Contemporary LDL-cholesterol management in male and female patients at high-cardiovascular risk: results from the European observational SANTORINI study

Abstract Background Middle aged women have a faster increase in atherosclerotic cardiovascular disease (ASCVD) events than men over time. Undertreatment with guideline-recommended therapy in women may be one of the drivers for this burden. Purpose To compare high- or very high-risk male and female patients regarding contemporary 1-year low-density lipoprotein cholesterol (LDL-C) goal attainment, lipid-lowering therapy (LLT) intensity, and major adverse cardiovascular event (MACE) rate. Methods SANTORINI is an observational, prospective study that enrolled high- and very high-cardiovascular risk patients between March 2020 and Feb 2021, across 623 sites and 14 countries in Europe from primary & secondary care settings, with a further 1-year prospective follow-up. We included all patients with an LDL-C measurement at baseline and 1-year follow up (1yFU) for the current analysis. LDL-C goal attainment was defined separately for high and very-high risk categories according to 2019 ESC/EAS guidelines. Results Overall, 5197 males with a mean age of 65 years, and 2013 females with a mean age 66 years were included. At baseline, male patients had higher prevalence of pre-existing ASCVD (81.6% vs. 63.5%), and a lower prevalence of familial hypercholesterolaemia (8.7% vs. 17.2%) than female patients (Table 1). The proportion of patients reaching LDL-C goal improved from baseline to 1yFU, but was greater in males (22.9% and 33.3%, respectively) than females (16.9% and 24.6%, respectively). Similarly, the proportion of patients receiving no LLT decreased from baseline to 1yFU for both sexes, however, more females than males received no LLT at 1yFU (male: 20.7% to 2.7%; female: 23.9% to 3.9%). High intensity statin use increased for both sexes but was higher for males (22.2% to 27.3%) than for females (15.5% to 19.5%) at 1yFU. By contrast, PCSK9i use at baseline and 1yFU was lower for males (6.6% to 9.3%) than for females (9.8% to 13.4%). Nevertheless, the use of combination LLT at 1yFU was lower among females than males (male: 27.8% to 42.2%; female: 26.7% to 40.2%). During follow-up, MACE-4 was higher in males (5.31/100 patient years [PY]; 95% confidence interval [CI]: 4.68–5.95) than in females (3.63/100PY; 95% CI: 2.79–4.47). Similar results were observed for MACE-3 (Table 2). Conclusions Despite similar guideline recommendations, use of combination LLT and high intensity statin therapy was lower in female patients at high or very high cardiovascular risk than in male patients over one year of follow-up. Accordingly, female patients had lower LDL-C goal attainment both at baseline and at one-year. Nevertheless, due to intrinsic risk factors, female patients had lower rates of MACE-4 and MACE-3 than male patients.