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

Area of Science:

• Cardiology
• Pharmacology
• Preventive Medicine

Background:

• Low-density lipoprotein cholesterol (LDL-C) lowering is crucial for secondary prevention of atherosclerotic cardiovascular disease (ASCVD).
• Many patients with atherosclerotic cardiovascular disease (ASCVD) do not reach guideline-recommended LDL-C targets.
• The 2016 European guidelines suggest a stepwise medication titration approach.

Purpose of the Study:

• To evaluate the effectiveness of a stepwise lipid-lowering therapy strategy in post-acute coronary syndrome (ACS) patients.
• To assess the proportion of patients achieving LDL-C ≤ 1.8 mmol/l using oral medications alone.
• To determine the overall success rate of LDL-C target achievement with escalating therapy.

Main Methods:

• A prospective, multicentre, non-randomised trial involving 999 post-ACS patients with prior ASCVD and/or diabetes mellitus.
• A three-step strategy was implemented: 1) high-intensity statin (HIST), 2) addition of ezetimibe, 3) addition of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i).
• LDL-C levels were assessed every 4-6 weeks, with the primary outcome being LDL-C ≤ 1.8 mmol/l after steps 1 and 2.

Main Results:

• 84% of patients achieved the LDL-C target of ≤ 1.8 mmol/l using only high-intensity statins and/or ezetimibe.
• In an intention-to-treat analysis, 69% achieved the target after step 1, 84% after step 2, and 87% after step 3.
• Protocol deviations occurred in 23, 38, and 23 patients at each respective step.

Conclusions:

• Stepwise intensification of lipid-lowering therapy effectively achieved LDL-C targets in a high percentage of very high-risk post-ACS patients.
• 84% of patients reached the LDL-C goal of ≤ 1.8 mmol/l using oral medications (statin and/or ezetimibe).
• The addition of PCSK9 inhibitors further increased the achievement rate to 87%.