I benefici dell associazione Ezetimibe e statina nei pazienti con Cardiopatia Ischemica Cronica. Furio Colivicchi Ospedale S.

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1 I benefici dell associazione Ezetimibe e statina nei pazienti con Cardiopatia Ischemica Cronica Furio Colivicchi Ospedale S.Filippo Neri Roma

2 Approccio Clinico all Ipercolesterolemia. 1 La presenza di elevati valori di Colesterolo LDL si accompagna ad un elevata probabilità di eventi cardiovascolari avversi. Le linee guida internazionali e nazionali sono concordi nel raccomandare la riduzione dei livelli di Colesterolo LDL come intervento terapeutico fondamentale per contrastare il rischio cardiovascolare. Le evidenze scientifiche disponibili indicano che la riduzione del rischio è proporzionale alla diminuzione dei livelli di Colesterolo LDL.

3 Approccio Clinico all Ipercolesterolemia. 2 Al fine di rendere efficace e sicuro l intervento terapeutico ipolipemizzante, il medico deve commisurare il trattamento al reale livello di rischio del singolo paziente. Pertanto, la terapia non deve essere avviata solo sulla base dei valori assoluti della colesterolemia, ma può essere prescritta solo dopo una adeguata valutazione clinico-diagnostica del profilo di rischio cardiovascolare del paziente.

4 Outcomes in primary prevention, stable and unstable coronary disease 16 Death/nonfatal MI (%) Unstable angina/non-q-wave MI (FRISC II) Stable angina (SAPAT) Primary prevention (WOSCOPS) Months of follow-up Wallentin L, et al. Lancet 2000;356:9-16. Juul-Moller S, et al. Lancet 1992;340: Shepherd J, et al. N Engl J Med 1995;333:

5 REACH: 1-year event curves for CV death, MI, stroke & combined endpoints in Stable Atherosclerotic CV Disease Event distribution function (%) n=64,977 Non-fatal stroke CV death Non-fatal MI CV death/mi/stroke 44% of these stable patients had an event within 10 years Time in months Steg PG et al, on behalf of the REACH Registry Investigators. JAMA 2007;297(11):

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7 Relative risk reduction for major coronary events La riduzione del Rischio Relativo risulta indipendente dai livelli iniziali di LDL-C e dalle caratteristiche cliniche del paziente Ogni riduzione di LDL-C di 38 mg/dl si associa ad una riduzione del Rischio Relativo del 24% LDL Cholestrol reduction (mmol/l) Baigent C, et al, Cholesterol Treatment Trialists (CTT) Collaborators. Lancet 2005;366:

8 Proportional major vascular event reductions versus absolute LDL cholesterol reductions in RCTs of routine statin therapy versus no routine statin use and of more intensive versus less intensive regimens Collins R et al. Interpretation of the evidence for the efficacy and safety of statin therapy Lancet 2016; Published Online September 8, 2016

9 Statin therapy is the cornerstone of lipid-lowering treatment There is indisputable evidence that statins reduce the risk of cardiovascular disease, both in patients without or with a previous major cardiovascular event (MI or stroke). There is also evidence that lower LDL cholesterol levels achieved with more intensive statin therapy may result in greater reduction in cardiovascular events. 1. Baigent C, Keecah A, Kearney PM et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005;366: Baigent C, Blackwell L, Emberson J et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010;376:

10 Lipid control for CV Prevention Elevated levels of plasma LDL-C are causal to atherosclerosis. Reduction of LDL-C decreases CV events. Low HDL-C is associated with increased CV risk, but manoeuvres to increase HDL- C have not been associated with a decreased CV risk. Lifestyle and dietary changes are recommended for all. Total CV risk should guide the intensity of the intervention. Total cholesterol and HDL-C are adequately measured on nonfasting samples, thus allowing non-hdl-c to be derived.

11 Recommendations for Lipid Control Most cholesterol is normally carried in LDL-C. There is a strong association between LDL-C and risk of CVD. The evidence that reducing plasma LDL-C reduces CVD risk is unequivocal. Every 1.0 mmol/l reduction in LDL-C (38 mg/dl) is associated with a corresponding 20 25%reduction in CVD mortality and non-fatal MI

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13 A systematic reviewand meta-analysis of the therapeutic equivalence of statins

14 Lipid control for CV Prevention Patients with dyslipidaemia, particularly those with established CVD, DM or asymptomatic high-risk individuals, may not always reach treatment goals, even with the highest tolerated statin dose. Therefore, combination treatment may be needed. It must be stressed, however, that the only combination that has evidence of clinical benefit is that of a statin combined with ezetimibe.

15 IMPROVE IT: Modificazioni del Colesterolo LDL 1 Yr Mean LDL-C TC TG HDL hscrp Simva EZ/Simva in mg/dl Median Time avg 69.5 vs mg/dl

16 IMPROVE IT: Endpoint primario HR CI (0.887, 0.988) p=0.016 Simva 34.7% 2742 events NNT= 50 EZ/Simva 32.7% 2572 events

17 IMPROVE IT: Eventi durante follow up HR Simva* EZ/Simva*p-value All-cause death CVD CHD MI Stroke Ischemic stroke Cor revasc 30d UA CVD/MI/stroke *7-year event rates (%) Ezetimibe/Simva Better Simva Better

18 IMPROVE IT: Analisi dei sottogruppi Simva EZ/Simva Male Female Age < 65 years Age 65 years No diabetes Diabetes * Prior LLT No prior LLT LDL-C > 95 mg/dl LDL-C 95 mg/dl Ezetimibe/Simva Simva Better Better 7-year event rates *p-interaction = 0.023, otherwise > 0.05

19 IMPROVE IT: Primi eventi ed eventi successivi durante il follow up Murphy SA, et al. J Am Coll Cardiol. 2016;67(4):

20 IMPROVE IT: Primi eventi ed eventi successivi durante il follow up in rapporto al trattamento Total Events RR 0.91 P=0.007 Additional Events RR 0.88 ( ) 1st Event HR P=0.016

21 IMPROVE IT: riduzione del numero di eventi Riduzione di eventi per 100 pazienti trattati con associazione ezetimibesimvastatina per 10 anni rispetto al trattamento con sola statina Murphy SA, et al. J Am Coll Cardiol. 2016;67(4):

22 I Valori di C-LDL in corso di terapia ipolipemizzante predicono eventuali successivi eventi post-sca Quanto più basso è il livello di C- LDL in corso di terapia tanto minore sarà il rischio di recidive ischemiche J Am Coll Cardiol. 2016;67(4): doi: /j.jacc

23 General Recommendations for the Pharmacological Management of Hypercholesterolemia 2016 European Guidelines on cardiovascular disease prevention in clinical practice. European Heart Journal (2016) 37, ESC/EAS guidelines for the management of dyslipidaemias. European Heart Journal (2016) doi: /eurheartj/ehw272.