Koskinas, KonstantinosKonstantinosKoskinasWindecker, StephanStephanWindeckerPedrazzini, GiovanniGiovanniPedrazziniMueller, ChristianChristianMuellerCook, StéphaneStéphaneCookMatter, Christian MChristian MMatterMuller, OlivierOlivierMullerHäner, JonasJonasHäner0000-0002-1420-8967Gencer, BarisBarisGencerCrljenica, CarmelaCarmelaCrljenicaAmini, PooryaPooryaAminiDeckarm, OlgaOlgaDeckarmIglesias, Juan FJuan FIglesiasRäber, LorenzLorenzRäberHeg, Dierik HansDierik HansHeg0000-0002-8766-7945Mach, FrançoisFrançoisMach2024-10-282024-10-282019-11-19https://boris-portal.unibe.ch/handle/20.500.12422/182051BACKGROUND While guidelines recommend in-hospital initiation of high-intensity statin therapy in patients with acute coronary syndromes (ACS), low-density lipoprotein cholesterol (LDL-C) target levels are frequently not attained. Evolocumab, a rapidly acting, potent LDL-C-lowering drug, has not been studied in the acute phase of ACS. OBJECTIVES To assess the feasibility, safety, and LDL-C lowering efficacy of evolocumab initiated during the in-hospital phase of ACS. METHODS We conducted an investigator-initiated, randomized, double-blind, placebo-controlled trial involving 308 patients hospitalized for ACS with elevated LDL-C levels (≥1.8 mmol/L on high-intensity statin for at least 4 weeks; ≥2.3 mmol/L on low- or moderate-intensity statin; or ≥3.2 mmol/L on no stable dose of statin). Patients were randomly assigned 1:1 to receive subcutaneous evolocumab 420mg or matching placebo, administered in-hospital and after 4 weeks, on top of atorvastatin 40mg. The primary endpoint was percentage change in calculated LDL-C from baseline to 8 weeks. RESULTS Most patients (78.2%) had not been on previous statin treatment. Mean LDL-C levels decreased from 3.61 mmol/L to 0.79 mmol/L at week 8 in the evolocumab group, and from 3.42 mmol/L to 2.06 mmol/L in the placebo group; the difference in mean percentage change from baseline was -40.7% (95% CI: -45.2 to -36.2; p<0.001). LDL-C levels <1.8 mmol/L were achieved at week 8 by 95.7% of patients in the evolocumab group vs. 37.6% in the placebo group. Adverse events and centrally adjudicated cardiovascular events were similar in both groups. CONCLUSIONS In this first randomized trial assessing a PCSK9 antibody in the very high-risk setting of ACS, evolocumab added to high-intensity statin therapy was well tolerated and resulted in substantial reduction in LDL-C levels, rendering >95% of patients within currently recommended target levels.enEvolocumab LDL-C PCSK9 inhibitor acute coronary syndrome600 - Technology::610 - Medicine & healtharticle10.7892/boris.1331343147972210.1016/j.jacc.2019.08.010