Lipid-lowering therapy in acute coronary syndrome: Limitations of the stepwise approach and rationale for a ‘strike early, strike strong’ strategy

Acute coronary syndrome (ACS) is associated with a markedly increased risk of recurrent cardiovascular events, particularly during the early post-event period, which is characterized by persistent inflammation, endothelial dysfunction, plaque vulnerability, and ongoing thrombotic activation. Extensive evidence has demonstrated a strong relationship between cumulative exposure to low-density lipoprotein cholesterol (LDL-C) and the development and progression of atherosclerosis, while randomized clinical trials have consistently shown that LDL-C reduction is associated with proportional reductions in cardiovascular risk. In addition, current guidelines recommend intensive LDL-C targets in patients with recent ACS. Despite the availability of highly effective lipid-lowering therapies, a substantial proportion of patients fail to achieve recommended LDL-C goals in routine clinical practice. This gap may be partially explained by the limitations of the traditional stepwise ("step-up") treatment strategy, in which lipid-lowering therapy is progressively intensified during outpatient follow-up. Each step of this process represents a potential point of failure involving patient-, physician-, and healthcare system-related factors, potentially delaying optimal lipid control during the period of greatest vulnerability. In response to these challenges, an alternative "strike early, strike strong" approach has emerged, advocating for earlier and more intensive lipid-lowering therapy during the index hospitalization. This review critically examines whether the traditional stepwise strategy remains adequate in ACS management or whether current evidence supports a paradigm shift toward early combination lipid-lowering therapy.