complicated dyslipidemia: beyond first line therapy · managing the complicated dyslipidemia...
TRANSCRIPT
1
Managing the Complicated
Dyslipidemia Patient:
Beyond First-Line Therapy
Patrick Curtin, PharmD, BCPS
Clinical Coordinator Overlook Medical Center
Summit, NJ
Faculty Information
Presenter:
Patrick Curtin, PharmD, BCPS
Clinical Coordinator
Overlook Medical Center
Summit, NJ
Moderator:
David Heckard
Senior Director of Education
Pharmacy Times Office of CPE
Plainsboro, NJ
Disclosures
Patrick Curtin, PharmD, BCPS, has no financial relationships with commercial interests to disclose.
Pharmacy Times Office of Continuing Professional Education Planning Staff—Judy V. Lum, MPA, Elena Beyzarov, PharmD, David Heckard, and Donna W. Fausak—have no financial relationships with commercial interests to disclose.
PTOCPE uses an anonymous peer reviewer as part of content validation and conflict resolution. The peer reviewer has no relevant financial relationships with commercial interests to disclose.
The contents of this webinar may include information regarding the use of products that may be inconsistent with or outside the approved labeling for these products in the United States. Pharmacists should note that the use of these products outside current approved labeling is considered experimental and are advised to consult prescribing information for these products.
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Learning Objectives
Review current national guidelines on management of dyslipidemia and discuss emerging lipid goals
Describe the complicated dyslipidemia patient, focusing on refractory familial hyperlipidemia and statin intolerance
Examine strategies for achieving goal lipid levels in patients with familial hyperlipidemia
Discuss clinical aspects and mechanisms of statin-associated adverse effects and strategies for managing statin intolerance
Outline counseling strategies to optimize patient outcomes in management of dyslipidemia
Managing the Complicated
Dyslipidemia Patient:
Beyond First-Line Therapy
Patrick Curtin, PharmD, BCPS
Clinical Coordinator Overlook Medical Center
Summit, NJ
2
Initial Goals for CHD Risk Reduction
Identify Cardiovascular Risk
Patient Risk Factors
Smoking
Hypertension
HDL<40 mg/dL
Family history of premature CHD (1st-degree relative with CHD in male <55 y or female <65 y),
Age (male ≥45 y, female ≥55 y)
Define cholesterol goals
Optimize non-drug therapy/modify risk factors
Physical activity
Diet
Smoking cessation
Jellinger et al. Endocr Pract. 2012;18(suppl 1):1-78
Patient Counseling Point
Counsel patient on risk (Framingham Heart Score, Reynolds Score)
35-year-old male smoker, TC 230 mg/dL,
HDL 45 mg/dL with no other comorbidities
Framingham Score: 10% 1% (if quit smoking)
55-year-old male smoker, TC 220 mg/dL,
HDL 40 mg/dL with HTN (SBP 150/95)
Framingham Score: 26% 9% if patient quits smoking, controls blood pressure, and lowers TC to 190 mg/dL
http://hp2010.nhlbihin.net/atpiii/calculator.asp
American Academy of Clinical
Endocrinologists (AACE): 2012 LDL-C Goals
(mg/dL)
HDL-C Classifications
(mg/dL)
Triglycerides
(mg/dL)
High-risk: Established CVD or DM
+ 1 risk factor:
<100 or 70 (optional)
High-risk:
<40 (men)
<50 (women)
High-risk:
200-499*(high)
≥ 500 (very high)
Moderately high-risk: ≥2 risk
factors and 10-year risk >20% or
CHD equivalent
<100
Borderline:
40-59 (men)
50-59 (women)
Borderline:
150-199
Moderately high-risk: ≥2 risk
factors and 10-year risk ≤20%:
<130
Optimal:
≥ 60 (negative risk
factor)
Optimal:
<150
Low-risk: ≤1 risk factors:
<160
Jellinger et al. Endocr Pract. 2012;18(suppl 1):1-78
*Patients with triglycerides of 200-499 mg/dL should have a non-HDL goal 30 mg/dL higher than the LDL goal.
