Almost 1 in 2 Patients with Acute Coronary Syndrome Are Extremely High-Risk and Potential Candidates for In-Hospital Triple Lipid-Lowering Therapy: Data from the CALLINICUS-Hellas Registry

Introduction The great heterogeneity of acute coronary syndrome (ACS) patients in the risk for cardiovascular events recurrence, prompted a recent position paper endorsed by the International Lipid Expert Panel to propose criteria, i.e. coexistence of multivessel coronary artery disease (CAD), polyvascular disease, heterozygous familial hypercholesterolemia (heFH), diabetes mellitus (DM) with estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 and/or lipoprotein (a) [Lp(a)] >50 mg/dL etc., which define the extremely high-risk ACS patients for whom an low-density lipoprotein cholesterol (LDL-C) <40 mg/dL was proposed. Purpose To estimate the proportion of patients with ACS that fulfill the criteria of the extremely high-risk group and are potential candidates for "extremely" intensive early lipid-lowering therapy (LLT) aiming at an LDL-C <40 mg/dL. Methods We recruited 780 consecutive patients with ACS who were participants of the CALLINICUS-Hellas Registry which is a prospective multicenter observational study that explores the adherence to LLT, the achievement of LDL-C targets and the cardiovascular events at 6- and 24-months after hospital discharge of patients with ACS. Results The prevalence of high risk components was: heFH 13.5%, multivessel CAD 44%, polyvascular disease 3.2%,and DM with eGFR <60 ml/min/1.73 m2 and/or Lp(a) >50 mg/dL 8.1%. By excluding the overlapping between these conditions, 430 ACS patients (55.1%) had at least one of the characteristics which define the extremely high-risk patients (Figure). Presuming a 65% LDL-C reduction of the levels (the pretreatment if on LLT prior admission or the admission if not on prior LLT) of the extremely high-risk ACS patients by taking a maximum dual LLT (intense statin plus ezetimibe), 312 patients, i.e., 40% of all initially recruited patients would fail to achieve an LDL-C <40 mg/dL suggesting that they require additional LLT, namely, a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i). Conclusions Almost 1 in 2 patients with ACS have extremely high-risk characteristics and are candidates for in-hospital triple LLT (statin plus ezetimibe plus PCSK9i) aiming at an LDL-C <40 mg/dL, a strategy shown to improve plaque stability and possibly to reduce the recurrence rate of early coronary events.Figure