ASTEROID The Effect of Very High-Intensity Statin Therapy on Regression of Coronary Atherosclerosis Pr  Jacques PUEL C.H.U. de Rangueil, Toulouse Service de Cardiologie Vice-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 Relationship between LDL-C and progression rate 1.8 CAMELOT placebo REVERSAL pravastatin 1.2 Median change in atheroma volume (%) ACTIVATE placebo 0.6 REVERSAL atorvastatin A-Plus placebo -0.6 Unexplored region -1.2 50 60 70 80 90 100 110 120 Mean LDL-C (mg/dL)

1183 patients screened and 507 patients treated at 53 centers in US, Canada, Europe and Australia Intravascular ultrasound with 40 MHz transducer Motorized pullback at 0.5 mm/sec through >40 mm length of single “target” coronary artery Rosuvastatin 40 mg for 24 months 158 patients withdrew or did not have an evaluable final IVUS Follow-up IVUS of originally imaged “target” vessel (n=349)

Ultrasound determination of atheroma area Precise planimetry of EEM and lumen borders with calculation of atheroma cross-sectional area EEM area Lumen area Atheroma area

Lipid values and percent change (n=349) † From least square mean * Time-weighted average

Dual primary IVUS efficacy parameters Median change in percent atheroma volume Median change in most diseased subsegment Change in atheroma volume (%) Change in atheroma volume (mm3) Regression p<0.001* Regression p<0.001* *Wilcoxon signed rank test for comparison with baseline

Distribution: Percent atheroma volume 80 Regression 63.6% Progression 36.4% 60 Number of patients 40 20 -7 -6 -5 -4 -3 -2 -1 1 2 3 4 5 Change in percent atheroma volume (%)

Change in atheroma volume Subgroups: On-treatment lipid levels † -0.25 -0.2 † -0.3 Change in atheroma volume (%) -0.5 * -0.6 * -0.75 -0.7 * * -0.9 -0.9 -1 * -1.1 -1.25 LDL-C ≤ mean (n=192) LDL-C > mean (n=157) LDL-C < 70 (n=254) LDL-C 70-100 (n=78) LDL-C ≥100 (n=17) HDL-C ≤ mean (n=197) HDL-C > mean (n=152) *p<0.001 for change from baseline (regression) † p=NS for change from baseline

Adverse events: Safety population (n=507)

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 regression for 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 regimen were 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 - 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 thérapeutique LDL-cholestérol < 1,0 g/l ** 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) Recommandations. Afssaps, mars 2005.

Recent coronary IVUS progression trials Relationship between LDL-C and progression rate 1.8 CAMELOT placebo REVERSAL pravastatin 1.2 Median change in atheroma volume (%) ACTIVATE placebo 0.6 REVERSAL atorvastatin A-Plus placebo r2= 0.95 p<0.001 -0.6 ASTEROID rosuvastatin -1.2 50 60 70 80 90 100 110 120 Mean low-density lipoprotein cholesterol (mg/dL)