE-IT Trial
A
- 8,179 patients with ASCVD or diabetes and additional CV RFs on statins with elevated TGs and LDL
- Primary EP: composite of CV death, nonfatal MI, nonfatal stroke, coronary revascularization, or unstable angina
- Median follow-up: 4.9 years
- Results: Primary EP occured 17.2% of Vescepa patients (5% less than placebo), CV death also decreased
64
Q
Fibric Acid Derivatives
A
- Activation of PPAR(alpha), lipolysis and increases LPL activity which decreases serum VLDL and upregulates ApoA1 which increases HDL
- Decreases TGs 30-50%, increases HDL by 10-20%, may slightly increase OR decrease LDL
- Reduces major coronary CV events by 10% with no effect on CV mortality
- Adverse effects: GI upset, gall stones, hepatotoxicity, myopathy, neutropenia, thromboembolism
65
Q
Fibric Acid Monitoring
A
- LFTs at baseline, 6-12 weeks, then about q3 months
- Serum creatinine and eGFR at baseline, 3 months, and q6m
- CBC at baseline then periodically
- Baseline CK
66
Q
Fibric Acid CI
A
- Hepatic dysfunction
- Severe renal disease
- Gallbladder disease
67
Q
Fibric Acid Drug Interactions
A
- Warfarin (increase PT/INR)
- Statins (increase myopathy)
- Cyclosporine (increases [fibrate])
- *Don’t use gemfibrozil with statins, fenofibrate okay with low-moderate intensity statins**
68
Q
Fibrate Patient Counseling
A
- Report unexplained muscle pain, tenderness, weakness
- Report severe abdominal pain
- Lipid profile (4-6 weeks after starting, then periodically), liver enzymes (LFT baseline, 6-12 weeks after, then q3mo), and kidney function (SCr and eGFR baseline, 3 mo later, then q6mo)
- May cause stomach upset which should stop after 1-2 weeks
- Drug interactions
69
Q
Niacin
A
- MOA: reduces hepatic VLDL synthesis which reduces LDL and TGs
- Decreases LDL 5-25%, TGs 20-50%, increases HDL 15-30% with crystalline (less with SR)
- Reduces major coronary events and possibly mortality
- Adverse Effects: flushing, pruritis, skin rash, abdominal pain, hepatotoxicity, hyperglycemia, hyperuricemia
70
Q
Niacin Monitoring
A
- FBG or Hba1c, uric acid (baseline and q6mo)
- Hepatic enzymes (baseline, monthly during dose stabilization, q3mo for first year on SR or at dose threshold for IR/ER)
- Check LFTs q6mo
71
Q
Niacin CI/DI
A
CI
- Relative: DM, gout, peptic ulcer
- Absolute: liver disease (don’t use if enzymes at 2-3x ULN), new onset atrial fibrillation
-DI: Statins (increased risk of myopathy)
72
Q
Niacin Dosing
A
- Start low and go slow
- IR: 100 mg TID x 1w, 250 TID x1w, 500mg TID x1w then assess. Can increase to 750 mg TID and then 100mg TID if needed
- ER: 500mg qhs x4w, then 1000mg QHS, may increase to 2000 mg if needed
- SR: 250 mg BID then increased weekly to 1.5-2gm
73
Q
Niacin Counseling
A
- Slow titration
- Take with low-fat snack or meal
- Administer aspirin (325mg) 30 minutes prior to first dose of niacin if no CIs
- Take at bedtime (SR or ER)
- Avoid other vasodilatory activities (alcohol, hot beverages, spicy foods, hot showers/baths, vigorous physical activity)
74
Q
Red Yeast Rice
A
- Activity against HMG-CoA Reductase
- Lowers LDL 20-25%
- Counsel on the need for monitoring
- Linked to myopathy, hepatotoxicity, and rhabdomyolysis
75
Q
Chinese Coronary Secondary Prevention Study
A
- Showed Red Yeast Rice significantly reduced CV events, CV mortality, and total mortality
- Studied 4,870 patients for 4.5 years
- Capsules used contained a combination of lovostatin, ergosterol, and other components
76
Q
Psyllium Husk
A
- Metamucil
- Good, lowers LDL 10-15%
77
Q
Garlic
A
- Probably good
- Lowers LDL 2-3 mg/dL
78
Q
Olestra
A
- “WOW”
- Not so good
- TC lowered 5-8%
79
Q
Policosanol
A
-Not good in controlled clinical trials
80
Q
Guggalipid
A
-Controlled trials weren’t impressive
81
Q
Cinnamon
A
- Goof
- Lowered LDL 9 mg/dL
82
Q
Green Tea Extract
A
- Good
- Lowered LDL 5 mg/dL
83
Q
Almonds
A
- Good
- Lowered LDL 6 mg/dL
84
Q
Plant Stanols/Sterols
A
- Good
- Lowered LDL 12 mg/dL
