Disclosures
Voor bijeenkomst mogelijk relevante relaties:
• Sponsoring of onderzoeksgeld
ZonMw,Wellerdieck-deGoedefonds,Leatarefounda8on,VriendenUMCUtrecht,NederlandseHarts8ch8ng
• Honorarium of andere (financiële) vergoeding
Geen
• Aandeelhouder
Nee
• Andere relatie, namelijk …
Fase II/III klinisch onderzoek met vrijwel alle denkbare lipiden-verlagende middelen (o.a. Sanofi, Medicines Company, Amgen, Pfizer, Eli Lilly, Merck, ISIS) Lidrichtlijncommissies:CVRM,addendumCVRMbijouderen,addendum(erfelijke)dyslipidemie
PCSK9; how it started
Affected family members with: • Total cholesterol >90th percentile • Tendon xanthomas • CHD, early MI, Stroke
Nat Genet 2003;34:154-156
GLAGOV trial
Up to 4-week lipid stabilization
period
Assigned to background
statin therapy
Placebo SC every month
Ran
dom
izat
ion
1:1
to s
tudy
dru
g
End
Of S
tudy
Maximum 6 weeks D1 W4 W12 W24 W36 W52 W64 W76 W78 W80 EOS
Study drug was administered monthly at home or in the clinic
Study visits:
Screening and placebo run-in period
• Clinically indicated coronary angiogram
• IVUS based on coronary angiogram results
• SC injection of 3 mL placebo
2–4 weeks
Last dose of
study drug
Last IVUS
procedure
Evolocumab 420 mg SC
every month
JAMA 2016;316:2373-2384
Intravascular Ultrasound (IVUS)
Leading edge of the EEM
Leading edge of the lumen
PAV = Σ(EEMarea – lumenarea)Σ(EEMarea) 100X
JAMA 2016;316:2373-2384
Robinson JG et al, NEJM 2015;372:1489-1499
Efficacy and safety of alirocumab in reducing lipids and cardiovascular events
(ODYSSEY LONG TERM study)
Robinson JG et al, NEJM 2015;372:1489-1499
Efficacy and safety of alirocumab in reducing lipids and cardiovascular events
(ODYSSEY LONG TERM study)
Recommendations Class Level
Prescribe statin up to the highest recommended dose or highest tolerable dose to reach the goal. I A
In the case of statin intolerance, ezetimibe or bile acid sequestrants, or these combined, should be considered. IIa C
If the goal is not reached, statin combination with a cholesterol absorption inhibitor should be considered. IIa B
If the goal is not reached, statin combination with a bile acid sequestrant may be considered. IIb C
In patients at very high-risk, with persistent high LDL-C despite treatment with maximal tolerated statin dose, in combination with ezetimibe or in patients with statin intolerance, a PCSK9 inhibitor may be considered.
IIb C
ESC guidelines on cardiovascular disease prevention: lipid-lowering therapy
Eur Heart J 2016;37:2315-2381
• PCSK9-remmingverlaagtLDL-cenverlaagtCVrisicoin2grotetrials>50.000pa8enten
• FOURIERresultatenbeves8gingen/ondersteunendebestaandevergoedingvoorPCSK9-i.
• NieuwemanierenvanPCSK9(endusLDL-c)verlaginginaantochtWelkepa8ëntenkomenm.i.metnameinaanmerkingvoor(verdere)LDL-creduc8emetPCSK9-i:
• pa8ëntenmetprogressievanvaatlijdenondanksop8malelipiden-behandeling.
• hoogrisicopa8ënten(bv.DM2,FH)dievaatlijdenontwikkelenondanksop8malelipiden-behandelingOFvaatlijdenhebbenenstreefwaardevanLDL-cniethalen.
• pa8ëntenmet‘cholesterol-ziekte’(FH)diestreefwaardevoorLDL-c(ruim)niethalen
Conclusies