Terapia Ipolipemizzante

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1 Terapia Ipolipemizzante Alfonso Bellia UNIVERSITA DI ROMA TOR VERGATA Dipartimento di Medicina dei Sistemi POLICLINICO TOR VERGATA UOC di Endocrinologia e Diabetologia

2 Alfonso Bellia dichiara di non avere conflitti di interesse riguardo i contenuti di questa lettura Albano Laziale, 9/6/2018

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4 T2DM: Unique lipid profile atherogenic diabetic dyslipidemia with Insulin resistance playing a Key Role MAIN FEATURES Quantitative Variable increase in LDL, HDL-C, Triglycerides (TGs), VLDL, Chylomicron Postprandial TRL Catabolism: LDL, VLDL, chylomicron, HDL Qualitative changes Small, dense LDL and HDL particles, larger VLDL1 particles Kinetic changes Production: Chylomicron, VLDL Catabolism: LDL, Chylomicron, VLDL, HDL Non-HDL-C: stronger predictor of CVD than LDL-C DM (accounts for all atherogenic lipoproteins) Watts G. Diapedia Available at: Last accessed September 2016; Verges B. Diabetologia 2015;58:886 9

5 Le Statine a TUTTI i Diabetici? Standard italiani per la cura del diabete mellito 2018 «Il colesterolo LDL è l obiettivo primario della terapia» «La terapia con statine è la terapia di prima scelta per i soggetti con diabete con livelli di colesterolo LDL non a target con il solo intervento non farmacologico» Livello della prova I; Forza della raccomandazione A

6 CARDS: The Collaborative Atorvastatin Diabetes Study Purpose: To assess the effectiveness of 10 mg atorvastatin daily in the primary prevention of cardiovascular disease in patients with T2D but without high concentrations of LDL-cholesterol (<160 mg/dl)

7 Diabetes Risk: statins vs placebo OR 1.09 (95% IC ) Increased risk in older people and those with dysglycemia at baseline Increased risk with high-dose/potency statins, independently of LDL-C goal Diabetes risk CV events reduction NNH = 1/255 Adapted from Sattar, N et al. Lancet 2010; 375:735-42; Preiss, D et al. JAMA. 2011;305: NNT = 5.4/255 (per -1 mmol/mol LDL)

8 Prevalence (95%CI) of adherence to CV medications among partecipants in prospective studies: a systematic review and meta-analisys Eur Heart J. 2013;34(38):

9 Terapia Ipolipemizzante nel Diabete: Quali i Target? Standard italiani per la cura del diabete mellito 2018 «Nei soggetti con diabete in prevenzione cardiovascolare primaria e senza addizionali fattori di rischio, il target raccomandato è LDL<100 mg/dl; nei soggetti con malattia cardiovascolare e/o multipli fattori di rischio (evidenza di danno d organo) il target raccomandato è LDL<70 mg/dl» Livello della prova I; Forza della raccomandazione A

10 Patients with high CV risk face challenges in achieving LDL-C goals (US data) Jones PH, et al. J Am Heart Assoc. 2012;1:e doi: /JAHA Statins are the standard of care for HC management However, many patients are not reaching their recommended LDL-C goal with statin therapy LDL-C Goal <100 mg/dl High risk patients LDL-C Goal <70 mg/dl 23% not at goal 76% not at goal

11 The SHARP (Study of Heart and Renal Protection) trial 4650 adult patients with CKD (23% with T2D) Primary outcome of major atherosclerotic events (coronary death, MI, nonhemorrhagic stroke, or any revascularization) In T2D subgroup: RR 0.78; 95%CI Baigent C et al. Lancet. 2011;377:

12 Benefit of Adding Ezetimibe to Statin Therapy on Cardiovascular Outcomes and Safety in Patients With Versus Without Diabetes Mellitus (IMPROVE.IT Trial) T2D in 4933 (27%) of randomized pts Giugliano RP et al. Circulation. 2018;137:

13 Role of PCSK9 in the Regulation of LDL Receptor Expression 1 3 Adapted from Catapano & Papadopoulos Atherosclerosis 2013;228:

14 Impact of a PCSK9 Monoclonal Antibody on LDL Receptor Expression 1 4 Adapted from Catapano & Papadopoulos Atherosclerosis 2013;228:

15 Regulatory Status EMA MAA : 23 September 2015 MAA : 17 July 2015 Adults with primary hypercholesterolaemia includes HeFH and non-familial He Mixed dyslipidaemia Low-fat diet + statin ± other fat-lowering medicines, in patients who do not adequately respond to the maximum tolerated dose of the statin Alone or in combination ± other fat-lowering medicines in patients who cannot tolerate or cannot be given statins.

16 CV Outcomes Trials with PCSK-9 Inhibitors

17 The FOURIER Study: Diabetes Subgroup LDL-C Reduction Other Lipid Parameters Sabatine MS et al. Lancet Diabetes Endocrinol. 2017;5:

18 The FOURIER Study: Diabetes Subgroup Primary Endpoint Key Secondary Endpoints Sabatine MS et al. Lancet Diabetes Endocrinol. 2017;5:

19 The ODISSEY OUTCOMES Trial with Alirocumab Pts Disposition Baseline Demographics

20 The ODISSEY OUTCOMES Trial with Alirocumab LDL-C Reduction Primary Endopint: MACE

21 Take home message: L obiettivo lipidico (riduzione LDL-C) è prioritario nella cura del T2D Attenzione all inerzia terapeutica! Molti farmaci con documentata efficacia: usarli con giudizio per raggiungere gli obiettivi terapeutici e ottimizzare l aderenza

22 These analyses illustrate the so-called nocebo effect, with an excess rate of musclerelated AE reports only when patients and their doctors were aware that statin therapy was being used and not when its use was blinded. These results should help counter the adverse effect on public health of exaggerated claims about statin-related side-effects. Lancet. 2017;389: