Low-Density Lipoprotein Cholesterol Lowering With Inclisiran Plus Usual Care in Recent Acute Coronary Syndrome:...

Managing low-density lipoprotein cholesterol (LDL-C) in patients with recent acute coronary syndrome remains a clinical challenge. Established guidelines recommend LDL-C reduction to mitigate cardiovascular risk, but the effectiveness of newer agents in this population is unclear. Prior research has shown that statins remain the cornerstone of treatment, but gaps persist in achieving target LDL-C levels. Some patients experience statin intolerance, limiting treatment options. This uncertainty drove the need for alternative therapies. Inclisiran, a small interfering RNA targeting proprotein convertase subtilisin/kexin type 9, has shown promise in other populations. However, no prior work had resolved its efficacy in recent acute coronary syndrome. The lack of data on inclisiran in this specific group motivated the current trial. This gap motivated the design of a trial that mimics real-world clinical settings. The study aimed to address this unmet need in a high-risk patient population.

The goal of the VICTORION-INCEPTION trial was to evaluate whether inclisiran could lower LDL-C in patients with recent acute coronary syndrome. These patients are at high risk for further cardiovascular events. The study focused on individuals who had been discharged within five weeks of screening and had LDL-C levels above 70 mg/dL. Participants were either on statin therapy or statin intolerant. The researchers aimed to determine if inclisiran plus usual care could achieve guideline-directed LDL-C goals. The trial was designed to reflect real-world clinical practice. The primary endpoints were LDL-C goal attainment and percentage change from baseline at Day 330. The study also aimed to assess the safety profile of inclisiran in this population. This trial was the first to test inclisiran in recent acute coronary syndrome patients.

The VICTORION-INCEPTION trial was a phase 3b, open-label, multicenter study. It enrolled 400 participants who had been discharged after acute coronary syndrome within five weeks of screening. Eligible patients had LDL-C levels of at least 70 mg/dL or non-high-density lipoprotein cholesterol of at least 100 mg/dL. Participants were randomized in a 1:1 ratio to receive either inclisiran sodium 300 mg (284 mg inclisiran equivalent) on Days 0, 90, and 270 plus usual care or usual care alone. Usual care involved clinician-directed LDL-C management. The trial was open-label, meaning both participants and clinicians knew the treatment assignments. The study followed participants for 330 days to assess outcomes. The primary endpoints were LDL-C goal attainment and percentage change from baseline at Day 330. Adverse events were monitored throughout the study period.

At Day 90, the inclisiran plus usual care group showed significantly greater LDL-C goal attainment compared to the usual care group. Specifically, 74.6% of participants in the inclisiran group achieved LDL-C <70 mg/dL, compared to 26.6% in the usual care group. The odds ratio was 10.84 (97.5% CI, 6.13-19.16). For the more stringent LDL-C <55 mg/dL goal, 63.2% of the inclisiran group achieved it, compared to 8.5% in the usual care group, with an odds ratio of 26.58 (95% CI, 14.14-49.98). The percentage change from baseline was -48.9% in the inclisiran group versus 2.2% in the usual care group. These results were sustained at Day 330, with 66.7% of the inclisiran group achieving LDL-C <70 mg/dL versus 28.1% in the usual care group (OR, 5.42; 97.5% CI, 3.29-8.91). For LDL-C <55 mg/dL, 54.2% of the inclisiran group achieved it versus 13.6% in the usual care group (OR, 8.24; 95% CI, 4.97-13.65). The percentage change from baseline remained -46.9% in the inclisiran group. Adverse events were comparable between the two groups, with 58.6% in the inclisiran group and 53.3% in the usual care group.

The VICTORION-INCEPTION trial demonstrated that inclisiran plus usual care led to rapid and sustained attainment of LDL-C goals in patients with recent acute coronary syndrome. The results suggest that early initiation of inclisiran can significantly improve LDL-C levels compared to usual care alone. The study found that the LDL-C <70 mg/dL goal was achieved by 66.7% of the inclisiran group at Day 330, compared to 28.1% in the usual care group. The more stringent LDL-C <55 mg/dL goal was achieved by 54.2% of the inclisiran group versus 13.6% in the usual care group. The percentage change from baseline remained significant at -46.9% in the inclisiran group. The safety profile of inclisiran was comparable to usual care, with no significant differences in adverse events. The researchers propose that inclisiran may be a valuable addition to usual care for managing LDL-C in this high-risk population. The trial supports the potential role of inclisiran in achieving guideline-directed LDL-C goals in recent acute coronary syndrome patients.