Dyslipidemia: Therapeutics Flashcards
(99 cards)
1
Q
How to calculate ARR
A
C event rate - intervention rate
—- as this decreases, NNT increases
2
Q
How to calculate RR
A
Intervention/control
3
Q
RRR
A
1-RR
4
Q
Steps to screening for dyslipidemia
A
1) history + physical exam
2) lipid panel: TC, LDL, HDL, TG, A12, FPG
3) eGFR
lipoprotein A — once in a person’s lifetime
5
Q
Treatment approach
A
1) determine if has standard CV RF: HTN, obesity, dyslipidemia, PA, smoking
2) calculate risk using calculator to get risk level
3) talk to pt about risk
4) all should be encouraged for non pharms
6
Q
T or F: all people with clinical CVD should get a statin
A
T
7
Q
When should people with DM get statins
A
> /=40 or > 15yr history of DM + 30yrs old or microvascular complications
8
Q
When should people with CKD get statins
A
> 3 mths duration + ACR > 3 OR eGFR < 60 + 50yrs +
** primary prevention
9
Q
What LDL level should people generally be to get statin
A
> 5 or apoB > 1.45 or non HDL >/=5.8
— or documented FH or genetic reasons
** normal is 3.5
10
Q
What conditions automatically get statins
A
CVD, DM, CKD, or FH, LDL > 5
— if don’t have — look at risk
11
Q
A
12
Q
T or F: if high CV risk, automatically get therapy for dyslipidemia
A
T
13
Q
when deciding whether or not to give someone therapy: what do you do if they are low/medium CV risk ?
A
look at other biomarkers to see if qualify for therapy
14
Q
Which low risk CV pt qualify for therapy
A
LDL >/=3.5 or non HDL > 4.2 or apoB >/=1.05
15
Q
What intermediate risk CV pt get therapy
A
LDL >/=3.5 or non HDL >4.2 9or apoB > 1.05
ORR men >/=50 + w >/=60 w/ one extra RF
16
Q
If someone doesn’t qualify for therapy based on their CV risk, what do you do?
A
recommend non pharms
17
Q
Healthy behaviours are found to be associated with a ______ lower risk of CVD outcomes
A
60-80%
18
Q
What are the main non pharm options for dyslipidemia
A
1) smoking cessation
2) healthy diet : lots of fruits + veggies, low sat fat + high PUFA, refer to dietician, BMI (18.5 -25) and waist < 88 (W) and <102 (M)
3) PA - 150mins/wk
4) decrease stress
5) moderate alcohol intake </= 2 drinks/day (MAX0
—— max of 14 (M) and 9 (F) a week
19
Q
What did the nurse health study show
A
looked at healthy nurses + 14 yr MACE
— recorded lifestyle
Results — increase in good lifestyle choices decrease RRR of MACE (smoking, PA, diet, alcohol, weight)
20
Q
Impact of smoking of CV risk
A
dose related relationship —- more smoking — increase risk
—- 1 cig a day increase risk of stroke by 50%
— 1 hour hookah —— 100-200X smoke in 1 cig
— some evidence for 2nd prevention (extrapolate back that it may help reduce future events)
21
Q
Benefits of quitting smoking on CV health
A
50% RRR of CVD
35% RRR of mortality (decrease risk by 1/3)
increase LE by 10 yrs
22
Q
T or F: if a trial improved LDL, it will improved clinical outcomes (ex// stroke)
A
F- not always
—- surrogate markers (such as LDL) have been shown to not always represent clinical outcomes
- have had drugs that improve LDL but not clinical outcomes
LDL can be surrogate for potency IF intervention has impact on clinical outcomes (its how LDL is decreased that makes a difference)
main surrogates looked at: LDL, HDL, TG
23
Q
Which drugs have the largest impact on HDL levels
A
niacin + fibrates (15-35%)
24
Q
Which drugs have the largest impact on TG levels
A
niacin’s + fibrates (20-50%)
25
Which drugs decrease LDL the most
PCSK9 inhibitors — decrease by 50-70%
26
MoA of statins
inhibit HMG CoA reductase —- decrease production of cholesterol in liver —- hopefully increase LDL R expression + take in more LDL (increase Cl)
27
T or F: most of the CV benefit of statins is though to come from its impact on HMG CoA reductase
F - thought to be a result of pleiotropic/extra effects
- improvement in endo fxn
- inhibition of inflammatory response
- antithrombotic effects
- increase in NO
- antioxidant properties
- stabilization of plaque
28
Which statins are metabolized by CYP3A4
Lovastatin, simvastatin , atorvastatin
SAL
29
Which statins are hydrophilic
rosuvastatin
30
Which statins have longer t1/2
Atorvastatin + rosuvastatin
( 15-30hrs)
31
MDD of atorvastatin + rosuvastatin
A - 80mg
R - 40mg
S- 80mg
32
T or F: most statins are excreted in poop
T
33
Which statins are metabolized by CYP2C9
Fluvastatin
34
What drugs are inducers + inhibitors of CYP3A4
Inhibitors: diltiazem, verapamil, erythromycin, ketoconazole (decrease CL)
inducer: phenytoin, rifampicin, dexamethasone (increase Cl)
35
How much does low intensity statins lower LDL ? Moderate? High?