Cornerstone of Drug
Therapy
STATINS
Number Needed to
Treat 24 42 91 63 95
Mean baseline LDL (mg/dL) 150 192 134 118 108
10.9%
7.9%
3.0%
4.6%
2.8%
6.8% 5.5%
1.9% 3.0%
1.6%
0%
2%
4%
6%
8%
10%
12%
Percentage of Major
CHD Events
Placebo Statin
Efficacy of Statins for Primary Prevention
JAMA. 1998;279:1615-1622.
N Engl J Med. 1995;333:1301-1307.
Lancet. 2003;361:1149-1158.
Lancet. 2004;364:685-696.
N Engl J Med. 2008;359:2195-2207.
28.0%
13.2%
15.9%
11.8%
19.4%
10.2% 12.3%
8.7%
0%
5%
10%
15%
20%
25%
30%
4S Care Lipid HPS
Percentage of Major
CHD Events
Placebo Statin
Number Needed to
Treat 11 33 28 32
Mean Baseline LDL (mg/dL) 190 139 150 129
Efficacy of Statins for Secondary
Prevention
Lancet. 1994;344:1383-1389.
N Engl J Med. 1996;335:1001-1009.
N Engl J Med. 1998;339:1349-1357.
Lancet. 2002;360:7-22.
3
Intensive LDL Lowering in Secondary
Prevention
Treatment
Regimens
Atorva 80 mg
Prava 40 mg
Simva 80 mg
Simva 20 mg
Atorva 80 mg
Atorva 20 mg
Atorva 80 mg
Atorva 10 mg
Mean LDL achieved
(mg/dL) 62 vs 95 66 vs 81 80 vs 100 77 vs 101
26.3%
16.7%
10.4% 10.9%
22.4%
14.4%
9.3% 8.7%
0%
5%
10%
15%
20%
25%
30%
PROVE-IT A to Z IDEAL TNT
Percentage of Major CHD
Events
Low Dose Statin
High Dose Statin
P=0.14
P=0.07
N Engl J Med. 2004;350:1495-504.
JAMA. 2004;292:1307-1316.
JAMA. 2005;294:2437-2445.
N Engl J Med. 2005;352.
LDL Reduction with Statins
Statin LDL-C Reduction
Rosuvastatin 45%-55%
Atorvastatin 37%-51%
Simvastatin 28%-46%
Lovastatin 29%-48%
Pravastatin 20%-30%
Fluvastatin 17%-23%
Jones et al. Am J Cardiol. 2003;92(2):152-160.
What do we do after statins?
ASSESS COMPLIANCE!
Unique Challenges in
Hyperlipidemia
Patients intolerant to statins
Familial hyperlipidemia
Familial Hyperlipidemia (FH) Generally results in LDL >190 mg/dL
Risk of premature CHD is elevated 20-fold without treatment
Mostly caused from mutations in LDL receptor (LDLR) genes (chromosome 19) Results in loss of LDLR function, or loss of LDLRs
85%-90% of all FH
Hopkins et al. J Clin Lipidol. 2011;5(3 suppl):S9-S17.
Five Key Disorders of Familial Dyslipidemia
Disorder Prevalence
Polygenic hypercholesterolemia 1/20
Familial combined hyperlipidemia 1/100
Heterozygous familial
hypercholesterolemia
1/500
Familial defective apolipoprotein B-100 1/1000
Homozygous familial
hypercholesterolemia
1/1,000,000
Circulation. 2002;106(25):3143-3421
4
Diagnosis of Familial
Hypercholesterolemia
Consider diagnosis for all adults (≥20 y) with LDL cholesterol ≥190 mg/dL
Collect family history of high cholesterol and heart disease in 1st-degree relatives in these patients
No gene mutation in 20% of clinically definite FH patients
Hopkins et al. J Clin Lipidol. 2011;5(3 suppl):S9-S17.
