QUELLE ORDONNANCE APRS L'ANGIOPLASTIE ? AU-DEL DES STATINES - PowerPoint PPT Presentation

QUELLE ORDONNANCE APRÈS L'ANGIOPLASTIE ? AU-DELÀ DES STATINES … Etienne PUYMIRAT Département de Cardiologie Hôpital Européen Georges Pompidou Université Paris Descartes, Paris, France Fees for lectures and/or consulting: Amgen, Astra-Zeneca, Bayer, Biotronik, BMS, Boehringer Ingelheim, Daiichi-Sankyo, Lilly, MSD, The Medicine Company, Sanofi, Saint Jude Medical, Servier, Siemens

Role du LDL-C dans l‘athérogénèse

Recommandations ESC/EAS

� Forte doses de statines � Introduction des statines entre J1 et J4 � Objectif LDL-C < 1.8mM (< 0.70 mg/dl) � Réévaluation du bilan lipidique entre 4 à 6 mois 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. EHJ 2016

Bénéfices CV et limites de statines % reduction of events CTT collaborators Lancet 2005

Prescriptions de statines après un IdM STEMI NSTEMI AMI LDL, mg/dl 1.23 ± 0.42 1.15 ± 0.45 1.19 ± 0.43 Statines : - Before 22% 35% 28% - < 48 h 91% 85% 88.5% - At discharge 94% 89% 92% Atorvastatine 63% 55.5% 59.5% 80mg 43% 30% 38% <50% Rosuvastatine 26% 24% 25% 20mg 9.5% 7% 8.5% Données personnelles

Prise en charge de la dyslipidémie

Association statine & ezetimibe HDL-C TG LDL-C 5 3 ** ** 1 0 -5 -3 -4 -10 % Variation -15 -14 -11 % -20 -25 -21% *** *** -25 -30 Statine et PBO, N=388 * * Statine et EZE, N=375 Gagne et al. AJC 2002 *p<0.001 vs statin + placebo; **p<0.05 vs statin + placebo; *** p< 0.01 vs statin + placebo

Study Design Study Design Patients stabilized post ACS ≤ 10 days: *3.2mM LDL-C 50–125*mg/dL (or 50–100**mg/dL if prior lipid-lowering Rx) **2.6mM N=18,144 Standard Medical & Interventional Therapy Simvastatin Ezetimibe / Simvastatin Uptitrated to Simva 80 mg 40 mg 10 / 40 mg if LDL-C > 79 Follow-up Visit Day 30, every 4 90% power to detect months ~9% difference Duration: Minimum 2 ½-year follow-up (at least 5250 events) Primary Endpoint: CV death, MI, hospital admission for UA, coronary revascularization ( ≥ 30 days after randomization), or stroke Cannon CP AHJ 2008;156:826-32; Califf RM NEJM 2009;361:712-7; Blazing MA AHJ 2014;168:205-12

LDL- -C and Lipid Changes C and Lipid Changes LDL 1 Yr Mean LDL-C TC TG HDL hsCRP Simva 69.9 145.1 137.1 48.1 3.8 EZ/Simva 53.2 125.8 120.4 48.7 3.3 Δ in mg/dL -16.7 -19.3 -16.7 +0.6 -0.5 Baisse de 26% Median Time avg 69.5 vs. 53.7 mg/dL Baisse de 43%

Primary Endpoint — — ITT ITT Primary Endpoint Cardiovascular death, MI, documented unstable angina requiring rehospitalization, coronary revascularization ( ≥ 30 days), or stroke HR 0.936 CI (0.887, 0.988) Simva — 34.7% p=0.016 2742 events NNT= 50 EZ/Simva — 32.7% 2572 events 7-year event rates

Safety — — ITT ITT Safety No statistically significant differences in cancer or No statistically significant differences in cancer or muscle- - or gallbladder or gallbladder- -related events related events muscle Simva EZ/Simv n=9077 a % n=9067 p % ALT and/or AST ≥ 3x ULN 2.3 2.5 0.43 Cholecystectomy 1.5 1.5 0.96 Gallbladder-related AEs 3.5 3.1 0.10 Rhabdomyolysis* 0.2 0.1 0.37 Myopathy* 0.1 0.2 0.32 Rhabdo, myopathy, myalgia with CK elevation* 0.6 0.6 0.64 Cancer* (7-yr KM %) 10.2 10.2 0.57 * Adjudicated by Clinical Events Committee % = n/N for the trial duration

Total Primary Endpoint Events Total Primary Endpoint Events 4983 4983 4562 Total Events 4562 -421 RR 0.91 P=0.007 -251 Additional Events # Events # Events RR 0.88 (0.79-0.98) 1st Event -170 HR 0.936 P=0.016 Simvastatin Ezetimibe Alone Simvastatin

Prise en charge de la dyslipidémie

FOURIER ODYSSEY OUTCOMES 27,564 patients 18,924 patients Placebo vs Evolocumab (140mg/15J ou 420 mg/mois) Placebo vs Alirocumab (75mg/15J ajusté sur LDL-C) Age moyen 62,5 ans (25% de femmes) Age moyen 58,5 ans (25% de femmes) Suivi moyen 2,2 ans Suivi moyen 2,8 ans Sabatine MS et al. NEJM 2017 Schwartz GG et al. NEJM 2018

FOURIER ODYSSEY OUTCOMES 27,564 patients 18,924 patients Placebo vs Evolocumab (140mg/15J ou 420 mg/mois) Placebo vs Alirocumab (75mg/15J ajusté sur LDL-C) Age moyen 62,5 ans (25% de femmes) Age moyen 58,5 ans (25% de femmes) Suivi moyen 2,2 ans Suivi moyen 2,8 ans Sabatine MS et al. NEJM 2017 Schwartz GG et al. NEJM 2018

FOURIER ODYSSEY OUTCOMES 27,564 patients 18,924 patients Placebo vs Evolocumab (140mg/15J ou 420 mg/mois) Placebo vs Alirocumab (75mg/15J ajusté sur LDL-C) Age moyen 62,5 ans (25% de femmes) Age moyen 58,5 ans (25% de femmes) Suivi moyen 2,2 ans Suivi moyen 2,8 ans ≥ 40 ans • 40-85 ans • • Athérosclérose documentée : • Post Syndrome Coronarien Aigu (1-12 � ATCD IDM mois) � ATCD AVC ischémique LDL-C ≥ 70mg/L � Artériopathie périphérique symptomatique • LDL-C ≥ 70mg/L • Sabatine MS et al. NEJM 2017 Schwartz GG et al. NEJM 2018

Recommandations ESC/EAS Global high-risk markers on coronary CTA : � Left main disease � Prox LAD disease � 3 Vessel disease Focal high-risk markers on coronary CTA : � Sténosis severity >50% � Lesion composition : mixed or non-calcified 2017 Update of ESC/EAS Task Force on practical clinical guidance for PCSK9 inhibitors. EHJ 2017

CONCLUSION • Dyslipidémie : Quelle ordonnance après l’angioplastie coronaire ? Objectifs : LDL-C Risque <0.7g/L CV