Bempedoic acid lowers LDL-c safely in subgroups of patients

Safety and efficacy of bempedoic acid in patients with renal impairment

Presented at ACC.22 by Prof. Peter Toth, MD, PhD (Rock Falls, IL, USA)

and

Safety and efficacy of bempedoic acid in patients with hypertension

Presented at ACC.22 by Prof. Keith Ferdinand, MD (New Orleans, LA, USA)

Introduction and methods

There is a need for additional therapies to lower LDL-c, as statins are often underutilized and underdosed. Bempedoic acid is an ATP citrate lyase inhibitor and studies have demonstrated LDL-c lowering with bempedoic acid.

Analyses on the safety and efficacy of bempedoic acid in two subgroups were performed using data of four phase 3 trials; one in patients with elevated LDL-c levels and renal impairment and one in patient with elevated LDL-c levels and hypertension.

In the four phase 3 trials, patients were randomized to bempedoic acid or placebo for 12 to 52 weeks. In 2 studies, patients were on background moderate- to high-intensity statin and in the 2 other studies, patients received low-dose or no statin.

For the analysis of renal function subgroups, 3619 patients were included: 22% had stage 1 (eGFR≥90%), 63% had stage 2 (eGFR 60-89) and 15% stage 3a+b (baseline eGFR 30-59) renal impairment.

For the analysis of hypertension subgroups, 3623 patients were included: 78% had a history of hypertension, which was pharmacologically treated. In addition, in a phase 2 study of 6 weeks with 143 patients, the safety and efficacy of bempedoic acid was assessed in patients with uncontrolled hypertension not receiving statins or other lipid-lowering therapies.

Results

Results in patients with renal impairment

• LDL-c lowering with bempedoic acid compared with placebo was similar in renal function subgroups at week 12 (stage 1:-20.8%; stage 2: -18.8% and stage 3a+b: -21.1%, Pinteraction=0.44).
• ApoB levels were reduced with bempedoic acid treatment at week 12, regardless of renal function.
• Overall pattern of adverse events was consistent in the renal function subgroups.

Results in patients with hypertension

• The placebo-corrected least squares (LS) mean percent change in LDL-c with bempedoic acid treatment at week 12 was -19.2% (95%CI:-20.9 to -17.5%, P<0.001) in patients with hypertension and -20.9% (95%CI:-24.2 to -17.5, P<0.001) in patients without hypertension (Pinteraction=0.37).
• Results for apoB levels were similar (-13.0%, 95%CI:-14.5 to -11.5%, P<0.001 for patients with hypertension and -15.3%, 95%CI:-18.0 to -12.6%, P<0.001 for patients without hypertension, Pinteraction=0.16).
• The safety profile of bempedoic acid was similar in patients with or without hypertension. There were no clinically meaningful changes in blood pressure.
• In the phase 2 trial, the placebo-corrected LS mean percent change in LDL-c was -24.2 (95%CI:-30.3 to -18.1, P<0.001) at week 6. Moreover, bempedoic acid was generally well-tolerated with a similar safety profile across treatment groups.

Conclusion

Bempedoic acid treatment resulted in significantly lowered LDL-c levels regardless of renal function status or presence of hypertension. Bempedoic acid was generally well tolerated in patients with stage 2 or stage 3a+b renal impairment, and in patients with hypertension.

– Our coverage of ACC.22 is based on the information provided during the congress –