WHO Diagnostic Criteria for Familial
Hypercholesterolemia
Criteria Score
1st-degree relative with premature
CAD or LDL >95th percentile
1
1st-degree relative with tendon
xanthanoma with LDL-C >95th
percentile
2
Patient has premature CAD 2
Peripheral vascular disease 1
Tendon xanthanoma 6
Arcus cornealis <45 years 4
LDL >330 mg/dL 8
LDL 250-329 mg/dL 5
LDL 190-249 mg/dl 3
LDL 155-189 mg/dL 1
>8: Definite FH 6-8: Probable FH 3-5: Possible
WHO/HGN/FH/Cons/99.2. Geneva: WHO; 1999
Treatment Goals in FH
Patients diagnosed with FH should initiate therapy to reduce LDL ≥50%
ASAP Trial Atorvastatin 80 mg vs simvastatin 40 mg
54% LDL reduction vs 42% LDL reduction
Carotid intimal medial thickness (IMT) decreased in atorvastatin group vs increasing in simvastatin group
After switching simvastatin patients to atorvastatin, IMT arrested after 2 years of treatment
Further LDL lowering may be required to reach LDL-C goals
Robinson et al. J Clin Lipidol. 2011;5(suppl 3):S18-S29.
Patient Case
Ms. Graff is 21-year-old female presents to a local primary care
clinic for follow-up regarding family history of hyperlipidemia
LABS: WNL, except LDL: 360 mg/dL, HDL: 32 mg/dL
Medications: None
Smoking Habit: 1 pack/day
Family History:
Mother with heavily oxidized LDL >400 mg/dL, negative CAD
Father with MI at age 50
Brother without CAD, but recent LDL ~350 mg/dL
Uncle with severe hyperlipidemia and several MI’s
RX: Lovastatin 20 mg, ↑ to 80 mg
She presents 6 months later with LDL 220 mg/dL
Patient Case: Assessing the
Risk
Risk Factors: smoking, family history of CAD,
low HDL
Reynolds Score 8% risk
LDL goal: <130 mg/dL
Caveat: Many risk predictions scores are not
specific to familial hyperlipidemia. Risk of CHD
can be up to 20-fold in patients with FH.
Average LDL-C Decreases Required in FH
Baseline LDL-C
levels
190
mg/dL
220
mg/dL
250
mg/dL
280
mg/dL
310
mg/dL
To reach LDL-C <100 -32% -41% -48% -54% -58%
Civeira et al. J Clin Lipidol. 2011;5:59-517.
LDL Targets in FH
5
Non-Statin Options to reduce LDL-C
LDL-C HDL-C Triglycerides Comments
Statins
↓ 21%-55% ↑ 2%-10% ↓ 6%-30%
Fibrates ↓ 20%-25% ↑ 6%-18% ↓ 20%-35% Gemfibrozil
may increase
LDL 10%-15%
Bile Acid
Sequestrants
↓ 15%-25% No effect May increase Colesevelam ↓
HbA1c ~0.5%
Cholesterol
Absorption
Inhibitors
↓ 10%-25% No effect ↓ 2%
Niacin ↓ 10%-25% ↑ 10%-35% ↓ 20%-30%
Jellinger et al. Endocr Pract. 2012;18(suppl 1):1-78.
Ezetimibe (Zetia®)
Ezetimibe Metabolic Effects
Reduces LDL-C by 10%-25%
Results in additional LDL-C reductions of
23%-30% when added to statin therapy
Reduces LDL-C by an additional 20%-22%
when combined with fibrates
No morbidity/mortality data as monotherapy
Very well tolerated
Bays et al. Clin Ther. 2001;23:1209-1230.
Dujovne et al. Am J Cardiol. 2002;90:1084-1091.