low: < 30% reduction
moderate - 30-50%
high > 50% reduction
36
What statins are considered high intensity ?
Rosuvastatin 20-40
Atorvastatin 40-80mg
** sometimes simvastatin 80mg
intermediate intensity
—- rosuvastatin 5-10
—- atorvastatin 10-20
37
For primary prevention of CVD, what intensity of statin should I use
low-moderate (rosuvastatin 5-10 or atorvastatin 10-20)
— no need to ToT
38
What dose /intensity of statin should be used for 2nd prevention
evidence for higher intensity (still no ToT)
—- don’t monitor LDL for efficacy
39
T or F: for atorvastatin + rosuvastatin, you must dose at night
F- longer t1/2 so can dose in AM or HS
—- short t1/2 drugs must be doses at HS
40
What is the acronym to remember SEs of statins
HMG
- hepatic
- muscle
-GI
41
T or F: prevalence of hepatotoxicity increases with dose
T- dose dependent increase in hepatic enzymes (0.5-2%)
progression to LF is fare, reversal common with decrease in dose
42
What to do if pt experiences hepatotoxicity from a statin
rechallenge, decrease dose, or change statins
43
T or F: statins can make fatty liver disease better
T- there is some evidence that it may help’
—- Cholestasis + liver disease are listed as CI but no evidence that they make it worse
44
What to monitor when looking for hepatotoxicity with statins
get baseline ALT/AST—- check in 3mths after starting therapy (if increase —- decrease dose or change statin
— check annually going forward
45
What is myalgia
muscle pain/weakness with no CK increase
46
What is myositis
muscle symptoms + increase in CK
47
What is rhabdo
muscle symptoms + big increase in CK (>/=10X UL)
— pee may turn brown due to myoglobin
48
How come is myalgia + myositis with statin use
0.12% get
49
What is the thought MoA for myopathy with statins
Coenzyme Q10 ??
50
RF for statin induced myopathy
> 80, F, lower DMI, DM, kidney/liver diseases, untreated hypo, trauma, surgery, intense exercise
Drugs: DIs (fibrates, NA, CCB, amiodarone)
51
T or F; when starting statins, you should always check CK
F- only order CK when have symptoms
—- can assess muscle symptoms at 6-12 wks after starting therapy
52
Management options for myopathy induced by statins
reduce dose, switch statins, try not daily dosing, try other agents or Q10 supplements
53
What did the ASCOT LLA trial show for statins
POP: HTN pts 40-79 w/ 3 other RF (primary prevention)
Looked at hard outcomes
Drug: atorvastatin 10mg (I)
Result: intermediate statins used in primary prevention in HTN pts 40+ with other CVD RF —- decrease outcomes by 25%
54
T or F: regardless of pt traits (age, sex, baseline lipids, CV risk, other RF), statins always result in a reduction in risk by 25%
yes - RRR independent of pt’s baseline risk while ARR + NNT are dependent
55
What did the Treat to Target study show
looked at ToT vs high intensity statins in 2nd prevention (CAD)
pop: people with CAD (2nd prevention)
I: statin therapy w/ titrating dose to reach LDL target vs R20 or A40 (high intensity)
O: death, MI, stroke, coronary revascularization
Result: non inferior
—- fixed vs TOT —- same end impact in 2nd prevention
— fixed dose is no different in regards to SEs
56
T or F: use of statins in primary prevention, can help decrease incidence of DM
F- statins don’t increaes or decrease incidence (previous studies showed it increased risk of DM in 2nd prevention)
57
T or F: for 2nd prevention, it makes no difference whether you used fixed dose or titrate up dose
T
58
Impact of statin use in primary prevention on DM incidence
No impact
— was though to maybe increase incidence (B> R)
59
T or F: must studies in primary prevention look at high intensity statins
F- most are moderate to low
—- trials that compare different statins are underpowered (none comparing them on primary prevention)
60
