Addition of bempedoic acid versus statin titration in high-risk patients not reaching LDL-c target

In a single-center RCT among patients with high CVD risk and LDL-c >70 mg/dL, addition of bempedoic acid to their statin and ezetimibe combination therapy was more effective in reducing LDL-c levels at 12 weeks than doubling the statin dose.

This summary is based on the publication of Marazzi G, Caminiti G, Perrone MA, et al. - Addition of Bempedoic Acid to Statin–Ezetimibe versus Statin Titration in Patients with High Cardiovascular Risk: A Single-Centre Prospective Study. J Cardiovasc Dev Dis. 2024 Sep 14;11(9):286. doi: 10.3390/jcdd11090286

Introduction and methods

Background

Although combining statins with ezetimibe can potentiate the LDL-c-lowering effects of statins [1-3], many patients at high CVD risk who receive this combination therapy are unable to reach LDL-c targets [4]. Bempedoic acid, alone or in addition to statins plus ezetimibe, has been shown to effectively reduce LDL-c levels [5-7]. It also reduced the incidence of MACE in statin-intolerant patients [8]. However, the exact role of bempedoic acid in the prevention of ASCVD has not yet been established.

Aim of the study

The authors compared the effects of bempedoic acid as add-on therapy versus titration of the statin dose on reducing LDL-c levels in patients with high CVD risk who were on background therapy with high-intensity statins and ezetimibe and had not achieved the LDL-c goal.

Methods

In an open-label, parallel-group RCT, 120 adults at high CVD risk (based on SCORE2) who had a previous diagnosis of hypercholesterolemia and current LDL-c >70 mg/dL despite combination therapy with high-intensity statins plus ezetimibe for ≥3 months were enrolled at the San Raffaele IRCCS cardiology outpatient service in Rome, Italy. Participants were randomized to bempedoic acid 180 mg daily or statin titration (i.e., doubling of statin dose); both groups continued their statin and ezetimibe combination therapy.

Outcomes

The primary endpoint was the change in LDL-c level from baseline to 12 weeks. The secondary endpoint was the number of patients reaching the LDL-c target (<70 mg/dL) at 12 weeks.

Main results

• At 12 weeks, the median (± SD) decrease in LDL-c level from baseline was larger in patients receiving bempedoic acid (n=60) than those assigned to statin titration (n=60) (−20.5 ± 7.3 vs. −6.7 ± 2.5 mg/dL; between-group difference: −13.8 mg/dL; 95%CI: −11.6 to –15.3; P=0.002). This corresponded with a 22.9% and 7.5% LDL-c reduction, respectively.
• In the bempedoic acid group, the LDL-c reduction at 12 weeks was similar in patients taking atorvastatin/ezetimibe and those on rosuvastatin/ezetimibe (P=0.253).
• The median total cholesterol level also decreased in the bempedoic acid group compared with the statin titration group (between-group difference: −9.5 mg/dL; 95%CI: −6.7 to –12.3; P=0.013), as did the median non–HDL-c level (between-group difference: –16.8 mg/dL; 95%CI: −13.2 to –19.6; P=0.026).
• There were no significant differences in the change in HDL-c and triglyceride levels between the treatment groups.
• The number of patients who reached LDL-c <70 mg/dL at 12 weeks was 38 (63%) in the bempedoic acid group and 22 (37%) in the statin titration group (P=0.034).
• During the follow up period, no adverse events occurred.

Conclusion

In this single-center, open-label trial among patients at high CVD risk who did not reach the LDL-c target (<70 mg/dL) despite combination therapy with high-intensity statins and ezetimibe, addition of bempedoic acid was more effective in reducing LDL-c levels at 12 weeks than doubling the statin dose. In addition, more patients in the bempedoic acid group achieved the LDL-c goal than those in the statin titration group. “This result suggests that starting bempedoic acid rather than titrating the statin dose would allow a quicker achievement of optimal values of LDL-c,” according to the authors.

Find this article online at J Cardiovasc Dev Dis.

References

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