Lipid management in ACS: Should we go lower faster?

Low-density lipoprotein-cholesterol (LDL-C) is a well-accepted causal risk factor for athero-thrombotic cardiovascular disease, as demonstrated in large epidemiological studies, including Mendelian randomization data. Several randomized controlled trials and meta-analyzes have shown that lipid lowering therapies, such as statins and more recently the non-statin agents ezetimibe and Proprotein Convertase Subtilisin Kexin type 9 (PCSK9) monoclonal antibodies (mAb), reduce cardiovascular events across a broad range of baseline LDL-C levels. Over time, the recommended target for LDL-C has become more stringent, moving from 2.6 mmol/l to 1.8 mmol/l in very high-risk patients. It is currently recommended to start high intensity statin treatment immediately after acute coronary syndromes (ACS) to maximally and rapidly reduce LDL-C. The novel treatment options enable the achievement of very low LDL-C levels below 1 mmol/l, with no reported safety issues, in particular with regard to neurocognitive events. However, current evidence supports the use of PCSK9 mAb treatment in ACS patients only after an initial 2-3 month run-up treatment adaptation period with maximally tolerated statin. The use of PCSK9 mAb immediately in the acute phase of ACS (<1 month) remains to be studied. Some data suggest that circulating PCSK9 increases coronary plaque vulnerability, inflammation as well as platelet aggregation in the acute phase of ACS, potentially justifying earlier PSCK9 mAb treatment initiation. As the use of novel treatment combinations in ACS is further explored to widen the perspectives of a more personalized approach for the management of ACS based on individual patient risk profile and baseline LDL-C values, their relative cost-effectiveness will also need to be assessed.