1. for patients with dyslipidemia & previous stroke/TIA
PCSK9 inhibitors
for patients with dyslipidemia & previous stroke/TIA
George Ntaios
University of Thessaly, Larissa/Greece

2. Disclosures
Honoraria/speaker fees/advisory board/research support: Boehringer-Ingelheim; Sanofi; Galenica; Elpen; Bayer; Winmedica; BMS/Pfizer; Amgen; Medtronic
Most relevant disclosure

3. Mechanism of PSCK9 function

4. Mechanism of PSCK9 function

5. Mechanism of PSCK9 function
Nielsen et al. Circulation 2015

6. Stein et al. Annu Rev Med 2014

7. PCSK9 mutation related to hypercholesterolemia
Abifadel et al. Nat Genet 2003

8. Stein et al. Annu Rev Med 2014

9. Loss-of-function PCSK9 mutation
“… an apparently healthy, fertile, normotensive, college-educated woman with normal liver and renal function tests who works as an aerobics instructor.”
Zhao et al. Am J Hum Gen 2006

10. Loss-of-function PCSK9 mutation
Hooper et al. Atherosclerosis 2007

11. Cohen et al. NEJM 2006

12. Cohen et al. NEJM 2006

13. Stein et al. Annu Rev Med 2014

15. Pharma race
Dadu et al. Nat Rev Cardiol 2014

17. Pharma race
Dadu et al. Nat Rev Cardiol 2014

18. PCSK9-inhibitors meta-analysis

19. PCSK9-inhibitors meta-analysis: LDL lowering
Navarese et al. Ann Intern Med 2014

20. PCSK9-inhibitors meta-analysis: CV Mortality
Navarese et al. Ann Intern Med 2014

21. PCSK9-inhibitors meta-analysis: Myocardial infarction
Navarese et al. Ann Intern Med 2014

22. LDL and outcomes: the lower, the better
Larosa et al. NEJM 2015

23. LDL and outcomes: the lower, the better
Amarenco et al. Lancet 2009

24. PCSK9-inhibitors meta-analysis: Serious adverse events
Navarese et al. Ann Intern Med 2014

25. Evolocumab - OSLER
Sabatine et al. NEJM 2015

26. Evolocumab - OSLER
NNT: 81
Sabatine et al. NEJM 2015

27. Evolocumab - FOURIER

28. Evolocumab - FOURIER Inclusion criteria Evolocumab SC n~13,750
Age 40–85 years
MI, stroke or PAD
Additional risk factors (1 major or 2 minor)
Optimal background lipid therapy (including effective dose of statin ± ezetimibe)
LDL-C ≥70 mg/dL or non-HDL-C ≥100 mg/dL
Evolocumab SC
n~13,750
Placebo SC
Randomisation 1:1
Sabatine et al. Am Heart Journal 2016

29. Evolocumab - FOURIER
Sabatine et al. Am Heart Journal 2016

30. Alirocumab – ODYSSEY LONG TERM

31. Alirocumab – ODYSSEY LONG TERM
Robinson et al. NEJM 2015

32. Alirocumab – ODYSSEY LONG TERM
Placebo
Alirocumab 3% 1% 2% 4%
HR: 0.52 (95%CI: )
1.7%
3.3%
NNT: 63
Robinson et al. NEJM 2015

33. Alirocumab – ODYSSEY OUTCOMES
Schwarz et al. Am Heart Journal 2014

34. There is always a “But…”
Country
Annual Cost (Evolocumab)
USA
14,100 $ UK
6780 $
Austria
7293 €
Finland
7825 €
September 2015

35. Cost-effectiveness
Kazi et al. JAMA 2016

36. Take-home messages Alirocumab & Evolocumab
Evolocumab might be more informative about stroke patients
Both drugs showed safety and efficacy
The results of the mega-trials are expected in 2017
Cost is an issue