Ezetimibe Combination Therapy
ENHANCE TRIAL
Pts with FH with an LDL
≥210 mg/dL
Simvastatin 80 mg plus
placebo or ezetimibe10 mg
Followed for 24 months
Primary Outcome;
Change in carotid artery
intimal medial thickness
Results: No difference with
addition of ezetimibe
N Engl J Med. 2008;358:1431-1443.
Limitations to ENHANCE
80% of participants had received long-term statin therapy prior to the trial
Did not address actual clinical outcomes
Ongoing trial, IMPROVE-IT, plans to be completed in 2013 to address clinical outcomes of ezetimibe added to simvastatin therapy
Toth et al. J Clin Lipidol. 2010;5:655-684.
6
SEAS Trial
Patients with aortic stenosis Simvastatin 40 mg plus
ezetimibe 10 mg or placebo
Excluded patients with CAD or DM
Mean LDL at baseline 140 mg/dL
LDL reduction ~50% in simvastatin/ezetimibe group
Rossebo et al. N Engl J Med. 2008;359:1343-1356.
0%5%
10%15%20%25%30%35%40%45%
CV Eve
nts
Ischem
ic Eve
nts
Cancer
Placebo
Simvastatin/Ezetimibe
SHARP TRIAL
Lancet. 2011;377:2181-2192.
Patients with chronic kidney disease
Simvastatin 20 mg plus ezetimibe 10 mg or placebo
Excluded patients with CAD or DM
Mean LDL at baseline 108 mg/dL
LDL reduction ~30% in simvastatin/ezetimibe group
No difference in cancer
Fibric Acid Derivatives
“Fibrates”
Fibrate Metabolic Effects
Fenofibrate, fenofibric Acid, and gemfibrozil
↑ HDL 6%-18%, ↓ TG 20%-35%,
↓ LDL 20%-25%
Gemfibrozil
May not change or even increase LDL in severe hypertriglyceridemia
Not indicated for FH, unless severely hypertriglyceridemic (FCH)
Cardiovascular benefit as monotherapy (VA-HIT, BIP, Helsinki Heart trials)
Jellinger et al. Endocr Pract. 2012;18(suppl 1):1-78.
Fibrate Combination Therapy
ACCORD Study
5518 patients with type 2 diabetes on simvastatin
Given fenofibrate or placebo
Mean LDL ~100 mg/dL
No difference in CV events
Subgroup analysis of patients with triglycerides
>204 mg/dL and HDL ≤ 34 mg/dL showed
reduction in CV events
N Engl J Med. 2010; 362:1563-1574.
Fibrate Adverse Effects and
Drug Interactions
Adverse Effects
Dyspepsia, upper GI complaints, gallstones, and
myopathy
Contraindicated in severe renal disease
Drug Interactions
Gemfibrozil ↑ concentration
Statins
Repaglinide, thiazolidinediones, and sulfonylureas
Warfarin (displaces protein-bound warfarin)
Fenofibrate safer with statins
7
Niacin
Niacin Metabolic Effects
Mortality benefit with monotherapy
↓ LDL 10%-25%, ↓ TG 20%-30%, ↑ HDL 10%-35%
Increases Blood Glucose Usually returns to baseline at 14-32 weeks
NOT a contraindication in diabetes
Flushing (up to 88% may experience) Diminishes with continued use
Discontinuation in clinical trials (~6%)
Less with extended-release niacin
Can pretreat with aspirin 325 mg
Jellinger et al. Endocr Pract. 2012;18(suppl 1):1-78.
Elam et al. JAMA. 2000;284:1263-1270. Grundy et al. Arch Intern Med. 2002;162:1568-1576.
Vittone et al. J Clin Lipidol. 2007;1:203-210. Canner et al. J Am Coll Cardiol. 1986;8:1245-1255.
Niacin Combination Therapy
HATS Study Simvastatin plus niacin in patients with CAD
Decreased LDL by 42% decreased CV events
Mean LDL 113 mg/dL
FATS Study Niacin + colestipol
Decreased LDL 32%, and decreased rates of CV events
HATS/FATS were small trials
HPS-2 THRIVE Ongoing Expected results 2013
Brown et al. N Engl J Med. 2001;345:1583–159.2 Am Heart J. 2011;161:538-543.
