71 CONGRESSO NAZIONALE FIMMG METIS Domus de Maria, 9 ottobre 2015
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1 71 CONGRESSO NAZIONALE FIMMG METIS Domus de Maria, 9 ottobre 2015 L OTTIMIZZAZIONE DELLA TERAPIA IPOLIPEMIZZANTE NEL PAZIENTE POST-SCA ALLA LUCE DELLE REECENTI EVIDENZE I DATI DELLE REALTA ITALIANA E LE NUOVE PROSPETTIVE ALLA LUCE DELLE RECENTI EVIDENZE Pasquale Perrone Filardi Università Federico II Napoli
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3 Contribution of Changes in Population Growth, Population Aging, and Rates of Age- Specific Cardiovascular Death to Changes in Cardiovascular Mortality, N Engl J Med Apr 2;372(14):
4 The PROSPECT Trial 700 pts with ACS UA (with ECGΔ) or NSTEMI or STEMI >24º undergoing PCI of 1 or 2 major coronary arteries at up to 40 sites in the U.S. and Europe Metabolic S. Waist circum Fast lipids Fast glu HgbA1C Fast insulin Creatinine PCI of culprit lesion(s) Successful and uncomplicated Formally enrolled PI: Gregg W. Stone Sponsor: Abbott Vascular; Partner: Volcano Biomarkers Hs CRP IL-6 scd40l MPO TNFα MMP9 Lp-PLA2 others
5 PROSPECT: MACE All Culprit lesion (CL) related Non culprit lesion (NCL) related Indeterminate 20.4% MACE (%) % 11.6% % Time in Years Number at risk ALL CL related NCL related Indeterminate
6 PROSPECT: VH-TCFA and Non Culprit Lesion Related Events Lesion HR 3.84 (2.22, 6.65) 6.41 (3.35, 12.24) (5.53, 21.00) (4.30, 27.22) P value < < < < Prevalence* 51.2% 17.4% 11.0% 4.6% *Likelihood of one or more such lesions being present per patient. PB = plaque burden at the MLA
7 Up to a third of patients who are event free for the first year post-mi, will suffer a MI, stroke or death within 3 years APOLLO 4-country analysis : Observed Incidence *US sample restricted to patients aged 65 years. MI, myocardial infarction. Rapsomaniki E, et al. ESC Late Breaking Registry presentation 2014: In press. 7
8 PURE Study Drug use in participants with coronary heart disease or stroke, by country economic status and overall Yusuf et al. Lancet 2011
9 SECONDARY PREVENTION IN ITALY Perrone Filardi et al. Nutr, Met and Cardiovasc Dis 2012 NORD 20 centri 288 paz. CENTRO 7 centri 192 paz. SUD 15 centri 286 paz. SICILIA 5 centri 58 paz. SARDEGNA 2 centri 89 paz. TOTALE 49 centri 913 paz. 76 paz. 123 paz. 57 paz. 32 paz. 4 paz. 61 paz. 19 paz. 108 paz. EUROASPIRE III 300 pazienti Periodo di osservazione: 30 Nov Feb paz. 257 paz. 7 paz. 22 paz. 58 paz.
10 SECONDARY PREVENTION IN ITALY % OF PATIENTS WITH PREVIOUS CARDIOVASCULAR EVENTS AND LDL-C > 70 mg/dl Perrone Filardi et al. Nutr, Met and Cardiovasc Dis 2012 n=878 % of patients % diabetics (91% on statins) 83% Non-diabetics
11 On line, december 1, 2014
12 Urbinati et al for the BLITZ 4 Inv. Eur J Prev Cardiol on line, december 1, 2014
13 Adherence to guidelines after 6 months Urbinati et al for the BLITZ 4 Inv. Eur J Prev Cardiol on line, december 1, 2014
14 High- Moderate- and Low-Intensity Statin Therapy (Used in RCTs reviewed by the Expert Panel) Circulation Nov;12
15 Use of intensive lipid-lowering therapy in patients with ACS in the Get With The Guidelines Program 138,216 patients discharged, 119,387 (86.4%) receiving LLT and 14,279 (10.3%) without LLT; LLT contraindicated in 4,550 (3.3%). Intensive LLT defined as therapy likely to achieve a 50% reduction in LDL-C - atorvastatin mg, rosuvastatin mg, simvastatin 80 mg, any statin + ezetimibe Am Heart J 2011;161:
16 Switching from intensive to moderate statin therapy after an acute coronary event 1,321 patients discharged on atorvastatin 80mg/day* 486 (37%) continued atorvastatin 80mg/day 278 (21%) discontinued therapy Median time to discontinuation 37 days (IQR days) 557 (42%) switched to moderate statin therapy Median time to switching 28 days (IQR days) 102 (18%) switched to a lower dose of atorvastatin 327 (59%) switched to simvastatin 57 (16%) switched to pravastatin 41 (7%) switched to fluvastatin Mean dose 24mg/day Mean dose 27mg/day Mean dose 40mg/day Mean dose 80mg/day *1321 consecutive patients (886 men, mean age 71.1 ± 8.7 years) discharged on atorvastatin 80mg/day after an ACS in a 6.5-year period Colivicchi F, et al. Int J Cardiol (2011), 152: 56-60
