LOOKING TO FOURIER:

What do the trials tell us

about LDL lowering and
cardiovascular events?
 NICE –CG 181 Continuum of CVD
Risk and its treatment
Acute coronary Atorva 80mg
syndrome (ACS) (+ Eze 10mg)
Post MI/Angina
Atorva 80mg
Secondary
Other Atherosclerotic Prevention
Manifestations
Atorva 80mg

Subclinical
Atherosclerosis: Atorva 20+ mg
Type 2 diabetes Primary
Prevention Lifestyle then
Multiple RFs
QRISK>10% Atorva 20mg

Low
Lifestyle
Risk

Courtesy of CD Furberg.; modified to include NICE CG181

 GLAGOV: Mean On-Treatment
LDL-C vs. Change in PAV
Locally Weighted Polynomial
Change Percent Atheroma Volume (%)

Regression (LOESS) Plot with 95%

confidence limits

On-Treatment LDL-C (mg/dL)

C h a n g e in a t h e r o m a v o lu m e
IVUS studies:
Change in atheroma volume vs. LDL-C

REVERSAL- P

2.5

REVERSAL- A 1.5 f(x) = 0.7 ln(x) − 0.09

R² = 0.74

f(x) = 0 x² + 0.04 x + 0.72

R² = 0.39
f(x) = 0.03 x + 0.72
1
R² = 0.36

0.5

0
-70 -60 METEOR
-50 -40 -30 -20 -10 0 10 20

-0.5
GLAGOV-E SATURN- A
SATURN- R -1

-1.5
Change in LDL-C (%)
 Meta-analyses of CHD vs LDL-C and Incremental
effects of lipid drugs

Cholesterol Treatment Trialists; Lancet 2010; 376: 1670

Charland SL & Stanek EJ; Pharmacother 2014; 34 : 452
 IMPROVE –IT : Ezetimibe in statin-treated ACS

Lipids Events
20

10 4.20 1.35 1.10 2.46 P=0.002 P=0.01 p=0.95

Change (%)

(1.80)
0

-10

1.40
-20
p=0.01

-30 Secondary prevention; n= 18144

Cannon CP et al ; NEJM 2015; 372 : 2387

 Defining recommendations
Targets
Consistent with
epidemiology
Rare in clinical trials
Traditional output
Focused on single risk factor
Set on 50th centile
Requires multiple
monitoring
Drug-based
Consistent with trials
 Exception limits defined
Common trial design
Novel output
Focused on overall risk
Centile-independent
Minimal monitoring
required