Effects of a stepwise, structured LDL-C lowering strategy in patients post-acute coronary syndrome

Objective: Low-density lipoprotein cholesterol (LDL-C) lowering constitutes a cornerstone of secondary prevention of atherosclerotic cardiovascular disease (ASCVD), yet a considerable number of patients do not achieve guideline-recommended LDL‑C targets. The 2016 European guidelines recommended titration of LDL‑C lowering medication in a set number of steps, starting with oral medication. We aimed to investigate the effects of this stepwise approach in post-acute coronary syndrome (ACS) patients. Methods: In a multicentre, prospective, non-randomised trial, we evaluated a three-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 4–6 weeks, included: 1) start high-intensity statin (HIST); 2) addition of ezetimibe; 3) addition of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i). The primary outcome was the proportion of patients achieving LDL-C ≤ 1.8 mmol/l after Steps 1 and 2 (using oral medications alone). Secondary outcomes examined the prevalence of meeting the target throughout all steps (https://onderzoekmetmensen.nl/nl/trial/21157). Results: 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 23 patients at each respective step. Conclusion: 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).