Hyperlipidemia Flashcards
(139 cards)
1
Q
How long should one undergo lipid therapy?
A
Indefinitely
2
Q
Lipid levels return to pretreatment levels in how much time?
A
2-3 weeks
3
Q
Lipid-lowering drugs in conjunction with ________ and _______ optimize prevention of heart disease
A
Diet changes & exercise
4
Q
Drugs that lower LDL can prevent progression, slow progression, & cause regression of…..
A
Atherosclerotic disease
5
Q
Most cholesterol in carried in
A
LDL (unless increased TGs)
6
Q
____ TG levels and _____ HDL levels increase risk for heart disease
A
Increased; decreased*
*even if LDL is normal
7
Q
If you decrease TGs, you will likely
A
Increase HDL
8
Q
Shape of saturated FAs
A
Straight chained
9
Q
Saturated FAs vary in
A
Chain length
10
Q
Unsaturated FAs vary in
A
Number, position, & geometry of double bonds
11
Q
Double bonds of naturally occurring oils & fats are in the ____ configuration
A
Cis
12
Q
Double bonds of industrial products are in the ____ configuration. What are the implications of this?
A
Trans
Raises the melting point
13
Q
2 components of prevention
A
Exercise & diet
14
Q
What diet has the best data
A
Mediterranean
15
Q
Screening recommendations (two steps)
A
Step 1: Assess for traditional RF (e.g. BP, DM, smoking) q4-6yr in pt. 20-79
Step 2: Based on lipid & RFs, calculate 10 yr ASCVD risk
16
Q
Lipoprotein abnormalities are classified into 2 groups:
A
- High LDL
2. Combined dyslipidemia (low HDL, high TG, high non-HDL, normal LDL)
17
Q
Why did the approach to guidelines change? (NCEP/ATPIII - 2004 -> ACC/AHA - 2013)
A
Aiming for LDL targets is NOT based on evidence
18
Q
New ACC/AHA guidelines focus on these 3 things:
A
- Statins
- Less use of non-statins (e.g. fibrates, niacin, bile acid sequestrants etc.)
- Abandon LDL “goals”
19
Q
What does the ACA/AHA CVD risk calculator determine?
A
Patient’s 10-year risk of AMI or CVA
20
Q
How does the ACA/AHA CVD risk calculator determine?
A
Based on patient’s sex, age, race, total and HDL cholesterol, diabetes, systolic BP, HTN tx, & smoking status
21
Q
ACA/AHA CVD risk calculator is used for
A
PRIMARY prevention
22
Q
ACA/AHA CVD risk calculator is not valid if
A
The patient is being treated (use pre-statin values to assess risk)
23
Q
Why does mot ASCVD events occurs in lower risk patients?
A
Because they make up most of the population
24
Q
Who gets a high-intensity statin?
A
- Pt. w/ clinical atherosclerotic CVD
- Pt. w/ DM + age 40-75 + LDL 70-189 AND an ASCVD risk >7.5%
- Pt. w/ LDL >190
25
Who gets a moderate-intensity statin?
- Pt. w/ DM + age 40-75 + LDL 70-189 AND an ASCVD risk <7.5%
- Pt. w/o DM + age 40-75 + LDL 70-189 AND an ASCVD risk >7.5%*
* eligible for moderate-to-high-intensity statin therapy
26
Examples of high intensity statins
Atorvastatin
| Rosuvastatin
27
Examples of moderate intensity statins
```
Atorvastatin (lower dose c/t high)
Rosuvastatin (lower dose c/t high)
Simvastatin
Pravastatin
Lovastatin
Fluvastatin
Pitvastatin
```
28
High intensity statins lower LDL how much
>50%
29
Moderate intensity statins lower LDL how much
30-49%
30
NICE recommends using ________ toool to calculate % risk of developing CVD
QRISK2
31
What does QRISK2 take into accound
Age, smoking hx, cholesterol, BP, Afib, BMI, & FH of HD
32
R/o secondary causes of hyperlipidemia if LDL-C >_____ on initial evaluation
190mg/dL
33
What else must you do if pt. has LDL-C >190mg/dL on initial eval?
Screen family members
34
Causes of secondary hyperlipidemia (must r/o)
- Meds
- Hypothyroidism
- Obstructive biliary disease
- Nephrotic disease
35
Universal lipid screening in pediatric patients occurs in those __-__yr and __-__yr
9-11; 17-21
36
Screen pediatric patients if they
- Use tobacco
| - Have HTN
37
What drug classes target LDL?