Which study use high dose statin in primary prevention
Jupiter 20mg Rosuvastatin
—- ACSCOT LLA — atorvastatin 10mg (M)
61
T or F: unlike in 2nd prevention, in primary prevention, there is evidence for the benefit of ToT approach
F - no evidence for high intensity OR ToT in primary
62
When is the only time we have evidence for high intensity statins
secondary prevention
63
Which 2 drugs were studied in the pre statin era
Gemfibrozil
Cholestryamine
64
Other than statins, which other drugs have evidence for monotherapy in primary prevention
gemfibrozil
cholestyramine
65
What drugs are fibrates + main impact on surrogate markers
Bezafibrate, fenofibrate + gemfibrozil
— lower TG (really good at) + raise HDL + some impact on LD (variable )
66
T or F: evidence for combo of fenofibrate w/ statin but not a statin with gemfibrozil
T
gemfibrozil : can’t be combine w/ statin (SE risk) + only evidence as monotherapy
67
When are fibrates considered 1st line
treatment of severe high TG (>/=10)
—- use to help prevent acute pancreatitis
68
What is the Helsinki Heart Study and what did it show?
determined gemfibrozil efficacy
Pop: men w/out CVD + non HDL > 5.2 (primary); a higher percent were smokers 25%
looked at gem vs placebo + impact on fatal/nonfatal MI + sudden cardiac death
—— decreased by 20-30% but had moderate-severe GI symptoms
Summary: can be considered as alternative to statin in primary prevention if not tolerated
69
Field trial
fenofibrate + DM
—- showed to reduce nonfatal MI + coronary revascularization in T2DM (no impact on fatal events though)
*** generally don’t use with statins unless high TG + low HDL
70
MoA of BA resins
decrease cholesterol A from GI
efficacy: decrease LDL a little bit + increase HDL
71
What does the LRC CPPT trial show
cholestyramine improved CV outcomes
pop: men 35-59, w/out CVD + total cholesterol > 6.8
Outcome: non fatal MI + CHD death
results: no real impact on mortality but did improve CHD death/MI composite
*** A LOt OF GI SEs
72
Admin instructions for. BA Resins
mix with water/juice, take with meals
- normally BID but can be up to 6 times daily (MDD 24g)
- don’t sip —- tooth discolouration
** can impact A of other drugs + fat soluble vitamins
73
What indication does ezetimibe have (not evidence , just what do guidelines say we can use it for(?
mono therapy (alt to statin) or in combo with statins (primary or secondary
74
What is the only thing we have evidence for when it comes to ezetimibe
benefit of use as an add on therapy in secondary prevention
75
MoA: of ezetimibe
inhibit intestinal A of cholesterol from diet
76
T or F: ezetimibe has been shown to improve clinical outcomes
F- approved for use based on surrogate markers only (LDL reduction + CIMT — how thick the carotid is)
—- CIMT thought to be huge predictor of future CVD events , but drugs that change it —- don’t impact CV outcomes
77
What did the IMPROVE-IT study show
pop: pts with ACS in past 10 days (2nd)
Compared intermediate statin + E vs statin by itself (SHOULD BE HIGH INTENSITY)
outcome: nonfatal MI or nonfatal stroke, CHD
results: decrease in primary outcomes (2nd prevention)
78
Bottom line for ezetimibe use
no evidence for primary use: mono or add on
only evidence for add on in 2nd prevention (wrong statin dose used too )
79
What is PCSK9 and what does the PSCK9 inhibitor do
PCSK9: enzyme that binds to LDL R on liver cells + causes them to be degraded (increase LDL in periphery bc liver can’t take in)
inhibitor: blocks enzyme + prevents R degradation
different options
- monoclonal Ab : Rapatha (evolocumab) or Praluent (alirocumab)
OR inclisiran (siRNA not an Ab)
80
General PCSK9i admin instructions
SC
E+A: every 2wks or monthly
I : every 6 mths
—- best at lowering LDL (50%) BUT SUPER expensive + not covered
81
What do the Fourier (E) and ODYSSEY (A) studies show