17 La sostituzione dell atorvastatina 80 mg con una terapia ipolipemizzante meno efficace si associa ad un significativo peggioramento della prognosi clinica Incremento di circa 3 volte della probabilità di eventi cardiovascolari sfavorevoli. In caso di interruzione precoce (entro 30 giorni dalla dimissione) la probabilità di eventi sfavorevoli aumenta fino ad oltre 5 volte. Colivicchi F, et al. Int J Cardiol (2011); 152: 56-60
18 Cause riferite di interruzione della terapia con statine dopo un evento coronarico acuto Troppe pillole No clear medical reason Side effects 52% 48% 0% 20% 40% 60% 80% 100% Effetti collaterali riferiti Dispepsia Astenia Cefalea Mialgie Aumento asintomatico delle transaminasi Aumento asintomatico del CK totale Colivicchi F, et al. Eur Heart J 2008;29 (Suppl. 1):68
19 Comparison of the Effects of Maximal Dose Atorvastatin and Rosuvastatin Therapy on Cholesterol Synthesis and Absorption Markers : a post-analysis of STELLAR Trial Wide individual response to therapy for LDL-C LDL cholesterol change (%) Rosuvastatin Atorvastatin 40 mg 80 mg Mean % LDL-C - 55% - 53% van Himbergen et al J Lipid Res 2009
20 LDL-c ed incremento delle CK CK >10 ULN, % Atorvastatina (10, 20, 40, 80 mg) Cerivastatian (0.2, 0.3, 0.4, 0.8 mg) Pravastatina (20, 40 mg) Rosuvastatina (10, 20, 40 mg) Simvastatina (40, 80 mg) % Riduzione C-LDL Brewer HB Jr. Am J Cardiol 2003; 92:23K-29K
21 Very Low Levels of Atherogenic Lipoproteins and the Risk for Cardiovascular Events : A Meta-Analysis of Statin Trials A total of 38,153 study participants Distribution of achieved on-statin LDL-C levels and the risk of major CV events 40% LDL-C >70 mg/dl Histograms displaying the distribution of achieved LDL-C in patients treated with high-dose statins JACC 2014 Aug 5;64:
22 IMPLICATIONS FROM IMPROVE IT TRIAL PATHOPHYSIOLOGICAL IMPROVE IT RESULTS POINT TO EVEN MORE INTENSIVE LDL REDUCTION FOR TREATMENT OF RESIDUAL RISK IN SECONDARY PREVENTION GUIDELINES MORE STRINGENT IMPLEMENTATION OF ESC GUIDELINES LDL TARGET IN SECONDARY PREVENTION EZITIMIBE IS FIRST NON STATIN DRUG DEMONSTRATING CLINICAL BENEFIT IN RCT UPGRADE CLASS OF RECOMMENDATION IN GUIDELINES EVIDENCE FOR NEW LDL TARGET? CLINICAL PRACTICE COMBINATION THERAPY AS FIRST CHOICE OPTION IN PATIENTS REQUIRING >50% REDUCTION OF LDL (EVEN IF AND ABLE TO ASSUME HIGH POTENCY STATINS) FIRST CHOICE OPTION IN STATIN INTOLERANT PATIENTS
23 Recommendations for long-term management after non-st-elevation acute coronary syndromes Eur Heart J Aug 29. pii: ehv320
24 Studio EZ-PATH Confronto tra raddoppio di atorvastatina e aggiunta di ezetimibe nel raggiungere l obiettivo di C-LDL<70 mg/dl Pazienti in goal a C-LDL opzionale alla settimana 6 (%) Atorvastatina 80 mg c (n=279) 74 b Ezetimibe 10 mg + atorvastatina 40 mg d (n=277) a <70 mg/dl (<1,8 mmol/l); b p <0,001 vs atorvastatina 80 mg; c C-LDL basale = 90 mg/dl; e C-LDL basale = 89 mg/dl Leiter et al. Am J Cardiol 2008;102:
25 The Role of PCSK9 in the Regulation of LDL Receptor Expression
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28 PERSPECTIVES EFFICACY AND SAFETY OF VERY LOW LDL VALUES CLINICAL VALUE OF NON LDL TREATMENTS HDL (NO MENDELIAN RANDOMIZATION CONFIRMATION) TG (MENDELIAN RANDOMIZATION CONFIRMATION) MIXED DYSLIPIDEMIA LIP a APOC3 CLINICAL VALUE OF NON LDL TARGETS NON HDL CHOLESTEROL TG, HDL, LIP a
The PROSPECT Trial. A Natural History Study of Atherosclerosis Using Multimodality Intracoronary Imaging to Prospectively Identify Vulnerable Plaque
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