Use of combination therapy is associated with improved LDL cholesterol management: 1-year follow-up results from the European observational SANTORINI study

Eur J Prev Cardiol. 2024 Nov 11;31(15):1792-1803. doi: 10.1093/eurjpc/zwae199.

Abstract

Aims: To assess whether implementation of the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) dyslipidaemia guidelines observed between 2020 and 2021 improved between 2021 and 2022 in the SANTORINI study.

Methods and results: Patients with high or very high cardiovascular (CV) risk were recruited across 14 European countries from March 2020 to February 2021, with 1-year prospective follow-up until May 2022. Lipid-lowering therapy (LLT) and 2019 ESC/EAS risk-based low-density lipoprotein (LDL) cholesterol (LDL-C) goal attainment (defined as <1.4 mmol/L for patients at very high CV risk and <1.8 mmol/L for patients at high CV risk) at 1-year follow-up were compared with baseline. Of 9559 patients enrolled, 9136 (2626 high risk and 6504 very high risk) had any available follow-up data, and 7210 (2033 high risk and 5173 very high risk) had baseline and follow-up LDL-C data. Lipid-lowering therapy was escalated in one-third of patients and unchanged in two-thirds. Monotherapy and combination therapy usage rose from 53.6 and 25.6% to 57.1 and 37.9%, respectively. Mean LDL-C levels decreased from 2.4 to 2.0 mmol/L. Goal attainment improved from 21.2 to 30.9%, largely driven by LLT use among those not on LLT at baseline. Goal attainment was greater with combination therapy compared with monotherapy at follow-up (39.4 vs. 25.5%).

Conclusion: Lipid-lowering therapy use and achievement of risk-based lipid goals increased over 1-year follow-up particularly when combination LLT was used. Nonetheless, most patients remained above goal; hence, strategies are needed to improve the implementation of combination LLT.

Keywords: Cardiovascular risk; Dyslipidaemia; Europe; Lipid; Real-world clinical trials.

Plain language summary

Cardiovascular (CV) diseases, a group of disorders of the heart and blood vessels, are the most common cause of death worldwide. Lowering LDL cholesterol (LDL-C) in the bloodstream reduces the risk of the development of CV diseases such as heart attacks and strokes. Guidelines recommend that those at the highest risk of CV disease should achieve the lowest levels of LDL-C. Several medications are available that help lower LDL-C levels and prevent CV events; however, recent studies have shown that the majority of patients continue to have LDL-C levels above optimal value in part due to a suboptimal use of these medications. In this study, we report the results after 1 year of follow-up of the SANTORINI study (started in 2020), which aimed to document the management of LDL-C in clinical practice across 14 countries in Europe. We found that a better control of LDL-C occurred when more than one drug was used (combination therapy). The use of combination therapy was low at the start of the study (25.6%) but increased over 1 year to 37.9%, resulting in a better control of LDL-C at 1 year than observed at the start of the study. Nonetheless, only 31% of patients achieved their LDL-C target levels based on the European guidelines. A greater use of combination therapies is needed in order to improve the overall population-level control of LDL-C.

Publication types

  • Observational Study
  • Multicenter Study

MeSH terms

  • Aged
  • Anticholesteremic Agents / therapeutic use
  • Biomarkers / blood
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / prevention & control
  • Cholesterol, LDL* / blood
  • Drug Therapy, Combination*
  • Dyslipidemias* / blood
  • Dyslipidemias* / diagnosis
  • Dyslipidemias* / drug therapy
  • Dyslipidemias* / epidemiology
  • Europe
  • Female
  • Follow-Up Studies
  • Guideline Adherence
  • Heart Disease Risk Factors
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hypolipidemic Agents / therapeutic use
  • Male
  • Middle Aged
  • Practice Guidelines as Topic
  • Prospective Studies
  • Risk Assessment
  • Time Factors
  • Treatment Outcome

Substances

  • Cholesterol, LDL
  • Biomarkers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypolipidemic Agents
  • Anticholesteremic Agents

Grants and funding