Effects of astepwise, structured LDL-C lowering strategy in patients post-acute coronary syndrome.

Abstract

Low-density lipoprotein cholesterol (LDL-C) lowering constitutes acornerstone of secondary prevention of atherosclerotic cardiovascular disease (ASCVD), yet aconsiderable number of patients do not achieve guideline-recommended LDL‑C targets. The 2016 European guidelines recommended titration of LDL‑C lowering medication in aset number of steps, starting with oral medication. We aimed to investigate the effects of this stepwise approach in post-acute coronary syndrome (ACS) patients. In amulticentre, prospective, non-randomised trial, we evaluated athree-step strategy aiming to reduce LDL‑C to ≤ 1.8 mmol/l in post-ACS patients with prior ASCVD and/or diabetes mellitus. Steps, undertaken every 4-6weeks, included: 1)start high-intensity statin (HIST); 2)addition of ezetimibe; 3)addition of proprotein convertase subtilisin/kexin type9 inhibitors (PCSK9i). The primary outcome was the proportion of patients achieving LDL-C ≤ 1.8 mmol/l after Steps1 and2 (using oral medications alone). Secondary outcomes examined the prevalence of meeting the target throughout all steps ( https://onderzoekmetmensen.nl/nl/trial/21157 ). Out of 999 patients, 84% (95% confidence intervals (CI): 81-86) achieved the LDL‑C target using only statin and/or ezetimibe. In an intention-to-treat analysis, the percentages of patients meeting the LDL‑C target after each step were 69% (95% CI: 67-72), 84% (95% CI: 81-86), and 87% (95% CI: 85-89), respectively. There were protocol deviations for 23,38 and 23patients at each respective step. Through stepwise intensification of lipid-lowering therapy, 84% of very high-risk post-ACS patients achieved an LDL‑C target of ≤ 1.8 mmol/l with oral medications alone. Addition of PCSK9i further increased this rate to 87% (95% CI: 85-89).