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