Bempedoic acid improves lipid, glycaemic parameters regardless of metabolic status
Data presented at AHA 2021 demonstrated the efficacy and safety of bempedoic acid for improving lipid and glycaemic parameters and hsCRP irrespective of metabolic status.
“[In our study,] bempedoic acid significantly lowered LDL-C*, TC*, non-HDL-C*, apolipoprotein B, and hsCRP* vs placebo. These reductions were all highly statistically significant regardless of baseline metabolic status,” said Dr Michael Shapiro from the Wake Forest University School of Medicine, Winston-Salem, North Carolina, US, during his virtual presentation. “Moreover, bempedoic acid lowered HbA1c** and FPG** levels to a greater extent in patients with vs without metabolic syndrome (MetS).”
Week 12 saw significant drops in LDL-C with bempedoic acid vs placebo in patients with and without MetS (least squares mean [LSM] percent change, –19.1 and –16.4; pinteraction=0.0472). “[While both arms showed reductions, the] statistically significant interaction between LDL-C-lowering and baseline metabolic status indicates that individuals with MetS tended to enjoy greater LDL-C reduction with bempedoic acid vs those without MetS,” explained Shapiro.
The LDL-C reductions with bempedoic acid were also significant when compared against placebo (placebo‑corrected difference, −22.3 [with MetS] and −18.4 [without MetS]; p<0.0001 for both). [AHA 2021, abstract 267]
Baseline secondary lipid parameters also dropped with bempedoic acid vs placebo at week 12, both among those with (placebo-corrected LSM percent change, –13.2, –14.7, and –13.6 for TC, non-HDL-C, and apolipoprotein B, respectively) and without MetS (placebo-corrected LSM percent change, –12.4, –15.9, and –14.5, respectively; p<0.0001 for all). “However, there was no interaction between the lowering of any of these parameters and baseline metabolic status,” noted Shapiro.
In patients with MetS, week 12 saw modest increases in triglycerides in both arms, more so with bempedoic acid vs placebo (median percent change, 2.3 vs 0.7; p<0.0001). Among those without MetS, triglycerides dropped with bempedoic acid and increased with placebo (median percent change, –0.7 vs 3.0; p=0.020). “[It should be noted however that the] absolute changes in triglycerides were relatively small and generally consistent with those observed in bempedoic acid phase III studies,” Shapiro pointed out.
Other parameters, safety
Absolute reductions in glycaemic parameters were greater with bempedoic acid vs placebo among those with MetS (LSM change, –0.06 vs 0.01; p<0.0001 [HbA1c] and –0.4 vs 2.0; p=0.0022 [FPG]). For those without MetS, changes were not significantly different between bempedoic acid and placebo (LSM change, –0.02 vs –0.02; p=0.9513 and 1.2 vs 1.0; p=0.6784).
Median percent changes in hsCRP dropped substantially as well with bempedoic acid vs placebo irrespective of metabolic status (–26.9 vs –5.9 [with MetS] and –15.8 vs 4.8 [without MetS]; p<0.0001 for both).
The rates of treatment-emergent adverse events (TEAEs) with bempedoic acid was comparable in both subgroups of patients with and without MetS (71 percent vs 75 percent), as was the rates of the most common TEAEs such as nasopharyngitis (6 percent vs 9 percent), myalgia (4 percent vs 6 percent), and arthralgia (4 percent vs 5 percent). “[These suggest that] bempedoic acid was generally well-tolerated with comparable safety profiles in patients with and with MetS,” said Shapiro.
This study pooled data from four phase III studies (n=3,623). After excluding individuals with diabetes (n=1,114), the remaining participants (mean age 65 years, 66 percent male) were categorized as having MetS (n=936) or not (n=1,573). Participants were randomized 2:1 to receive either bempedoic acid or placebo for 12–52 weeks.
Patients with MetS had a higher prevalence of hypertension than those without (85 percent vs 65 percent) and had a higher BMI (32 vs 27 kg/m2) as would be expected, noted Shapiro. “Importantly, baseline statin intensity was similar in each group irrespective of metabolic status or whether participants were randomized to bempedoic acid or placebo.”