Post-treatment level of LDL cholesterol and all-cause mortality in patients with atherosclerotic cardiovascular disease: evidence from real-world setting

Aims This study aimed to evaluate the safety of the currently recommended target of LDL cholesterol (LDL-C) control on mortality in patients with atherosclerotic cardiovascular disease (ASCVD).Methods and results Using deidentified electronic health record data, we conducted a multicentre retrospective cohort study involving individuals with documented ASCVD who had received statin treatment for at least 3 months across China. The primary outcomes assessed encompassed all-cause mortality, CV mortality, and non-CV mortality. Relationships between post-treatment LDL-C concentrations and outcomes were evaluated using restricted cubic spline curves based on Cox proportional hazards regression analyses. Additionally, competitive risk models were employed to explore associations between LDL-C levels and cause-specific mortality. Among 33 968 participants, we identified nearly linear associations of post-treatment LDL-C level with all-cause mortality and CV mortality during a median follow-up of 47 months. Notably, patients who achieved the recommended target of LDL-C (<1.4 mmol/L) were at significantly lower risks of all-cause mortality [hazard ratio (HR), 0.77; 95% confidence interval (CI), 0.69-0.86] and CV mortality (subdistribution HR, 0.68; 95% CI, 0.58-0.79), compared with those with LDL-C >= 3.4 mmol/L. This survival benefit was consistent in patients with different intensities of LDL-C reduction and other subgroup analyses. And no correlation was found between post-treatment LDL-C concentration and non-CV mortality.Conclusion Our findings supported the safety of currently recommended target of LDL-C control and the 'lower is better' principle in patients with ASCVD.Lay summary Intensive control of LDL cholesterol (LDL-C) has been widely recommended for cardiovascular (CV) protection in patients with atherosclerotic CV disease. Nevertheless, a U-shaped association between LDL-C levels and all-cause mortality has been noted in several general population studies, prompting concerns regarding the safety of intensive lipid control. In this multicentre cohort comprising 33 968 patients at the highest CV risk, we found that patients with lower post-treatment LDL-C level were at lower risk of both all-cause and CV mortality, and this survival benefit was unaffected by intensity of LDL-C reduction, types of lipid-lowering agents, and other clinical characteristics.