Niacin Combination Therapy
AIM-HIGH Trial
Niacin 1500-2000 mg/day or placebo in
addition to simvastatin 40-80 mg in patients
with CHD
LDL reduced from 74 mg/dL 62 mg/dL
No difference in CV events between groups HPS-2 THRIVE
Ongoing Expected results 2013
NEJM 2011; 365:2255-2267
Bile Acid Sequestrants
(BAS)
BAS Metabolic Effects
Demonstrated reduction in coronary events as monotherapy
Cholestyramine/colestipol/colesevelam
↓ LDL-C by 15%-25%, ↑ HDL by 4%-8%.
May increase triglycerides
Poorly tolerated GI side effects (~40% discontinuation rate) Colesevelam may be better tolerated
Jellinger et al. Endocr Pract. 2012;18(suppl 1):1-78.
Andrade et al. N Engl J Med. 1995;332:1125-1131. Prosbstfield and Rifkind. Eur J Clin Pharmacol. 1991;40:S69-S75.
8
Bile Acid Sequestrants
GLOWS Study
Colesevelam ↓ glucose (↓ HbA1c 0.5%)
January 2008FDA approval as an adjunct glucose-
lowering therapy for type 2 diabetes
FATS Study
Lovastatin + colestipol ↓ LDL 46%
Niacin + colestipol ↓ LDL 32%
Both groups had less arthrosclerosis progression
Both groups had lower rates of death, MI, or
revascularization
SMALL Study
Zieve et al. Clin Ther. 2007;29:74-83. Zhao et al. Am J Cardiol. 2009;104:1457-1464.
BAS Dosing and Adverse
Effects
Dosing Colesevelam: 1.875 g (3 tabs) BID or 3.75 g daily
Cholestyramine: 4 g 1-2x/day, increase monthly up to 16-24 g, as tolerated.
Colestipol: 2 g 1-2x/day, increase monthly by 2-4 g per day as tolerated to maximum 16 g
Adverse Effects Constipation, abdominal pain, bloating, nausea,
flatulence
Administer with food
BAS Drug Interactions
Drug Interactions: ↓absorption of many meds
Cholestyramine: Take other medications at least
1 hour prior and 4-6 hours after cholestyramine
Colesevelam:
Cyclosporine, glimepiride, glipizide, glyburide,
levothyroxine, olmesartan, OC’s should be taken at
least 4 hours prior to colesevelam
These are only known drug interactions; use caution
with all meds
Question
Ms. Graff presents on 80mg of Simvastatin
and an LDL of 220 mg/dl (goal 130mg/dl).
What should be the next step?
A. Access Diet
B. Change to higher potency statin
C. Add additional therapy.
D. All of the above
Patient Case
LDL 220 mg/dL on 80 mg lovastatin
Patient changed diet to vegetarian and quit
smoking
Atorvastatin 80 mg added along with
cholestyramine (titrated to 12 g BID)
LDL after 12 months116 mg/dL
Patient Case
Ms. Graff doing well; however, after 2 years
patient stops taking cholestyramine
secondary to poor palatability
LDL-C now 150 mg/dL (HDL 30 mg/dL)
What is our next step?
9
Question
What alternative for cholestyramine would be
best for Ms. Graff?
A. Colesevelam
B. Ezetimibe
C. Niacin
D. Gemfibrozil
Statin-Associated
Adverse Effects
Myopathy
Definitions
Myalgia: symptoms without creatine kinase (CK) elevations
Myositis: symptoms with CK elevations
Rhabdomyolysis: symptoms w/ CK elevations >10x normal
Rare: ~1/3400 pts will experience creatinine kinase elevations >10x or rhabdomyolysis
“Real-world” experience with higher incidence
PRIMO database muscle symptoms ~10% of patients
Can occur at any dose
More common with lipophilic statins (simvastatin/lovastatin)
Silva et al. Clin Ther. 2006;28:26-35.
