2008调脂治疗进展与回顾

Primary outcome
AoV Replacement
Ischemic Events：SE（n=148）vs. P （n=187）p=0.02 Cancer occurrence: SE（n=105）vs. P （n=70）p=0.01
SEAS TRIAL
Simvastatin & Ezetimibe in Aortic Stenosis
Percentage change from baseline
10
0
10 20 30 40 50 60 70 0
LDL-C
Simva Eze-Simva
Baseline (mg/dL) 318 ± 66
319 ± 65
24 months (mg/dL) 193 ± 60
141 ± 53
P<0.01
• However, the effect of Ezetimibe on the progression of atherosclerosis is unknown
Kastelein, et al, N Eng J Med 358:1431-1443 April 3, 2008
ENHANCE Study Design
-16.5 % incremental reduction
6
12
18
24
Months
Simva Eze-Simva
Other Lipids and Apolipoproteins
Percent Change From Baseline
Simvastatin 80
EZE/simva 10/80
Total Cholesterol LDL-cholesterol Triglycerides (median)
ENHANCE TRIAL Simvastatin With or Without Ezetimibe in Familial Hypercholesterolemia
BACKGROUND
• Ezetimibe, a cholesterol-absorption inhibitor, reduces levels of LDL-c when added to statin treatment.
• Implications: Lipid lowing therapy can be used to reduce the risk of ischemic CV events. Cancer incidence needs to be further analyzed.
主要内容
• 新型调脂药胆固醇吸收抑制剂----ENHANCE、SEAS 带给 我们的思考
IMT assessment
-10 to -7 -6 Weeks
0
3
6
9
12
15 18 21 24
Months
ENHANCE cIMT Methodology Carotid Intima-Media thickness (cIMT) measurements
• Measurements were made at a predefined angle of insonation • Only the far-walls of all segments were imaged • Images were stored in DICOM for offline image analyses
• Implications: No need to prescribe statins in HF pts of no-ischemic etiology. MD discretion should be used on discontinuing statins in HF pts with ischemic etiology.
Pre-randomization Phase
R
A
N
D
FH:
O
LDL-c ≥ 210 mg/dL
M
I
Z
A
T
Screening and Placebo Lead- I
Fibrate
In/ Drug
O
Washout
Washout
N
Ezetimibe 10 mg-Simvastatin 80 mg Simvastatin 80 mg
主要内容
• 新型调脂药胆固醇吸收抑制剂----ENHANCE、 SEAS TRIAL带给我们的思考
• 他汀能否改善慢性心力衰竭患者预后? • 他汀多途径抗动脉粥样硬化—干预炎症反应 • 评估AS 风险的指标:替代终点 or/and 临床终点? • LDL-C----抗AS首要干预目标 • 依托循证，重返他汀时代
-31.9±0.8 -39.1±0.9
-23.2
-45.3±0.8 -55.6±0.9
-29.8

HDL-cholesterol Apo B Apo A1
7.8±0.9 -33.1±0.9 6.9±0.8
10.2±1.0 -46.7±0.9 6.3±0.8
P value <0.01 <0.01 <0.01 0.05 <0.01 0.56
0.80 0.75 0.70 0.65 0.60
P=0.88
6
12
18
24
Months
Simva
Eze-Simva
ENHANCE TRIAL
Conclusion:
The addition of Ezetimibe to Simvastatin did lead to expected changes in LDL-C and hsCRP, but did not reduce any cIMT parameter The reasons for this discrepancy currently remains unknown
• PURPOSE: To investigate the impact of rosuvastation in HF pts.
The GISSI-HF TRIAL
Effects of rosuvastatin in patients with symptomatic chronic HF
• DESIGN: Prospective, multicenter, randomized, double blind, placebo controlled study of 4,574 patients with symptomatic HF of any etiology & any level of LVEF randomized to: Rosuvastatin (Rosu) 10mg po daily (n=2,285) & placebo (n=2,289). Median follow-up=3.9 yrs.
-26 % incremental
-40
reduction
-50
-60
-70
-80
3
6
12
18
24
Months
Simva Eze-Simva
Mean cIMT during 24 months of therapy
Longitudinal, repeated measures analysis
Mean IMT (mm)
• Primary Endpoint: All Cause Mortality • Secondary Endpoint: All Cause Mortality or
hospitalization for CV reasons.
Presented at ESC 2008/Gianni Tognoni MD
• PURPOSE: To determine the effects of long term intensive cholesterol lowing on AoVS.
• DESIGN: Randomized, double blind study of 1,873 patients with mild moderate, asympomatic aortic stenosis randomized to: 40mg simvastatin plus 10mg of ezetimibe(n=944) or placebo(n=929). Median follow up=52.2 months.
hsCRP
Median percent change from Baseline
Baseline
24 months
10
(mg/L)
(mg/L)
Simva
1.7(0.8-4.1)
1.2(0.6-2.4)
0
Eze-Simva
1.7(0.8-3-9)
0.9(0.5-1.9)
p < 0.01
-10
-20
-30
Hospitalization for CV Reasons
The GISSI-HF TRIAL
Effects of rosuvastatin in patients with symptomatic chronic HF
• Conclusion: Rosuvastation does not improve clinical outcomes in chronic HF pts of any age, etiology & systolic function level.
The GISSI-HF TRIAL
Effects of rosuvastatin in patients with symptomatic chronic HF
2288.8.8%%
28.1%
57.1%
56.1%
Probabillity of Death
All Cause Mortality
All Cause Mortality or
• Conclusion: Smivastatin/Ezetimibe therapy do not reduce combined AoV events & ischemic events in pts with AoVS; therapy did reduce the incidence of ischemic CV events.
• 他汀能否改善慢性心力衰竭患者预后? • 他汀多途径抗动脉粥样硬化—干预炎症反应 • 评估AS 风险的指标:替代终点 or/and 临床终点? • LDL-C----抗AS首要干预目标 • 依托循证，重返他汀时代
The GISSI-HF TRIAL
Effects of rosuvastatin in patients with symptomatic chronic HF
Rossebo NEJM 2008:359
SEAS TRIAL
Simvastatin & Ezetimibe in Aortic Stenosis
• Primary Endpoint: Composite of CV events: CV death; AoV replacement, nonfatal MI, hospitalization for HF,USA,CABG,PCI & non-hemorrhagic stroke.
SEAS TRIAL
Simvastatin & Ezetimibe in Aortic Stenosis
• BACKGROUND: Previous studies assessing the impact of statin therapy on aortic valve stenosis (AoVS) have demonstrated mixed results.
• BACKGROUND: Pleiotropic actions of statins may target components of the complex syndrome of HF. While observational studies, small RCTs etc, suggest a decrease in CV mortality in HF patients, large RCTs are needed.
• Secondary Endpoint: Events related to AoVS & ischemic CV events
SEAS TRIAL
Simvastatin & Ezetimibe in Aortic Stenosis
28.8% 35.3%
38.2%
28.3% 29.9%
Percent