CLEAR Harmony
Trial question
What is the role of bempedoic acid in patients with increased LDL-C levels?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
27.0% female
73.0% male
N = 2230
2230 patients (602 female, 1628 male).
Inclusion criteria: patients taking the maximum tolerated dose of statin therapy with ASCVD.
Key exclusion criteria: use of gemfibrozil or simvastatin at doses > 40 mg/day; total fasting triglyceride ≥ 500 mg/dL; BMI ≥ 50 kg/m²; use of a proprotein convertase subtilisin/kexin 9 within the past 4 weeks.
Interventions
N=1488 bempedoic acid (at an oral dose of 180 mg once daily).
N=742 placebo (matching placebo tablet taken PO once daily).
Primary outcome
Adverse events
78.5%
78.7%
78.7 %
59.0 %
39.4 %
19.7 %
0.0 %
Bempedoic
acid
Placebo
No significant
difference ↔
No significant difference in adverse events (78.5% vs. 78.7%; ARD -0.2, 95% CI -3.39 to 2.99).
Secondary outcomes
Significant decrease in change in the LDL-C level at week 12 (-16.5% vs. 1.6%; ARD -18.1, 95% CI -20 to -16.1).
Significant decrease in change in the LDL-C level at week 24 (-14.9% vs. 1.2%; ARD -16.1, 95% CI -18.2 to -14).
Significant decrease in total cholesterol level elevation at week 12 (-10.3% vs. 0.8%; ARD -11.1, 95% CI -12.5 to -9.8).
Safety outcomes
No significant difference in serious adverse events.
Significant differences in adverse events leading to discontinuation of trial agent (10.9% vs. 7.1%), gout (1.2% vs. 0.3%), new-onset or worsening diabetes (3.3% vs. 5.4%).
Conclusion
In patients taking the maximum tolerated dose of statin therapy with ASCVD, bempedoic acid was not superior to placebo with respect to adverse events.
Reference
Kausik K Ray, Harold E Bays, Alberico L Catapano et al. Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol. N Engl J Med. 2019 Mar 14;380(11):1022-1032.
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