1. Lipid guidelines one year later—no controversy, just lack of understanding
Neal S. Perlmutter, MD, FACC
Overlake Medical Clinics Cardiology
Washington ACC CVT Meeting
September 10, 2015

2. Highlights from 11/13 guidelines
Lifestyle modification efforts are unchanged
Emphasis is on therapies shown to prevent vascular events in clinical trials

3. Highest risk is: Clinical vascular disease (CAD, CVA, TIA, AAA)
LDL >190
DM with >7.5% ten year MI risk
Treatment is HIGH INTENSITY STATIN THERAPY: Atorva 40/80, Rosuva 20/40 (lowers LDL >50%)

4. For all >40 y/o, use risk calculator
CVRISK 2013 in smart phone app store
If no DM, treatment is either high or “moderate intensity statin therapy” if 10 year MI risk exceeds 7.5%. Therapy lowers LDL 30-50%.
If DM and risk<7.5%, use moderate intensity statin therapy.
Moderate intensity: ATORVA 10/20, ROSUVA 5/10, SIMVA 20/40, PRAVA 40/80, LOVA 40, FLUVA 80, PITAVA 2/4

5. Statins without proven benefit
PRAVA <40
SIMVA 10 OR LESS
LOVA 20 OR LESS

6. DIABETES is now included in risk calculator (no longer automatically high risk)
Family history, weight not included in risk calculator
Lifetime risk of MI is included
Adjusting RF on calculator can show benefit to patients

7. Age = biggest driver of benefit
Age “cutoff” >75 for primary prevention reflects selection of trials included, NOT that data don’t exist, NOR that benefit of treatment is any less
Age cutoff not present in secondary prevention population

8. TITRATION TO LIPID TARGETS IS NO LONGER RECOMMENDED, AND FOLLOW UP LIPIDS ARE NO LONGER REQUIRED

9. Arguments favoring f/u lipids:
Assess adherence
Assess response to therapy
Patient reinforcement
Since guidelines: possible role for addition of EZETIMIBE

10. Arguments against f/u lipids:
Encourages under-treatment in high risk patients.
Trials showing benefits all used high intensity statin therapy, and did not titrate
Low intensity statin therapy resulting in LDL <70 likely does not produce similar benefit
May encourage addition of second agents not proven to improve outcomes.

11. Role of coronary calcium score
Zero = no treatment
Non-zero = treatment (modifiable in advanced age)
CACS> for stress testing
No role for CACS in symptomatic patients

12. No role for advance lipid testing
=CLASS III = DON’T DO IT = BAD DOCTOR
Past potential role was for selection of niacin in some patients. N/A now given niacin trial results

13. NONSTATIN THERAPIES

14. EZETIMIBE—IMPROVE IT
18, 000 patients with ACS, moderate intensity therapy (SIMVA 40), randomized to addition of EZETIMIBE vs placebo
Proven reduction in hard CV events (the only non-statin therapy with such proof in the modern era)
Lipids not titrated
Likely to include in future guidelines; how to incorporate outside trial design not clear

15. NIACIN
No benefit/trend to harm in two large randomized outcome trials, despite “better lipids” (AIM HIGH, HPS2/THRIVE)
Still indicated for high TG, though if needed, fibrates generally a better choice

16. FIBRATES Outcome trials are negative Best for high TG
If used, generic fenofibrate 160 mg generally best. Avoid branded fenofibrate or gemfibrozil.

17. FISH OIL/VIT C AND E: negative trials
RED YEAST RICE = ultra low dose statin. Similar modest LDL lowering effect to eating Cheerios. Effect not likely to benefit CV events.
RESINS: no trials in modern era, using tolerable doses

18. Approach to myalgias
Diffuse, not localized. Persistent for several days.
r/o other causes.
?drug holiday, with daily symptom tracking, repeat challenge, office review
?aldolase
Try other statins before non-statins
r/o PMR

19. Approach to conspiracy theories
Statins and dementia (negative in trials) vs forgetfulness (anecdotes/tell us…)
Statins and diabetes: association/not cause and effect; benefits far exceed risks (50:1)
Statins and cancer (negative in virtually all trials) or long term harm (none)
Statins and LFTs (so uncommon; no monitoring without complaint)

20. Ongoing trials/new frontiers
REVEAL: anacetrapib + statin in CAD. CTEP inhibition to raise HDL and further lower LDL. At 3.5 years of follow up. Other CTEP inhibitor trials had negative outcomes, despite great lipids.
ODYSSEY: PCSK9 inhibition (alirocumab) + statin up to one year after ACS. STILL ENROLLING. Additional LDL lowering proven, trial looks at outcomes

21. Alirocumab (PRALUENT)
Recently approved (Regeneron/Sanofi) by FDA for either familial hypercholesterolemia, or known CAD with LDL lowering which is felt to be inadequate while on maximally tolerated statin therapy
PCSK9 inhibition
Lowers LDL an additional 46-47% in clinical trials, with sustained effect. Well tolerated.
Outcome study still enrolling
Dose is 75 mg subcut q 2 weeks, up to 150 mg q 2 weeks
$14,000+ per year; access through company service

22. Evolocumab (REPATHA) Another PCSK9 inhibitor
Approved by FDA panel, not yet by full FDA
AMGEN
Similar results in LDL lowering to alirocumab
Also no outcome studies published, but they are ongoing

23. Abridged summary:
Kearney J, Curfman G, Jarcho J: A pragmatic view of new cholesterol treatment guidelines, NEJM 370; 3, pp

24. QUESTIONS