Abstract Body (Do not enter title and authors here): Background: Patients with acute coronary syndrome (ACS) face a high risk of recurrent events in the early post ACS period. Rapid reduction of low-density lipoprotein cholesterol (LDL-C) is crucial, but high-intensity statins (HIS) alone often fall short of goals.

Research Hypothesis: Early use of triple combination therapy of HIS with non-statin drugs: ezetimibe and bempedoic acid (BA) is likely to help achieving the target goals rapidly.

Aim: The LAI-REACT (Lipid Association of India Recommended Early and aggressive lipid lowering in ACS with triple Combination Therapy) study evaluated the LDL-C lowering efficacy of a novel triple combination REB (40 mg rosuvastatin, 10 mg ezetimibe, and 180 mg bempedoic acid daily), in patients with ACS.

Methods: The multicentric LAI-REACT study enrolled 369 statin-naïve ACS patients across five Indian centers. All received the triple REB combination upon admission. Lipid profiles were assessed at baseline and weeks 1, 2, 4, and 6.

Results: The mean age of the study population was 56.3 ± 11.3 years. The mean LDL-C at admission was 119.2 ± 37.1 mg/dL, which significantly decreased to 49.4 ± 19.3 mg/dL at week 1, 44.7 ± 17.4 mg/dL at week 2, 44.6 ± 16.6 mg/dL at week 4, and 46.7 ± 18.3 mg/dL at week 6. The percentage reductions in LDL-C at weeks 1, 2, 4, and 6 were 58.6%, 62.5%, 62.6%, and 60.8% respectively (repeated measures ANOVA, p<0.001). Similarly, non-HDL cholesterol levels demonstrated significant reductions of 53.1%, 54.7%, 54.6%, and 54.9% at weeks 1, 2, 4, and 6 respectively (repeated measures ANOVA, p<0.001). Mean apo-B levels decreased from 92.3 ± 23.6 mg/dL at admission to 65.2 ± 24.1 mg/dL at week 4 (29.4% reduction). Target LDL-C < 70 mg/dL was achieved in 87.3%, 92.1%, 93.2%, and 90.5% of patients at weeks 1,2,4 and 6 weeks respectively. Similarly, target LDL-C < 50 mg/dL was achieved in 55.2%, 70.6%, 69.6% and 64.6% of patients at 1,2,4 and 6 weeks respectively.

Conclusion: The LAI-REACT study demonstrates the rapid and sustained efficacy of triple REB therapy in achieving LDL-C goals after ACS. Significant reductions in LDL-C were observed as early as the first week and were maintained up to the sixth week of follow-up. This affordable regimen provides an alternative to more expensive inhibitors of proprotein convertase subtilisin/kexin type 9, potentially improving access to effective lipid-lowering therapy in India.