Triple Versus Dual Lipid-Lowering Therapy in Acute Coronary Syndrome: The ES-BempedACS Randomized Clinical Trial.

BACKGROUND

Current guidelines recommend a stepwise strategy to achieve low-density lipoprotein cholesterol (LDL-C) goals after acute coronary syndrome (ACS). Earlier intensive strategies based on a combination of lipid-lowering therapies (LLTs) could be useful from the onset of ACS. However, the role of bempedoic acid in ACS, particularly when combined with high-intensity statins and ezetimibe, remains uncertain. The aim of ES-BempedACS (Efficacy and Security of Bempedoic Acid in Acute Coronary Syndrome) was to compare the efficacy and safety of triple LLT (high-dose, high-intensity statin+ezetimibe+bempedoic acid) versus standard of care (high-dose, high-intensity statin+ezetimibe) after ACS.

METHODS

ES-BempedACS is a multicenter, independent, pragmatic, prospective, randomized, open, blinded end point controlled trial conducted in 12 Spanish hospitals between November 2023 and October 2024. The primary end point was the proportion of patients achieving LDL-C <55 mg/dL (<1.4 mmol/L) at 8 weeks after ACS, comparing triple LLT with standard of care.

RESULTS

A total of 206 patients (59.5±10.9 years of age [mean±SD]; 21.4% women) were randomized within the first 72 hours of ACS to triple LLT or standard therapy of high-intensity statin+ezetimibe (ie, dual LLT). The baseline LDL-C level was 133.6±28.8 mg/dL. After 8 weeks, the LDL-C level was reduced to <55 mg/dL in 59.4% of patients in the triple LLT group compared with 53.1% in the control group (dual LLT; P=0.376). The percentage change in LDL-C level was 57.5±17.8% and 56.9±18.5% in the triple and dual LLT groups, respectively (P=0.823). Triple versus dual LLT showed similar results in reduction of non-high-density lipoprotein cholesterol levels (49.0±25.4 in triple LLT versus 49.1±31.2 in dual LLT; P=0.970) and triglyceride levels (14.9±36.9 in triple LLT versus 16.8±36.0 in dual LLT;) P=0.718), without differences in adverse events.

CONCLUSIONS

Both dual and triple LLT after ACS allow for high rates (>50%) of adequate LDL-C control (<55 mg/dL) at 8 weeks. Adding bempedoic acid to statin-ezetimibe therapy in the setting of ACS is safe but failed to improve the percentage of patients achieving the LDL-C goal (<55 mg/dL) at 8 weeks. Larger, randomized studies are needed to confirm our findings.

REGISTRATION: URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2021-006550-31.