LDL-c levels and clinical outcomes in acute myocardial infarction patients with prior ischemic stroke

Abstract

The optimal low-density lipoprotein cholesterol (LDL-c) target after acute myocardial infarction (AMI) in patients with prior ischemic stroke remains uncertain, particularly regarding the trade-off between ischemic protection and bleeding risk. We evaluated the association between LDL-c levels achieved at three month and clinical outcomes at one year in this high-risk population. In this multicenter, real-world cohort study, consecutive AMI patients with a history of ischemic stroke were enrolled from 82 hospitals between 2010 and 2024. Among 5,682 patients who survived to the 3-month lipid reassessment and under statin therapy, achieved LDL-c levels were categorized as <1.4, 1.4–1.8, 1.8–2.6, 2.6–3.4, and ≥3.4 mmol/L (reference group, Figure 1). Multivariable Cox proportional hazards models adjusting for demographic, clinical, and treatment characteristics were used to estimate 1-year risks. Compared with LDL-c ≥3.4 mmol/L, achieving LDL-c levels between 1.4 and 2.6 mmol/L was associated with significantly lower all-cause mortality (aHR: 0.57–0.69, all p < 0.05). LDL-c 2.6–3.4 mmol/L also conferred a survival benefit (aHR: 0.62, 95% CI: 0.43–0.89; p = 0.009). In contrast, LDL-c <1.4 mmol/L was not associated with additional mortality reduction (aHR: 0.91, 95% CI: 0.62–1.31; p = 0.599). No significant differences were observed in cardiac mortality or recurrent myocardial infarction across LDL-c strata. Importantly, LDL-c <1.4 mmol/L was independently associated with increased major bleeding risk (aHR: 1.79, 95% CI: 1.24–2.58; p = 0.002) (Figure 2A). Net clinical benefit analysis demonstrated a non-linear, inverted U-shaped relationship, with the greatest net benefit observed at LDL-c 1.8–2.6 mmol/L (Figure 2B). In AMI patients with prior ischemic stroke, achieving very low LDL-c (<1.4 mmol/L) was not associated with incremental survival benefit but was linked to increased bleeding risk. Moderate LDL-c levels (1.8–2.6 mmol/L) were associated with the most favorable overall risk profile. These findings challenge the “lower-is-always-better” paradigm and support individualized lipid-lowering strategies in patients with concomitant cerebrovascular disease.Baseline Characteristics TableClinical outcomes and Net clinical benefit