Early Triple Lipid-Lowering Therapy in Acute Coronary Syndrome: Results from the multicentric LAI-REACT Study

Background/Synopsis

Patients experiencing acute coronary syndrome (ACS) are at high risk for recurrent cardiovascular events, necessitating a rapid reduction in low-density lipoprotein cholesterol (LDL-C). High-intensity statins (HIS) alone often fail to achieve guideline-recommended target levels. While proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) can improve outcomes, their high-cost limits accessibility, particularly in resource-constrained settings like India. Early initiation of triple combination therapy—HIS, ezetimibe, and bempedoic acid (BA)—may enhance lipid-lowering efficacy.

Objective/Purpose

The multicentric LAI-REACT (Lipid Association of India Recommended Early and Aggressive Lipid Lowering in ACS with Triple Combination Therapy) study aimed to evaluate the LDL-C-lowering efficacy of a novel regimen consisting of rosuvastatin 40 mg, ezetimibe 10 mg, and BA 180 mg daily (REB regimen) in statin-naïve patients diagnosed with ACS.

Methods

This prospective, multicentre investigation enrolled 516 statin-naïve ACS patients across five centres in India. All participants commenced treatment with the triple combination REB therapy upon admission. Lipid profiles were assessed at baseline and at weeks 1, 2, 4, and 6.

Results

The mean age of participants was 57.8 ± 11.2 years. The mean LDL-C concentration at admission was 116.9 ± 36.1 mg/dL, decreasing to 47.6 ± 17.9 mg/dL at week 1, and further to 44.1 ± 17.9 mg/dL at week 2. Levels stabilized at 44.1 ± 16.8 mg/dL at week 4 and reached 47.1 ± 19.4 mg/dL by week 6. Percentage reductions in LDL-C were significant across all time points: 59.3%, 62.3%, 61.6%, and 59.7% at weeks 1, 2, 4, and 6, respectively (p<0.001). Non-HDL cholesterol levels exhibited significant reductions of 52.9% at week 1, 55.3% at week 2, 54.4% at week 4, and 52.6% at week 6 (p<0.001). Mean apo-B levels decreased from 92.1 ± 24.1 mg/dL at admission to 62.6 ± 21.4 mg/dL by week 4, a 29.5% reduction. Target LDL-C levels <70 mg/dL were achieved in 89.8%, 91.5%, 92.2%, and 88.3% of patients at weeks 1, 2, 4, and 6, respectively. Similarly, target LDL-C levels <50 mg/dL were achieved in 61.3%, 72.9%, 69.2%, and 65.1% of patients at weeks 1, 2, 4, and 6, respectively.

Conclusions

The multicentric LAI-REACT study demonstrates that triple REB therapy rapidly and effectively achieves LDL-C targets following ACS, with significant reductions observed as early as one week and maintained through six weeks of follow-up. This regimen offers a cost-effective alternative to PCSK9 inhibitors, potentially improving long-term cardiovascular outcomes for high-risk populations in India.