Bruckert et al. Cardiovasc Drugs Ther. 2005;19:403-414.
Mechanisms of Myopathy
No one really knows
Coenzyme Q-10 deficiency
↓ mitochondrial respiratory function
Induced myocyte death through decrease
in isoprenoid production
Genetic variants on chromosome 12 that
affect statin blood levels
Arca et al. Diabetes Metab Syndr Obes. 2011;4:155-16.6
Liver Toxicity
AST/ALT elevations Transaminitis
Dose-related
Usually resolves within 4 weeks after discontinuation
More common with less lipophilic statins (pravastatin, rosuvastatin, atorvastatin, fluvastatin)
February 2012: FDA recommended removal of routine liver function test monitoring for all statins
Arca et al. Diabetes Metab Syndr Obes 2011; 4: 155-166
Dale et al. Am J Med. 2007; 120: 706-712
Management of Statin
Intolorance
Myositis and Transaminitis
10
Assess Possible Confounders
Statin-Induced Myopathy Hepatic Toxicity
High physical activity Acute viral disease
(hepatitis)
Heavy alcohol consumption Alcoholic liver disease
Drugs affecting statin
concentrations
- gemfibrozil, cyclosporine,
amiodarone, macrolides,
verapamil, fluconazole, HIV
medications
Grapefruit juice
Hypothyroidism
Major surgery
Arca et al. Diabetes Metab Syndr Obes. 2011;4:155-166.
Switching Statins
Hansen et al.
37 patients with statin-induced myositis changed statin
43% tolerated a new statin
Glueck et al.
61 patients with statin intolerance secondary to myalgias
Given rosuvastatin 5 mg or 10 mg per day
All patients except one tolerated therapy,
with LDL reductions ~40%.
Hansen et al. Arch Intern Med. 2005;165:2671-2676.
Glueck et al. Clin Ther. 2006;28:933-942.
Alternate-Day Statin Dosing
Trialed with several statin therapies
Most efficacious for statins with long half-life
Atorvastatin
T1/2:14 hr2 metabolites (T1/2 20-30 hr)
Metabolites contribute to 70% of activity
Rosuvastatin
T1/2: 19 hr
Arca et al. Diabetes Metab Syndr Obes. 2011;4:155-166.
Alternate-Day Dosing Trials
Regimen LDL-C Effect
Atorvastatin 10 mg QOD ↓ 30% after 8 weeks
Atorvastatin 20 mg/day
Atorvastatin 20 mg QOD
↓ 41 % after 3 months
↓ 36% at 1 month, ↓ 46% at 3 months
Atorvastatin 10 mg/day, then
10 mg QOD for 12 weeks
↓ 39% on daily regimen
↓ 23% after switching to QOD dosing
Rosuvastatin 5 mg M-W-F
Rosuvastatin 2.5 mg M-W-F
↓ 38% after 6 weeks
↓ 20% after 6 weeks
Rosuvastatin 2.5 mg to 20 mg once
weekly
↓ 23% after 4 months
Ezetimibe 10 mg/day, then add
atorvastatin 10 mg twice weekly
9% of patients achieved LDL goal on
ezetimibe alone vs 84% with the
combination
Piamsomboon et al. J Med Assoc Thai. 2002;85:297-300.
Keles et al. Anadolu Kardiyol Derg .2008;8:407-412.
Ferrer-Garcia et al. Acta Diabetol. 2006;43:75-78.
Mackie et al. Am J Cardiol. 2007;99:291.
Ruisinger et al. Am J Cardiol. 2009;103:393-394.
Management of Myalgias
Tolerable muscle pains and CK <5x ULN
Continue or reduce dosage
CK >5x ULN or intolerable
muscle pains
Discontinue statin. Restart when symptoms disappear at
lower dosage or different statin
If symptoms recur with multiple statins at low doses, start non-statin
lipid-lowering agents.
