Lipid-efficacy RCT · N Engl J Med 2019
CLEAR Harmony trial
Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol.
The bottom line
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.
Primary safety endpoint met; LDL-C loweredUS status: US-approved
At a glance
- Medicine
- Bempedoic acid
- Compared with
- Placebo (added to maximally tolerated statin therapy)
- People
- 2,230
- Who took part
- Patients with atherosclerotic cardiovascular disease, heterozygous familial hypercholesterolemia, or both, with LDL cholesterol ≥70 mg/dL while receiving maximally tolerated statin therapy with or without additional lipid-lowering therapy
- Design
- Randomized, controlled trial (2:1 randomization), 52 weeks
- Follow-up
- 52 weeks
- Main question
- Safety (incidence of adverse events); principal secondary (efficacy) end point was percentage change in LDL cholesterol level at week 12
Main result
Incidence of adverse events: 1167 of 1487 patients (78.5%) in the bempedoic acid group and 584 of 742 (78.7%) in the placebo group; did not differ substantially between groups
Effect on LDL cholesterol
Reduced mean LDL cholesterol by 19.2 mg/dL, a -16.5% change from baseline; difference vs. placebo -18.1 percentage points (95% CI, -20.0 to -16.1; P<0.001)
Other results
Not reported in abstract (principal secondary/efficacy endpoint was percentage change in LDL cholesterol at week 12; no mortality data reported)
Safety
Serious adverse events: 216 patients (14.5%) bempedoic acid vs. 104 (14.0%) placebo; adverse events leading to discontinuation: 162 (10.9%) vs. 53 (7.1%); gout: 18 patients (1.2%) vs. 2 (0.3%)
In the trial's own words
“At week 12, bempedoic acid reduced the mean LDL cholesterol level by 19.2 mg per deciliter, representing a change of -16.5% from baseline (difference vs. placebo in change from baseline, -18.1 percentage points; 95% confidence interval, -20.0 to -16.1; P<0.001).”
Quoted from the abstract of N Engl J Med 2019, checked word for word against PubMed. PubMed 30865796 · Full paper (DOI)
How this medicine works, where it stands and what it costs: Bempedoic acid (Nexletol, Nexlizet)
Common questions
What did the CLEAR Harmony trial find?
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.
Who was in CLEAR Harmony?
2,230 people. Patients with atherosclerotic cardiovascular disease, heterozygous familial hypercholesterolemia, or both, with LDL cholesterol ≥70 mg/dL while receiving maximally tolerated statin therapy with or without additional lipid-lowering therapy.
What was CLEAR Harmony's main result?
Incidence of adverse events: 1167 of 1487 patients (78.5%) in the bempedoic acid group and 584 of 742 (78.7%) in the placebo group; did not differ substantially between groups
How much did LDL cholesterol change in CLEAR Harmony?
Reduced mean LDL cholesterol by 19.2 mg/dL, a -16.5% change from baseline; difference vs. placebo -18.1 percentage points (95% CI, -20.0 to -16.1; P<0.001)
Related trials
- 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 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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