PCK9i impact in 2nd prevention when pt already on max statin dose (add on)
Efficacy —- decreae MI + stroke (looked at MACE)
82
What is the indications of use for PCSK9 inhibitors
use in 2nd prevention (high risk) or primary prevention (FH / super super high risk—- no evidence) as add on therapy to statin
83
What is the ORION study
study that is in phase III trials RN ; looking at inclisiran
— approved to market based on surrogate markers (LDL decrease by 50%)
— ORION 4 still going on
84
Bottom line for PSCK9i
Indicated as ADD ON
- homo or hetero FH on max tolerated statin dose
- 2nd prevention : clinical CVD + max statin
- OFF label: high risk primary prevention pts on max statins
** not great evidence for it to be statin alternative
85
What are ANGPTL3 inhibitors
Evinacumab
ANGPTL3: protein that inhibits LPL (stops release of FFA)
- inhibition of enzyme increase TG breakdown + FFA release + Cl of VLDL
approved in Canada as homo FH ADD ON
—- Elipse HoFH: showed decrease in LDL (no clinical outcomes yet)
86
When is the use of Icosapent Ethyl use recommended
used to reduce CV risk in 2nd prevention pts OR primary prevention pt w/ DM + >/= 1 CV RF
—— both need to have fasting TG bw 1.5-5.6
—— need to be on max statin
CV RF
- men >/=55, W>/=65
- smoking (or in past 3 mths)
- HTN / BP meds
- hsCRP >3
eGFR < 30
retinopathy
micro or macro albuminuria
ABI < 0.9
87
What are considere
88
What are MTTP inhibtors
Lomitapide
Indication: add on for adult pts with homo FH (still in phase 3 trials)
— showed decrease in LDL , no impact on MACE yet
— risk of liver toxicity
89
90
T or F: Niacin is still recommended for use in dyslipidemia treatment
F- not great clinical outcomes
- slay on paper (great impact on surrogate): increase HDL, lower LDL, and decrease Lp (a)
** no evidence in primary prevention context + mixed info for 2nd
91
What is the AIM -HIGH Trial and what did it prove
study that looked at niacin w/ statin + 2nd prevention compared to statin
trial stopped early due to increaes ischemic stroke in treatment group ‘
92
What is the HPS2 Thrive Trial
study that looked at adults 5-80 w/ vascular disease
I: statin + niacin + lapropiant (to decrease N SEs) vs simvastatin
lapropriant: reduce flushing (prostaglandin D2 R1) but increased platelet aggregation
saw higher mortality in treatment group
93
What are all the Ses of niacin
increased infection, myopathy, liver issues, BG, hypotension
94
Bottom line for niacin
not recommended for most pts
—- may use in extremely high risk pt (FH ) who have high LDL despite max statins + other agent
** poorly tolerated; 80% flushing
95
What are CETP inhibitors
Not approved in Canada
—- trapibs
Accelerate trial (Evacetrapib)
- 2nd prevention (those with ACS within past year) , PAD, or DM + CAD
— showed to decrees LDL but no impact on CV
96
What are the ATP citrate lyase inhibitors
MoA: stop cholesterol production earlier in process compared to statins
— bempedoic acid (not in canada yet)
Approved for use in HeFH or established ASCVD in combo with max statins
97
What is the CLEAR CV trial
for ATP citrate lyase inhibitors
pop: pts w/ statin intolerance (on super low dose) + have or are at high CVD risk (1 or 2nd)
—- can be used w/ or without statins
results; decrease in MACE + LDL, no decrease in mortality
——- evidence for alternative to statin when can’t have statins + meet criteria for increased risk of primary prevention context
98
What is the criteria for high risk primary prevention for ATP citrate lyase inhibitor use
Reynolds score > 30% or score >7/5%
- coronary artery Ca score > 400
T1 or T2 DM > 65 (W) or > 60 (M)
99
What are the other combo evidence based therapies for primary prevention
statin + omega 3 FA (REDUCE-IT trial)
—- set population: DM, 1+ RF, TG 1.6-5.6 + on statin