- HMG-CoA reductase inhibitors (statins)
- Cholesterol absorption inhibitors
- Bile acid sequestrants
- PCSK9 inhibitors
38
"Newer" statins
```
Atorvastatin
Rosuvastatin
Simvastatin
Pravastatin
Pitvastatin
```
39
"Older" statins
Lovastatin
| Fluvastatin
40
What formulation do all statins come in
Tablets
41
Which statin is the most potent, cheapest, has the best data & fewest CYP interactions
Atorvastatin
42
Which statins do we actually use?
Atorvastatin
Rosuvastatin
Simvastatin
43
Statin MOA
Inhibit de novo synthesis of cholesterol via inhibition of HMG-CoA reductase (decrease synthesis -> increased LDL-R expression -> more LDL cleared from the blood)
44
Lipid effects of statin
↓ LDL
↓TG
Modest ↑ in HDL
45
Other beneficial effects of statins
- Improve endothelial fcn
- Replace plasma viscosity
- Plaque stabilization (↓ plt aggregation & thrombin formation)
- Reduce inflammation
46
Primary indication for statins
Primary AND secondary prevention of CAD
47
Other indications for statins
- DM (@ diagnosis)
| - Post-AMI (upon d/c home)
48
When should simvastatin, lovastatin, fluvastatin be dosed and why?
qhs d/t short 1/2 life
49
When should atorvastatin, rosuvastatin, pravastatin, pitvastatin be dosed and why?
any time d/t long 1/2 life
50
Up to __% of pt. on a statin stop taking in within a year?
50
51
What do we monitor in pt. on statins?
- LFTs
- Fasting BS, HgBA1C
- CPK
- Fasting lipid profile (1-3mo after tx initiated, then q3-12mo -> monitor adherence & lifestyle)
52
What is a risk of scheduling a f/u appt for a fasting lipid panel?
Pt. non-adherence
| Do it same day: nonfasting lipid profile > no lipid profile
53
Most cases (~60%) of statin-induce rhabdo are due to....
Drug interactions
54
Simvastatin and atorvastatin are CYP___ substrates
3A4 (major)
55
If simvastatin and atorvastatin are given with CYP3A4 inhibitors, there is an increased risk of
Myopathy (x5)
56
Some statins are P-gp substrates (sim > ator > prava). If given with P-gp inhibitors such as ______, ______, _____, _______ may increase risk of myopathy
Clarithro, non-DHP CCBs, amiodarone, carvedilol
57
Niacin + statin =
Additive myopathy
58
Fibrates + statin =
Additive hepatotoxicity or myopathy (AVOID!)
59
How do fibrates (esp. gemfibrozil) cause hepatotoxicity
Inhibit hepatic glucuronidation of statin -> interferes statin elimination
60
Simvastatin + dabigatran =
↑ hemorrhage risk
61
Statins + daptomycin =
↑ myopathy risk
62
Which statin is most associated with rhabdomyolysis
Simvastatin
63
How can we further evaluate a patient who complains of myalgia
Vitamin D deficiency, thyroid disorder, polymyalgia rheumatic (PMR)
64
What lab should we get initially and recheck with complaints of myalgia
CPK
65
At what CPK levels should we consider stopping or stop statin?
Consider if <3-10x ULN
| Stop for severe sx or >10x ULN
66
What must we do before blaming the statin for causing myalgia, weakness, or rhabdo in a patient?
r/o other causes (e.g. vitamin D deficiency)
67
Adding exercise to statin therapy improves
Survival (better than either alone)
68
Should we encourage pt. on statins to increase duration or intensity of exercise first?
Duration
69
What should we do if a pt. on a statin has ↑ LFTs (>3x ULN)?
Consider switching to another statin or low the dose of the same one
70
Statins are ok in patients with elevated LFTs d/t
Chronic stable liver disease (esp. NASH)
| - Statin may even ↓ LFTs AND ↓ inflammation
71
Statins proven to ↑ _______ & _______
HbA1C & blood glucose (mostly in pt. with DM RF)
72
What statin is more likely to cause ↑ HbA1C & blood glucose
It's a class effect (& it's dose-dependent)
73
Adding what drug can mitigate the↑ HbA1C & blood glucose caused by statins?
Metformin (the lectures are TALKING)
74
What must your consider prior to choosing a statin
- Degree of hyperlipidemia
- Pk properties
- Presence of renal impairment
- Presence of chronic liver disease
- Cost & data
75
Which statins are good for pt. with renal impairment as they do not require a dose adjustment
Atorvastatin, fluvastatin
76
Which statins are probably safest for pt. with chronic liver disease?
