asteroid the effect of very high-intensity statin therapy on regression of coronary atherosclerosis...
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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
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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
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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
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Lumenarea
EEM area
Atheroma area
Ultrasound determination of atheroma area
Precise planimetry of EEM and lumen borderswith calculation of atheroma cross-sectional area
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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
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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
(%)
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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 (%)
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-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
†
†
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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% )
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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.
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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.).
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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.
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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
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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