SLIDE 16 PCSK9 Inhibitors: Substantial LDL Reductions
Lower LDL Higher LDL
- 45
- 90
- 24 studies, 10,159 patients
(mix of PCSK9 vs. placebo and PCSK9 vs. ezetimibe)
(95% CI -69.6% to -25.4%)
LDL reduction: -58.8% (95% CI -61.0% to -56.5%)
Navarese et al., Ann Int Med, 2015
PCSK9 Inhibitors: Moving from LDL reduction to event reduction
patients (mix of PCSK9 vs. placebo and PCSK9 vs. ezetimibe)
- Total mortality reduction:
0.53% down to 0.31% OR 0.48 (0.27-0.85)
Navarese et al., Ann Int Med, 2015
All cause mortality reduction
patients (mix of PCSK9 vs. placebo and PCSK9 vs. ezetimibe)
0.33% down to 0.19% OR 0.49 (0.23-1.07) Cardiovascular mortality reduction
patients (mix of PCSK9 vs. placebo and PCSK9 vs. ezetimibe)
1.00% down to 0.58% OR 0.49 (0.26-0.93) Myocardial infarction reduction
PCSK9 Inhibitors: Event Reductions
- N=4,465 patients from phase 2 or 3
trials
- Evolocumab + standard therapy vs.
standard therapy alone
- Primary outcome: composite CV
events
- Median follow-up 11 months
- LDL down 61% (120 to 48)
- CV events down from 2.18% to 0.95%
HR 0.47 (0.28-0.78)
Sabatineet al., New EnglJ Med, 2015
Evolocumab OSLER-1 and -2 Trials
- N=2,341 patients on maximized statin
and with LDL>70
- Alirocumab vs. placebo
- Primary outcome: 24 week LDL
- Secondary outcomes: long term LDL, CV
events
- LDL down 62% at 24 weeks, same at W78
- CV events down from 3.3% to 1.7%
HR 0.52 (0.31-0.90)
Alirocumab ODYSSEY Trial
Robinson et al., New EnglJ Med, 2015 CV events: death, myocardial infarction, unstable angina, coronary revascularization, stroke, transient ischemic attack, and heart failure CV events: death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke,
- r unstable angina requiring hospitalization
Adverse events: injection site reactions, myalgia, neurocognitive events, ophthalmologic events
PCSK9 Longer Follow up Results
- FOURIER Trial
- n=27,564 patients; already on mod-
high intensity statin, RCT of
- evolocumabvs. PBOinjection
- Median 2.2 years of follow up
- Primary endpoint: composite of CV
death, MI, CVA, revascularization, unstableangina
– 9.8% in evolocumabarm vs. 11.3% in placeboarm(HR0.85, 95%CI 0.79-0.92) – lower risk of non-fatal MI (RR 0.73, 95% CI 0.65-0.82) – lower risk of non-fatal stroke (RR 0.79, CI 0.66-0.95) – risk of CV death (RR 1.05, CI 0.88-1.25) – all-cause mortality (RR 1.04, CI 0.91-1.19)
- Reduced CV events but did not
reduce mortality
- ODYSSEY-OUTCOMES Trial
- n=18,924 patients; acute coronary
syndrome in past year, on high intensity or dose-maximized statin, and with LDL ≥70, non HDL ≥100, or apolipoprotein B ≥80 ; RCT of alirocumab SQ vs. PBO injection q2weeks
- Primary endpoint: composite of CHD
death, nonfatal MI, fatal/nonfatal CVA,
- r hospitalization from unstable angina
- Median 2.8 years follow up
– 9.5% in alirocumab group, 11.1% in PBO (HR 0.85, 95% CI 0.78-0.93) – All cause death 3.5% in alirocumab vs. 4.1% in PBO (HR 0.85, 95% CI 0.73-0.98)
- Reduced CV events and reduced
mortality
Sabatine, MS et al., New EnglJ Med, 2017 Schwartz, GG et al., New EnglJ Med, November 2018
