STATINE E RISCHIO CARDIOVASCOLARE RESIDUO

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1 STATINE E RISCHIO CARDIOVASCOLARE RESIDUO Paolo Rubba, [email protected] Medicina Interna e Vascolare, Policlinico, Universita di Napoli Federico II 18 1-year CV risk Prevalence of CV events % 45 CV events % 15% 1% 5% % of events 75% of events % of total events in 1 years I (3433) II (1659) III (8) IV (439) V (253) VI (161) VII (115) VIII (79) IX (62) X (55) 1-year CV risk decile (exposed population)

2 STATINE E RISCHIO CARDIOVASCOLARE RESIDUO # Statine: effetti su lipidi e lipoproteine # Effetti vascolari anti-aterosclerotici # Prevenzione degli eventi cardiovascolari Statine: percentuale di pazienti a target di LDL-C secondo Linee Guida a 52 settimane Raggiunto a 1mg Raggiunto a 2mg Raggiunto a 4mg Raggiunto a 8mg Insuccessi Pazienti a target C-LDL (%) % 2.8 (n=14) +5.2% +5.2% +18.1% +58.6% 13.4 (n=134) +2.4% +11.3% +82.1% Dose media (mg) 96.2% Atorvastatina Rosuvastatina Olsson AG, Am Heart J 22; 144:

3 Change in LDL-C in atherosclerotic disease subgroup Results from the VOYAGER individual patient data meta-analysis Dose, mg (log scale) 5mg 1mg 2mg 4 mg 8mg Change in LDL-C from baseline (%) (n=3) -35 (n=3595) -38 (n=224) -41^ -44 * (n=5183) -33 (n=1564) (n=2174) -5 (n=186) -39 (n=287) -46^ (n=85) -55 (n=227) Simvastatin Atorvastatin Rosuvastatin -46^ (n=112) -5 # (n=1482) *p<.1 rosuvastatin 1mg vs atorvastatin 1mg & 2mg; simvastatin 1mg, 2mg & 4mg; p<.1 rosuvastatin 2mg vs atorvastatin 2mg & 4mg; simvastatin 2mg & 4mg; p<.1 rosuvastatin 4mg vs atorvastatin 4mg & 8mg; simvastatin 4mg & 8mg; ^p<.5 vs rosuvastatin 5mg; # p<.5 atorvastatin 8mg vs rosuvastatin 5mg & 1mg Nicholls S et al. Atherosclerosis Supplements 29; 1 (2); Abs P964 Change in LDL-C in atherosclerotic disease subgroup Results from the VOYAGER individual patient data meta-analysis Rosuvastatin Atorvastatin Simvastatin Dose (mg) n=224 n=5183 n=186 n=227 n=3595 n=2174 n=85 n=1482 n=3 n=1564 n=287 n=112 LS mean (SE) % change from baseline * ^ ^ # ^ -6 *p<.1 rosuvastatin 1mg vs atorvastatin 1mg & 2mg; simvastatin 1mg, 2mg & 4mg; p<.1 rosuvastatin 2mg vs atorvastatin 2mg & 4mg; simvastatin 2mg & 4mg; p<.1 rosuvastatin 4mg vs atorvastatin 4mg & 8mg; simvastatin 4mg & 8mg; ^p<.5 vs rosuvastatin 5mg; # p<.5 atorvastatin 8mg vs rosuvastatin 5mg & 1mg Nicholls S et al Atherosclerosis Supplements 29; 1 (2); Abs P964

4 Change in HDL-C in atherosclerotic disease subgroup Results from the VOYAGER individual patient data meta-analysis LS mean (SE) % change from baseline * n=224 n=5183 n=186 n=227 n=3595 n=2174 n=85 n=1482 n=3 n=1564 n=287 n= Rosuvastatin Atorvastatin Simvastatin Dose, mg (log scale) *p<.5 rosuvastatin 1mg vs atorvastatin 1mg, 2mg, 4mg & 8mg; p<.1 rosuvastatin 2mg vs atorvastatin 2mg, 4mg & 8mg and p=.2 vs simvastatin 2mg; p<.1 rosuvastatin 4mg vs atorvastatin 4mg & 8mg and p=.6 vs simvastatin 4mg; Nicholls S et al. Atherosclerosis Supplements 29; 1 (2); Abs P964 RISPOSTA TERAPEUTICA ATTESA PER DIVERSI LIVELLI DI PARTENZA DI COLESTEROLO LDL CON DIVERSE STATINE A DIVERSI DOSAGGI ( Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischemic heart disease, and stroke: systematic review and meta-analysis. BMJ 23; 326:1423-6) LIVELLI DI PARTENZA DI COLESTEROLO LDL 16 mg/dl 18 mg/dl 2 mg/dl STATINE Dopo Atorva 1 mg : 11 mg/dl 113 mg/dl 126 mg/dl Dopo Atorva 2 mg : 91 mg/dl 13 mg/dl 114 mg/dl Dopo Atorva 4 mg : 82 mg/dl 92 mg/dl 12 mg/dl Dopo Rosuva 1 mg : 91 mg/dl 13 mg/dl 114 mg/dl Dopo Rosuva 2 mg : 83 mg/dl 94 mg/dl 14 mg/dl Dopo Fluva 8 mg : 17 mg/dl 121 mg/dl 134 mg/dl Dopo Simva 2 mg : 19 mg/dl 122 mg/dl 136 mg/dl Dopo Simva 4 mg : 11 mg/dl 113 mg/dl 126 mg/dl Dopo Prava 4 mg : 114 mg/dl 128 mg/dl 142 mg/dl In giallo evidenziato il mancato raggiungimento del target terapeutico di 1 mg/dl