Low dose pravastatin or rosuvastatin
77
What drug is a cholesterol absorption inhibitor?
Ezetimibe
78
Ezetimibe MOA
Inhibit intestinal absorption of both dietary & biliary cholesterol by blocking transport at SI brush border -> ↓ LDL (20-25%)
79
Ezetimibe may ↑ the effect of what drug
Warfarin
80
What should we monitor in pt. on ezetimibe
FLP
81
Bile acid sequestrants
Cholestyramine
Colestipol
Colesevelam
82
Bile acid sequestrant MOA
Enhance excretion of bile salts by binding to them -> liver must use cholesterol to make new salts -> promotes synthesis of LDL receptors -> LDL receptors bind plasma LDL
83
Lipid effects of bile acid sequestrant
↓ LDL (up to 20%)
| May raise TG in pt. with hypertriglyceridemia
84
Do NOT use bile acid sequestrants if TGs >____
300
85
Which bile acid sequestrant is more tolerable?
Colesevelam
86
What should we monitor in pt. on bile acid sequestrants?
FLP
87
Drug interactions of bile acid sequestrants
- No systemic interactions (not absorbed systemically)
| - May bind & impair absorption of other drugs (e.g. digoxin, warfarin, fat soluble vitamins, other anti-lipid meds)
88
How do we mitigate drug interactions w/ bile acid sequestrants?
Give other meds 1 hr before or 4-6 hours after bile acid sequestrants
89
In what patient population should we avoid the use of bile acid sequestrant
Pt. w/ bowel disease
90
ADR of bile acid sequestrants
GI intolerance (constipation)
91
PCSK9 inhibitors
Alirocumab
| Evolocumab
92
PCSK9 inhibitor MOA
Monoclonal Abs target & prevents PCSK9 binding (normal physiology: PCSK9 binds to LDL receptors on hepatocytes -> promotes receptor degradation -> prevents LDL-C clearance from blood & ↑ serum LDL)
93
PCSK9: rate of cholesterol clearance __ rate of synthesis
>
94
Clinical indication for PCSK9
- Adjunct to diet + maximally tolerated statin therapy for adults w/ hetero or homozygous familial hypercholesterolemia
- Approved for pt. w/ ASCVD who require additional LDL lowering
95
Route of PCSK9
Injection
96
Lipid effects of PCSK9
↓ LDL-C ~60% (additional reduction when combined with statin)
97
PCSK9 pearls
$$$
| May need to store in fridge & warm before use
98
What drug classes target HDL & TGs?
- Niacin
99
What B vitamin is niacin?
3
100
Niacin MOA
Inhibits mobilization of FFA from adipose tissue to liver -> ↓ synthesis & secretion of VLDL & ↓ conversion of VLDL to LDL
Can also ↑ HDL (via reduction of lipid transfer of cholesterol from HDL to VLDL & delayed clearance of HDL)
101
Lipid effect of niacin
↑ HDL 15-35%
↓TG 10-50%
↓ LDL 5-25%
102
When do we dose niacin
qhs (start @ 500mg x1mo, then titrate to max dose SLOWLY)
103
Recent studies showed that adding niacin to a statin......
Does NOT improve outcomes more than statin alone
104
Niacin has been found to be associated with
A small increased risk of ischemic CVA (AIM-HIGH trail = death of niacin)
105
What do we have to monitor in pt. on niacin?
- CPK
- FLP
- LFTs (baseline, then q6-12wks, then 6mo)
- Uric acid & glucose (baseline fasting, at 3mo, then annually or as clinically indicated)
* glucose bump is substantial
106
Careful with coadministration of niacin w/ these two drug classes
Statins & fibrates
107
Niacin ADRs
- FLUSHING (mostly IR)
- Hepatotoxicity (mostly sustained release)
- May aggravate glucose & gout (avoid in these pt.)
* ER has the least flushing & hepatotoxicity
108
How are we approaching lowering TGs that is different than in the past?
- No longer relying on fibrates
- More use of fish oil and lifestyle changes (modest wt. loss, ↓ added sugars, eliminating trans fat, ↑ fiber & unsaturated fats, limiting alcohol can ↓ TGs)
109
What drug classes target TGs?
