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ASTEROID
The Effect of Very High-Intensity Statin Therapyon Regression of Coronary Atherosclerosis
The Effect of Very High-Intensity Statin Therapyon Regression of Coronary Atherosclerosis
Pr Jacques PUEL C.H.U. de Rangueil, Toulouse
Service de CardiologieVice-président de la SFC
Investigateur français de l’étude ASTEROID
Diapositives extraites de la présentation de S NISSEN - ACC 2006
Prior coronary IVUS progression trials
-1.2
-0.6
0
0.6
1.2
1.8
50 60 70 80 90 100 110 120
Medianchange
in atheromavolume
(%)
Mean LDL-C (mg/dL)
REVERSALpravastatin
REVERSALatorvastatin
CAMELOTplacebo
A-Plusplacebo
ACTIVATEplacebo
Relationship between LDL-C and progression rate
Unexplored region
1183 patients screened and 507 patients treatedat 53 centers in US, Canada, Europe and Australia
Rosuvastatin 40 mg for 24 months
Follow-up IVUS of originally imaged “target” vessel (n=349)
Intravascular ultrasound with 40 MHz transducerMotorized pullback at 0.5 mm/sec through >40 mm
length of single “target” coronary artery
158 patients withdrew or did not have an evaluable
final IVUS
Lumenarea
EEM area
Atheroma area
Ultrasound determination of atheroma area
Precise planimetry of EEM and lumen borderswith calculation of atheroma cross-sectional area
Lipid values and percent change (n=349)
Mean baseline
During treatment*
Percent change†
p value
Total cholesterol (mg/dL)
204 133.8 -33.8 <0.001
LDL-C (mg/dL)
130.4 60.8 -53.2 <0.001
HDL-C (mg/dL)
43.1 49.0 +14.7 <0.001
Triglycerides (mg/dL)
152.2 121.2 -14.5 <0.001
LDL-C/HDL-C ratio
3.2 1.3 -58.5 <0.001
* Time-weighted average† From least square mean
Dual primary IVUS efficacy parameters
-0.79
-1
-0.75
-0.5
-0.25
0
-5.6
-8
-6
-4
-2
0
Median change in percentatheroma volume
Median change in most diseased subsegment
Regressionp<0.001*
*Wilcoxon signed rank test for comparison with baseline
Regressionp<0.001*
Changein
atheromavolume(mm3)
Changein
atheromavolume
(%)
Distribution: Percent atheroma volume
0
20
40
60
80
-7 -6 -5 -4 -3 -2 -1 0 1 2 3 4 5
Numberof
patients
Regression63.6%
Progression36.4%
Change in percent atheroma volume (%)
-1.1
-0.6
-0.9
-0.3
-0.2
-0.9
-0.7
-1.25
-1
-0.75
-0.5
-0.25
0
Change in atheroma volume Subgroups: On-treatment lipid levels
Change in atheroma volume Subgroups: On-treatment lipid levels
*p<0.001 for change from baseline (regression)
LDL-C≤ mean(n=192)
LDL-C> mean(n=157)
HDL-C≤ mean(n=197)
HDL-C> mean(n=152)
Changein
atheromavolume
(%)
LDL-C< 70
(n=254)
LDL-C70-100 (n=78)
LDL-C≥100 (n=17)
*
*
* *
*
† p=NS for change from baseline
†
†
Adverse events: Safety population (n=507)
Major treatment-emergent adverse events
Death 4 (0.8% )
Myocardial infarction 10 (2.0% )
Stroke 3 (0.6% )
Central laboratory abnormalities
ALT > 3 x ULN 9 (1.8% )
ALT > 3 x ULN on two consecutive visits 1 (0.2% )
CK > 5 x ULN 6 (1.2% )
CK > 5 x ULN on two consecutive visits 1 (0.2% )
CK > 10 x ULN 0 (0.0% )
Conclusions I
• Very intensive treatment with rosuvastatin 40 mg in statin-naïve patients with CAD reduced LDL-C to 60.8 mg/dL and raised HDL-C by 14.7%.
• This regimen resulted in significant regressionfor all three primary and secondary IVUS efficacy parameters (p<0.001).
• Regression occurred in 64% to 78% of subjects treated, depending on the efficacy parameter.
• Regression was observed in subgroups including men and women, older and younger patients,and those with LDL-C above and below the mean.
Limitations
• ASTEROID explore des coronaires athéromateuses mais ne considère pas les lésions athéroscléreuses vulnérables et instables ayant provoqué ou étant susceptible de provoquer un syndrome coronarien aigu.
• L’étude n’aborde pas les résultats biologiques concernant les marqueurs d’inflammation (CRP, cholestérol LDL etc.).
Conclusions II
• The adverse events observed with this regimenwere low and typical of other high-intensity statin trials.
• The relative importance of LDL-C reduction and HDL-C elevation in producing these results will require further investigation.
• Maximally intensive statin treatment seems warranted in high-risk CAD patients.
• Rather than a fixed LDL-C goal, these findings suggest attaining the lowest levels of LDL-C achievable without adverse effects may be the optimal strategy.
Prise en charge thérapeutique du patient à haut risque cardiovasculaire
Prise en charge thérapeutique du patient à haut risque cardiovasculaire
Recommandations. Afssaps, mars 2005.
** Diabète de type 2 à haut risque• atteinte rénale,• ou au moins deux des facteurs de risque suivants : âge, antécédents familiaux de maladie coronaire précoce, tabagisme,hypertension artérielle, HDL-cholestérol< 0,40 g/l, microalbuminurie (> 30 mg/24 h)
Patient à haut risque cardiovasculaire :- Antécédents de maladie cardiovasculaire avérée- Diabète de type 2 à haut risque**- Risque de survenue d’un événement coronarien dans les 10 ans ≥ 20%
Objectif thérapeutiqueLDL-cholestérol < 1,0 g/l
Recent coronary IVUS progression trials
-1.2
-0.6
0
0.6
1.2
1.8
50 60 70 80 90 100 110 120
Medianchange
inatheromavolume
(%)
Mean low-density lipoprotein cholesterol (mg/dL)
REVERSALpravastatin
REVERSALatorvastatin
CAMELOTplacebo
A-Plusplacebo
ACTIVATEplacebo
Relationship between LDL-C and progression rate
ASTEROIDrosuvastatin
r2= 0.95p<0.001
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