If symptoms recur, consider: - Rosuvastatin 2.5-5 mg daily
- Rosuvastatin 5-10 mg - Atorvastatin 10-20 mg every other day
Rhabdomyolysis
Consider risk-benefit of statin therapy
Arca et al. Diabetes Metab Syndr Obes. 2011;4:155-166.
Management of Transaminitis
AST/ALT <3x ULN
Continue statin, recheck in 6 months
Consider other causes (alcohol)
AST/ALT >3x ULN
Hold statin therapy
Consider other causes (viral, alcohol, other drugs)
Rechallenge when enzymes decrease.
Consider lower-dose statin or changing to another statin (simvastatin/lovastatin)
Arca et al. Diabetes Metab Syndr Obes. 2011;4:155-166.
11
Dietary Manipulation
Jenkins study showed specific dietary portfolio was equivalent to lovastatin 20 mg
<7% calories from saturated fat, < 200 mg cholesterol
Provided the following per 1000 kcal 1 g of plant sterol (enriched margerine)
9.8 g of viscous fibers (eggplant and okra)
21.4 g of soy protein (soy milk)
14 g of almonds
Both groups ↓ LDL ~30%
Jenkins et al. JAMA. 2003;290:502-510.
Dietary Recommendations:
2500 Kcal Diet
<7% of calories from saturated fat175 kcal (17g)
Transfat <1%25 kcal (1 g)
Cholesterol <200 mg/day
Total fat ~25%-35% of calories(75 g)
Soluble fiber 10-25 g per day Oat bran, oatmeal, beans, peas, rice bran, barley, citrus fruits,
strawberries
Plant stanols 2 g/day (inhibit cholesterol absorption) Nuts, legumes
Margarine spreads Smart Balance with Heart Right®, Promise Activ® light spread
Nutraceuticals
Red yeast rice
Natural monacolin Inhibits HMG-CoA reductase
LDL 13%-25%
1800-2400 mg BID
Others
Phytostanols, berberine
Questionable cardiovascular benefit
4th-line approaches
Arca et al. Diabetes Metab Syndr Obes. 2011;4:155-166.
Coenzyme Q-10
100 mg/day shown in one study to decrease pain severity by 40%
Studied in small populations (<20 patients)
Mostly anecdotal reports
Not supported by current guidelines
Caso et al. Am J Cardiol. 2007;99:1409-1412.
Other Statin Concerns
Memory loss/dementia
Some evidence statins improve dementia
Case reports of acute memory loss or feeling
“cloudy,” with reversibility upon stopping
Diabetes
Patients with risk factors for diabetes may be at
increased risk
Cardiovascular benefit likely outweighs any risk of
developing diabetes
http://www.fda.gov/Drugs/DrugSafety/ucm293101.htm
Ridker et al. Lancet. 2012;380:565-571.
ATP IV: Coming in 2013?
Fixed-dose statin? Forget about LDL?
Combination therapy
To achieve LDL <70 mg/dL?
Raising HDL
HPS-2 and IMPROVE-IT trials (awaiting results)
High-sensitivity C-reactive protein (hsCRP)
Other targets of lipid therapy
Apolipoprotein B level
12
Newly Approved Therapy:
Juxtapid® (Lomitapide)
FDA approval in December 2012 for
homozygous familial hypercholesterolemia
Microsomal triglyceride transport protein
inhibitor ↓ secretion of Apo-B lipoproteins
Studied in 29 patients on statin therapy, and
in most cases ezetimibe
LDL 339167 mg/dL
Available through REMS only (1-85Juxtapid)
Cuchel et al. Lancet. 2013;381:40-46.
Newly Approved Therapy:
Kynamro® (Mipomersen)
FDA approved for homozygous familial
hypercholesterolemia
Inhibits Apo-B production
200 mg SQ weekly
Decreases LDL ~25%
Available through special distribution
Patients must be monitored for hepatotoxicity
Thank You!