Lipid-efficacy RCT · JAMA 2019
CLEAR Wisdom trial
Effect of Bempedoic Acid vs Placebo Added to Maximally Tolerated Statins on Low-Density Lipoprotein Cholesterol in Patients at High Risk for Cardiovascular Disease: The CLEAR Wisdom Randomized Clinical Trial.
The bottom line
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.
Primary lipid endpoint metUS status: US-approved
At a glance
- Medicine
- Bempedoic acid (180 mg) once daily (n=522)
- Compared with
- Placebo once daily (n=257)
- People
- 779
- Who took part
- Patients with atherosclerotic cardiovascular disease, heterozygous familial hypercholesterolemia, or both, with LDL-C level 70 mg/dL (1.8 mmol/L) or greater while receiving maximally tolerated lipid-lowering therapy
- Design
- Phase 3, randomized, double-blind, placebo-controlled clinical trial
- Follow-up
- 52 weeks (primary endpoint assessed at week 12; final follow-up date September 22, 2018)
- Main question
- Percent change from baseline in LDL-C level at week 12
Main result
Bempedoic acid lowered LDL-C levels significantly more than placebo at week 12 (-15.1% vs 2.4%, respectively; difference, -17.4% [95% CI, -21.0% to -13.9%]; P < .001)
Effect on LDL cholesterol
-15.1% vs 2.4%; difference, -17.4% [95% CI, -21.0% to -13.9%]; P < .001
Other results
Significant reductions with bempedoic acid vs placebo were observed at week 12 for non-high-density lipoprotein cholesterol (-10.8% vs 2.3%; difference, -13.0% [95% CI, -16.3% to -9.8%]; P < .001), total cholesterol (-9.9% vs 1.3%; difference, -11.2% [95% CI, -13.6% to -8.8%]; P < .001), apolipoprotein B (-9.3% vs 3.7%; difference, -13.0% [95% CI, -16.1% to -9.9%]; P < .001), and high-sensitivity C-reactive protein (median, -18.7% vs -9.4%; difference, -8.7% [asymptotic confidence limits, -17.2% to -0.4%]; P = .04)
Safety
Common adverse events included nasopharyngitis (5.2% vs 5.1% with bempedoic acid and placebo, respectively), urinary tract infection (5.0% vs 1.9%), and hyperuricemia (4.2% vs 1.9%)
In the trial's own words
“Bempedoic acid lowered LDL-C levels significantly more than placebo at week 12 (-15.1% vs 2.4%, respectively; difference, -17.4% [95% CI, -21.0% to -13.9%]; P < .001).”
Quoted from the abstract of JAMA 2019, checked word for word against PubMed. PubMed 31714986 · Full paper (DOI)
How this medicine works, where it stands and what it costs: Bempedoic acid (Nexletol, Nexlizet)
Common questions
What did the CLEAR Wisdom trial find?
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.
Who was in CLEAR Wisdom?
779 people. Patients with atherosclerotic cardiovascular disease, heterozygous familial hypercholesterolemia, or both, with LDL-C level 70 mg/dL (1.8 mmol/L) or greater while receiving maximally tolerated lipid-lowering therapy.
What was CLEAR Wisdom's main result?
Bempedoic acid lowered LDL-C levels significantly more than placebo at week 12 (-15.1% vs 2.4%, respectively; difference, -17.4% [95% CI, -21.0% to -13.9%]; P < .001)
How much did LDL cholesterol change in CLEAR Wisdom?
-15.1% vs 2.4%; difference, -17.4% [95% CI, -21.0% to -13.9%]; P < .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 Serenity (2019)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.
- 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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