Impact of a personalized, fire-to-target lipid-lowering strategy in patients with acute coronary syndrome
J Herrera, J Lopez Aguilera, J Castillo, C Herrera, R Gonzalez, S Ojeda, M AnguitaAbstract
Introduction
Acute coronary syndrome (ACS) is associated with a persistently high risk of recurrent ischemic events, particularly during the first year after discharge. The 2025 ESC Focused Update on Dyslipidaemias and the 2023 ESC Guidelines for ACS endorse a “strike early, strike strong” approach (STS), emphasizing rapid treatment intensification to achieve LDL-C <55 mg/dL and/or ≥50% reduction from baseline in very-high-risk patients. However, real-world data assessing the clinical impact of a structured “fire-to-target” strategy (using the full range of modern lipid-lowering agents) remain limited.
Purpose
To evaluate whether a structured “fire-to-target” strategy, consistent with the “STS” paradigm, improves achievement of the LDL-C <55 mg/dL target and reduces 12-month major adverse cardiovascular events compared with prior standard-of-care management.
Methods
We performed a retrospective cohort study including consecutive patients discharged alive after ACS (STEMI, NSTEMI, or unstable angina) between January 2022 and December 2023. Patients discharged in 2022 received a traditional stepwise lipid-lowering approach, whereas the 2023 group was managed with an early, proactive fire-to-target strategy based on upfront combination lipid-lowering therapy, including high dose statins, ezetimibe, bempedoic acid, PCSK9 inhibitors and inclisiran. Primary endpoints were achievement of LDL-C <55 mg/dL at follow-up (at 1, 6, and 12 months after discharge) and a composite of all-cause death, myocardial infarction, or stroke (3P-MACE) at 12 months.To minimize confounding, analyses were conducted using inverse probability of treatment weighting (IPTW)-adjusted regression models accounting for clinical characteristics and cardiovascular risk factors.
Results
A total of 710 eligible patients (mean age, 66.0 ± 11.6 years; 51.4% men) were included (353 managed with a stepwise approach and 357 with the fire-to-target strategy). Baseline characteristics were broadly comparable between groups. During follow-up, treatment intensification was more frequent in the fire-to-target group, with greater use of non-statin lipid-lowering therapies. LDL-C levels were significantly lower in the intervention group at 1, 6, and 12 months, translating into a higher proportion of patients achieving the LDL-C target throughout follow-up. The multivariable analysis before IPTW, showed that all-cause mortality (1.7% vs 7.1%; HR, 0.23; 95% CI, 0.10–0.57; p=0.001) and the 3P-MACE (5.9% vs 11%; HR, 0.51; 95% CI, 0.30–0.87; p=0.012) at 12 months were significantly lower in the fire-to-target group. After IPTW, the difference in all-cause death (aHR, 0.30; 95% CI, 0.10–0.87; p=0.026) and 3P-MACE (aHR, 0.49; 95% CI, 0.26–0.91; p=0.023) between groups remained significant at 1 year.
Conclusion
In routine clinical practice, a personalized,“fire-to-target” lipid strategy improves LDL-C target achievement and significantly reduces short-term cardiovascular events.