5 ALGORITMO TERAPIA DELLE DISLIPIDEMIE CON STATINE Rosuvastatina 1-2 mg/die Paziente di nuova diagnosi, Intervento su stile vita LDL colesterolo > 16 mg/dl Atorvastatina 2-4 mg/die ammesso a rimborsabilita (dieta, abolizione fumo, (Nota 13, AIFA 27) attivita fisica) LDL colesterolo < 16 mg/dl Farmaco equivalente Paziente gia in terapia, Intervento su stile vita LDL colesterolo > 1 mg/dl Aumento dose o farmaco piu efficace ammesso a rimborsabilita (dieta, abolizione fumo, (Nota 13, AIFA 27) attivita fisica) LDL colesterolo < 1 mg/dl Mantiene terapia in corso Circolare interpretativa, Assessorato Sanita, Settore Farmaceutico, Giunta Regionale Campania, STATINE E RISCHIO CARDIOVASCOLARE RESIDUO # Statine: effetti su lipidi e lipoproteine # Effetti vascolari anti-aterosclerotici # Prevenzione degli eventi cardiovascolari

6 METEOR primary endpoint: Rate of change of maximum IMT at 12 carotid sites Rosuvastatin vs placebo Change in maximum IMT of 12 carotid sites (mm) mm/yr (n=252) 1 Rosuvastatin 4 mg -.14 mm/yr (n=624) P<.1 (Rosuva vs. placebo) 2 P=NS (Rosuva vs. zero slope Time (years) ; Change in CIMT (95% CI) Progression Regression Rosuvastatin 4 mg; Change in CIMT (95% CI) Crouse JR, et al. JAMA : Regression of Atherosclerosis in a Patient in the Trial Nissen, S. E. et al. JAMA 26;: jpc62-1. Copyright restrictions may apply.

7 Variazioni della %DS in funzione delle variazioni del C-LDL negli Studi sulla QCA Statin* MARS CCAIT PLAC I LCAS LCAS MAAS CCAIT PLAC I MARS MAAS On-Treatment LDL-C (mg/dl) ASTEROID Progression Regression * ASTEROID - rosuvastatin; MAAS - simvastatin; CCAIT - lovastatin; MARS lovastatin; LCAS - fluvastatin; PLAC I - pravastatin Ref: Ballantyne C et al. Circulation 28 DOI: /CIRCULATIONAHA Please consult local Prescribing Information for guidance on the use of CRESTOR Variazioni della %DS in funzione delle variazioni del C-HDL negli Studi sulla QCA Change in % Stenosis per year PLAC I MAAS CCAIT CCAIT PLAC I MARS MAAS LCAS MARS LCAS Statin* On-Treatment HDL-C (mg/dl) ASTEROID Progression Regression * ASTEROID - rosuvastatin; MAAS - simvastatin; CCAIT - lovastatin; MARS lovastatin; LCAS - fluvastatin; PLAC I - pravastatin Ref: Ballantyne C et al. Circulation 28 DOI: /CIRCULATIONAHA Please consult local Prescribing Information for guidance on the use of CRESTOR

8 Studio Yun et al. Rosuva 4 vs prima della PCI, FU 3d (R1 a tutti) End-point Primario: incidenza di IMA peri-procedurale procedurale STATINE E RISCHIO CARDIOVASCOLARE RESIDUO # Statine: effetti su lipidi e lipoproteine # Effetti vascolari anti-aterosclerotici # Prevenzione degli eventi cardiovascolari

