Abstract

Acute Coronary Syndrome (ACS) is associated with a high risk of recurrent cardiovascular events, particularly in the early post-event period, making aggressive lipid-lowering therapy a cornerstone of secondary prevention. Despite the established role of high-intensity statins, many patients fail to achieve recommended Low-Density Lipoprotein Cholesterol (LDL-C) targets, leaving significant residual risk. The aim of this review is to evaluate the mechanistic rationale, clinical evidence, and therapeutic role of PCSK9 inhibitors in Acute Coronary Syndrome (ACS), with a focus on early initiation, plaquestabilizing effects, and their integration into contemporary secondary prevention strategies. Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors, notably Alirocumab and Evolocumab, represent a transformative advance in lipid management. By preventing LDL receptor degradation, they lower LDL-C by 50-60% and lipoprotein(a) by 20-30%, while also exerting anti-inflammatory, antithrombotic, and plaque-stabilizing effects. Clinical trials such as FOURIER and ODYSSEY OUTCOMES have demonstrated significant reductions in major adverse cardiovascular events, with benefits most pronounced in patients with elevated baseline LDL-C. Emerging studies, including EVOPACS, EPIC-STEMI, and PACMAN-AMI, suggest that early or in-hospital initiation of PCSK9 inhibitors accelerates LDL-C reduction, enhances plaque stability, and may improve short-and long-term outcomes. International guidelines now recommend PCSK9 inhibitors for very-high-risk ACS patients, with European societies endorsing rapid escalation and stringent LDL-C targets, while American guidelines adopt a more stepwise approach.

Barriers to wider adoption include cost, access, and physician familiarity. Novel therapies such as Inclisiran, oral PCSK9 inhibitors, vaccines, and gene-editing technologies promise to improve adherence, accessibility, and long-term efficacy. In conclusion, PCSK9 inhibitors provide robust and multifaceted benefits in ACS, offering an effective strategy to reduce residual ischemic risk and reshape the landscape of secondary prevention.