2024 Recommendations on the Optimal Use of Lipid-Lowering Therapy in Established Atherosclerotic Cardiovascular Disease and Following Acute Coronary Syndromes: A Position Paper of the International Lipid Expert Panel (ILEP)

Abstract

Atherosclerotic cardiovascular disease (ASCVD) and consequent acute coronary syndromes (ACS) are substantial contributors to morbidity and mortality across Europe. Fortunately, as much as two thirds of this disease's burden is modifiable, in particular by lipid-lowering therapy (LLT). Current guidelines are based on the sound premise that, with respect to low-density lipoprotein cholesterol (LDL-C), "lower is better for longer", and recent data have strongly emphasised the need for also "the earlier the better". In addition to statins, which have been available for several decades, ezetimibe, bempedoic acid (also as fixed dose combinations), and modulators of proprotein convertase subtilisin/kexin type 9 (PCSK9 inhibitors and inclisiran) are additionally very effective approaches to LLT, especially for those at very high and extremely high cardiovascular risk. In real life, however, clinical practice goals are still not met in a substantial proportion of patients (even in 70%). However, with the options we have available, we should render lipid disorders a rare disease. In April 2021, the International Lipid Expert Panel (ILEP) published its first position paper on the optimal use of LLT in post-ACS patients, which complemented the existing guidelines on the management of lipids in patients following ACS, which defined a group of "extremely high-risk" individuals and outlined scenarios where upfront combination therapy should be considered to improve access and adherence to LLT and, consequently, the therapy's effectiveness. These updated recommendations build on the previous work, considering developments in the evidential underpinning of combination LLT, ongoing education on the role of lipid disorder therapy, and changes in the availability of lipid-lowering drugs. Our aim is to provide a guide to address this unmet clinical need, to provide clear practical advice, whilst acknowledging the need for patient-centred care, and accounting for often large differences in the availability of LLTs between countries.

Fig. 1

The summary of the different activities that might effectively improve statin adherence and avoid discontinuation. Based on the Eur Heart J Open. 2022 Oct 26;2(6):oeac071 [16] with permission (licence number: 5820250572831). EAS European Atherosclerosis Society, IlEP International Lipid Expert Panel, LDL-C low-density lipoprotein cholesterol, NLA National Lipid Association, SI statin intolerance

Fig. 2

Overall pathway of optimal LLT in ASCVD patients. The pathway is divided into three stages: (1) diagnosis and stratification; (2) target-driven lipid-lowering therapy; (3) support and follow-up. Special pathways are provided for specific treatment groups, including those with extreme CV risk (as defined in this document), familial hypercholesterolaemia, statin intolerance, and diabetes/metabolic disorders. At each step of LLT, adherence should be carefully monitored. ACS acute coronary syndrome, ASCVD atherosclerotic cardiovascular disease, CV cardiovascular, FDC fixed dose combination, HeFH heterozygous familial hypercholesterolaemia, HIS high intensity statin, LDL-C low-density lipoprotein cholesterol, LLT lipid-lowering therapy, PCSK9I proprotein convertase subtilisin/kexin type 9 inhibitor

Fig. 3

Special pathway for patients with extreme CV risk. At each step of LLT, adherence should be carefully monitored. CV cardiovascular, FDC fixed dose combination, HIS high-intensity statin, LDL-C low-density lipoprotein cholesterol, LLT lipid-lowering therapy, PCSK9I proprotein convertase subtilisin/kexin type 9 inhibitor

Fig. 4

Special pathway for participants with objectively confirmed partial/complete statin intolerance. At each step of LLT, adherence should be carefully monitored. FDC fixed dose combination, LDL-C low-density lipoprotein cholesterol, LLT lipid-lowering therapy, PCSK9I proprotein convertase subtilisin/kexin type 9 inhibitor

Fig. 5

Special pathway for participants with ASCVD and metabolic disorders. At each step of LLT, adherence should be carefully monitored. ASCVD atherosclerotic cardiovascular disease, FDC fixed dose combination, HIS high-intensity statin, LDL-C low-density lipoprotein cholesterol, LLT lipid-lowering therapy, PCSK9I proprotein convertase subtilisin/kexin type 9 inhibitor

Fig. 6

Key reasons for non-adherence based on the PoLA Lipid Guidelines 2021 [44] with permission. PoLA Polish Lipid Association