Lipid-efficacy RCT · J Am Heart Assoc 2019
CLEAR Serenity trial
Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia and Statin Intolerance.
The bottom line
In statin-intolerant patients with high cholesterol, bempedoic acid 180 mg daily significantly lowered LDL cholesterol and other atherogenic lipids and inflammation markers compared with placebo, with a safety and muscle-symptom profile similar to or better than placebo.
Primary lipid endpoint metUS status: US-approved
At a glance
- Medicine
- Bempedoic acid 180 mg once daily
- Compared with
- Placebo once daily
- People
- 345
- Who took part
- Patients with hypercholesterolemia and a history of intolerance to at least 2 statins (1 at the lowest available dose); mean age 65.2 years, mean baseline LDL-C 157.6 mg/dL, 93% with history of statin-associated muscle symptoms
- Design
- Phase 3, double-blind, placebo-controlled, randomized 2:1
- Follow-up
- 24 weeks (primary endpoint assessed at week 12)
- Main question
- Mean percent change from baseline to week 12 in low-density lipoprotein cholesterol
Main result
Placebo-corrected difference in LDL-C, -21.4% [95% CI, -25.1% to -17.7%]; P<0.001
Effect on LDL cholesterol
Placebo-corrected difference in LDL-C, -21.4% [95% CI, -25.1% to -17.7%]; P<0.001
Other results
Significant reductions vs placebo in non-HDL cholesterol (-17.9%), total cholesterol (-14.8%), apolipoprotein B (-15.0%), and high-sensitivity C-reactive protein (-24.3%); P<0.001 for all comparisons.
Safety
Bempedoic acid was safe and well tolerated. Myalgia (most common muscle-related adverse event) occurred in 4.7% of bempedoic acid patients vs 7.2% of placebo patients.
In the trial's own words
“Bempedoic acid treatment significantly reduced low-density lipoprotein cholesterol from baseline to week 12 (placebo-corrected difference, -21.4% [95% CI, -25.1% to -17.7%]; P<0.001). Significant reductions with bempedoic acid versus placebo were also observed in non-high-density lipoprotein cholesterol (-17.9%), total cholesterol (-14.8%), apolipoprotein B (-15.0%), and high-sensitivity C-reactive protein (-24.3%; P<0.001 for all comparisons). Bempedoic acid was safe and well tolerated. The most common muscle-related adverse event, myalgia, occurred in 4.7% and 7.2% of patients who received bempedoic acid or placebo, respectively.”
Quoted from the abstract of J Am Heart Assoc 2019, checked word for word against PubMed. PubMed 30922146 · Full paper (DOI)
How this medicine works, where it stands and what it costs: Bempedoic acid (Nexletol, Nexlizet)
Common questions
What did the CLEAR Serenity trial find?
In statin-intolerant patients with high cholesterol, bempedoic acid 180 mg daily significantly lowered LDL cholesterol and other atherogenic lipids and inflammation markers compared with placebo, with a safety and muscle-symptom profile similar to or better than placebo.
Who was in CLEAR Serenity?
345 people. Patients with hypercholesterolemia and a history of intolerance to at least 2 statins (1 at the lowest available dose); mean age 65.2 years, mean baseline LDL-C 157.6 mg/dL, 93% with history of statin-associated muscle symptoms.
What was CLEAR Serenity's main result?
Placebo-corrected difference in LDL-C, -21.4% [95% CI, -25.1% to -17.7%]; P<0.001
How much did LDL cholesterol change in CLEAR Serenity?
Placebo-corrected difference in LDL-C, -21.4% [95% CI, -25.1% to -17.7%]; P<0.001
Related trials
- CLEAR Harmony (2019)In statin-treated patients with ASCVD or familial hypercholesterolemia, adding bempedoic acid significantly lowered LDL cholesterol compared with placebo over 52 weeks without increasing overall adverse events, though it was linked to more treatment discontinuations and gout.
- CLEAR Wisdom (2019)Adding bempedoic acid to maximally tolerated statin therapy significantly lowered LDL-C and other atherogenic lipid markers compared with placebo over 12 weeks, though cardiovascular outcome benefit was not assessed in this trial.
- CLEAR Outcomes (2023)In statin-intolerant patients, bempedoic acid significantly lowered LDL cholesterol and reduced major adverse cardiovascular events compared with placebo, though it did not significantly reduce stroke or death, and was associated with more gout, gallstones, and modest increases in creatinine, uric acid, and liver enzymes.
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