- Fibric acid derivatives
| - Fish oils
110
Examples of fibric acid derivatives
Gemfibrozil
Fenofibrate (micronized, non-micronized)
Fenofibric acid
111
Fibric acid derivatives MOA
PPAR-alpha agonist
112
Lipid effects of fibric acid derivatives
↓ LDL (minimal effect w/ gemfibrozil, ↓20% with fenofibrate
↓TG 25-50%
May ↑ HDL
113
Other clinical uses of fibric acid derivatives
- Persistent hypertriglyceridemia severe enough to be at rik for pancreatitis (>800mg/dL)
- Fenofibrate has uricosuric activity & is used for gout prevention
114
Fibric acid derivatives contraindication in patients with
Liver or gallbladder disease
115
What do we have to monitor in pt. on fibric acid derivatives?
- CPK (if concurrent statins or niacin)
- FLP
- LFTs (baseline, then q6-12wks, then 6mo)
116
Gemfibrozil is a strong inhibitor of CYP___ & CYP___
2C9 & 2C19
117
What might happen if a pt. is taking fibric acid derivatives and a TZD for DM?
They are both PPAR agonists -> may potentiate them (increase effects)
118
We should use fibric acid derivatives with what other lipid-lowering drug class?
Statins (overlapping toxicities)
119
ADRs of fibric acid derivatives
Overall well tolerated
- N/V, dyspepsia M/C
- Reversible hepatotoxicity
- Myositis & rhabdo (mostly gemfibrozil, check CPK w/ muscle complaints)
120
Two types of fish oils
Both are long-chain unsaturated omega-3 fatty acids
- Lovaza* contains EPA & DHA -> DHA may raise LDL in some pt.
- Vascepa* contains only EPA -> less effective at ↓ TGs
* brand names
121
Fish oil MOA
Reduce hepatic TG production & ↑ TG clearance
122
Lipid effects of fish oils
↓ TGs 20-50%
Long-term use may ↑ HDL
*no current evidence that fish oils prevent CVD
123
Fish oil pearls
- OTC products cost LESS than brand name drugs but require 3x daily dose for same effect
- Do NOT interact with statins
- Supplements are mercury-free
- Seafood allergy to fish protein not oil, but advise pt. to be cautious with use
124
What do we monitor with fish oils?
FLP
125
High doses of fish oils have what effect? (potential drug interaction)
Anti-plt effect (caution w/ other drugs that effect coag)
126
ADRs of fish oils
Generally well-tolerated
| - Eructation (burping), dyspepsia, unpleasant aftertaste M/C
127
Approach to lipid management (two steps)
Step 1: decide if therapy is indicated (shared decision-making + risk calculator)
Step 2: start mod to high intensity statin
128
When do we consider a non-statin?
Statin intolerant pt.!
- Non-statins as ADD ON: Add for pt w/ CVD who can't tolerate a high-intensity statin or don't get expected LDL-lowering effect
- Non-statins as MONOTHERAPY: reserve for pt. at high CV risk who cannot take a statin
129
What non-statin do we choose as ADD ON therapy in statin-intolerant pt.?
Ezetimibe
| - Improves CV outcomes when added to statin (use in pt. post-ACS)
130
What non-statin do we choose as MONOTHERAPY therapy in statin-intolerant pt.?
- Bile acid sequestrants -> may improve outcomes when used alone
- Ezetimibe - no evidence that it has CV benefit alone
- PCSK9 inhibitors - for VERY HIGH RISK PT
131
Good therapy regimen for pt. w/ high LDL
Statin +/- ezetimibe pr PCSK9 inhibitors
132
Good therapy regimen for pt. w/ TG >500-1000
Fish oils > fenofibrate
133
Good therapy regimen for pt. w/ low HDL
↓ fructose & increase fiber to ↓ TGs
| Add exercise, wine, & EVOO
134
ABCDE approach to pt. with metabolic syndrome
```
A: assess CV risk & ASA therapy
B: BP control
C: cholesterol/lipid mgmt
D: DM prevention & diet therapy
E: exercise therapy
```
135
What lipid-lowering drugs are category X
Statins
136
What lipid-lowering drugs are category C
- Fibric acid derivatives
- Bile acid sequestrants
- Ezetimibe
- Niacin (can be A depending on dose)
- Omega 3 FAs
137
Take home message for lipid-lowering drugs in pregnancy
Generally do NOT treat lipids in pregnant women
138
What is homozygous familiar hypercholesterolemia (HoFH)?
Rare inherited condition that is commonly caused by defects in the LDL receptor gene
- Causes VERY HIGH LDL levels & premature CVD & death w/o tx
139
Two FDA approved drugs for HoFH
Mipomersen
| Lomitapide
