Abstract Body (Do not enter title and authors here): Background: Intensive lipid-lowering therapy can significantly reduce the risk of major adverse cardiovascular events (MACE) in patients with ST-segment elevation myocardial infarction (STEMI). However, post-hoc analysis of the ODYSSEY OUTCOMES study found that Alirocumab did not reduce the risk of MACE in patients with acute coronary syndrome and a history of heart failure (HF).

Research Questions: What is the association between LDL-C levels within 1–3 months after STEMI complicated by HF and major adverse outcomes?

Methods: This cohort study used data from the Tianjin Health and Medical Data Platform in China including patients with STEMI complicated by HF (2013–2022). Those not prescribed statins during hospitalization were excluded. LDL-C levels measured 1–3 months post-STEMI were used as the exposure. The primary outcome was MACE, defined as a composite of all-cause mortality, recurrent myocardial infarction (MI), and stroke, along with each component separately. Restricted cubic splines (RCS) evaluated nonlinear associations between LDL-C and outcomes. Multivariable adjusted Cox models estimated hazard ratio (HR) and 95% confidence interval (CI).

Results: A total of 4,410 patients were included in the study (median follow-up 3 years; mean age 66). Among them, 655 (14.88%) experienced MACE, 311 (7.07%) died, 184 (4.18%) had recurrent MI, and 269 (6.11%) had a stroke. RCS revealed linear positive associations between LDL-C levels and MACE, recurrent MI, and stroke. However, a reverse J-curve emerged for mortality: each 10 mg/dL LDL-C reduction below 70 mg/dL increased death risk by 19% (HR 1.19, 95% CI 1.01-1.40). Threshold analysis (LDL-C <70 vs. >70 mg/dL) showed lower recurrent MI risk (HR 0.59, 95% CI: 0.42-0.84) and borderline MACE reduction (HR 0.85, 95% CI:0.71-1.01), but no mortality benefit (HR 1.00, 95% CI: 0.95-1.30) and stroke benefit (HR: 0.79, 95% CI: 0.60-1.04). Lower LDL-C conferred greater MACE risk reduction in high-risk ischemic subgroups: age >65 years, hypertension, non-percutaneous coronary intervention management, and baseline LDL-C >100 mg/dL at STEMI.

Conclusions: In STEMI patients with HF, achieving LDL-C <70 mg/dL after lipid-lowering therapy was associated with reduced recurrent MI risk but a paradoxical increase in mortality. These findings highlight the need to balance the benefits and risks of intensive lipid-lowering, emphasizing the importance of personalized treatment and further research into its long-term effects.