9 Effetti preventivi / tollerabilita nella terapia ad alte dosi con Atorvastatina Atorva 1mg Atorva 8 Significativita (p) (n 56) (n 4995) Eventi cardiovascolari totali Eventi cardiovascolari maggiori (end-point) Scompenso cardiaco Ictus Interruzione (per eventi avversi) Mialgia n.s Iper-transaminasemia (Studio TNT, Treating to New Targets. La Rosa JC et al, N Engl J Med 25; 352: ) JUPITER study design No history of CAD men 5 yrs women 6 yrs LDL-C <13 mg/dl CRP 2. mg/l run-in Rosuvastatin 2 mg (n=891) (n=891) Visit: Week: monthly Final Lead-in/ eligibility Randomisation Lipids CRP Tolerability Lipids CRP Tolerability Median follow-up 1.9 years Lipids CRP Tolerability HbA 1C CAD=coronary artery disease; LDL-C=low-density lipoprotein cholesterol; CRP=C-reactive protein; HbA 1c =glycated haemoglobin Ridker P et al. N Eng J Med 28;359:

10 Distribuzione dei fattori di rischio nella popolazione JUPITER % Età > 65 anni 52 % Fumatori 15,8 % Storia familiare di CHD 11,5 % Ipertensione (controllata) 57,3 % BMI % Sindrome metabolica 41,4 % Framingham risk 1% 5 % Fattori di rischio ATP-III 2* 64 % * Inclusa l età Ridker P et al. N Eng J Med 28;359: JUPITER - Laboratory Safety Data Rosuvastatin p-value [n=891] [n=891] Laboratory Values, N (%) Serum creatinine 1 (.1) 16 (.2).24 ALT > 3 x ULN # 17 (.2) 23 (.3).34 Glycosuria 32 (.4) 36 (.5).64 Laboratory Values, median values (IQR) GFR *, (ml/min/1.73m 2 ) 66.6 ( ) 66.8 ( ).2 % HbA1c ** 5.8 ( ) 5.9 ( ).1 Fasting plasma glucose **, (mg/dl) 98 (9-16) 98 (91-17).12 GFR = Glomerular filtration rate, HbA1c = Haemoglobin A1c # on consecutive visits, >1% increase from baseline, *at 12 months, **at 24 months, >trace at 12 months Ridker P et al. N Eng J Med 28;359:

11 JUPITER Effects on LDL-C, HDL-C, TG and hscrp at 12 months; Percentage change between rosuvastatin and placebo 1 LDL-C HDL-C TG hscrp Percentage change from baseline (%) % p<.1 4% p<.1* 17% p<.1 37% p<.1 Ridker P et al. N Eng J Med 28;359: JUPITER - Primary Endpoint Time to first occurrence of a CV death, non-fatal stroke, non-fatal MI, unstable angina or arterial revascularization Cumulative Incidence Number at Risk Rosuvastatin Hazard Ratio.56 (95% CI ) P< Follow-up (years) Rosuvastatin 2 mg 8,91 8,631 8,412 6,54 3,893 1,958 1, ,91 8,621 8,353 6,58 3,872 1,963 1, % NNT for 2y = 95 5y* = 25 Ridker P et al. N Eng J Med 28;359:

12 JUPITER - Total Mortality Death from any cause Cumulative Incidence Number at Risk Rosuvastatin Hazard Ratio.8 (95% CI ) p= Follow-up (years) 8,91 8,847 8,787 6,999 4,312 2,268 1,62 1, ,91 8,852 8,775 6,987 4,319 2,295 1,614 1, Rosuvastatin 2mg -2% Ridker P et al. N Eng J Med 28;359: Incidenza di eventi in funzione dei livelli di C-LDL raggiunti nei trial con le Statine 4S - Incidenza di eventi (%) (1.) Rx - Statin therapy PRA pravastatin ATV - atorvastatin Prevenzione Secondaria 4S - Rx LIPID - LIPID - Rx CARE - CARE - Rx HPS - Rx TNT ATV1 HPS - Prevenzione Primaria TNT ATV8 PROVE-IT - PRA WOSCOPS AFCAPS - JUPITER - Rx 6 (1.6) 8 (2.1) AFCAPS - Rx WOSCOPS - Rx ASCOT - ASCOT - Rx JUPITER - 1 (2.6) 12 (3.1) 14 (3.6) 16 (4.1) LDL-C, livelli raggiunti, mg/dl (mmol/l) 6 18 (4.7) 2 (5.2)

13 Chi e come trattare con statine? Novita attese nelle prossime Linee Guida Trattare tutti i pazienti a rischio cardiovascolare elevato e intermedio Terapia ipo-colesterolemizzante efficace e sicura per ridurre gli eventi cardiovascolari Trattare in modo continuativo con statine / dosaggi che permettano di raggiungere gli obiettivi terapeutici (7mg/dL)