Cardiovascular outcome trial · N Engl J Med 2023
CLEAR Outcomes trial
Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients.
The bottom line
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.
BenefitUS status: US-approved
At a glance
- Medicine
- oral bempedoic acid, 180 mg daily
- Compared with
- placebo
- People
- 13,970
- Who took part
- statin-intolerant patients with, or at high risk for, cardiovascular disease
- Design
- double-blind, randomized, placebo-controlled trial
- Follow-up
- median 40.6 months
- Main question
- four-component composite of major adverse cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization)
Main result
819 patients [11.7%] vs. 927 [13.3%]; hazard ratio, 0.87; 95% confidence interval [CI], 0.79 to 0.96; P = 0.004
Effect on LDL cholesterol
reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg per deciliter; the observed difference in the percent reductions was 21.1 percentage points in favor of bempedoic acid
Other results
Bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause. Composite of death from cardiovascular causes, nonfatal stroke, or nonfatal myocardial infarction: 575 [8.2%] vs. 663 [9.5%]; hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P = 0.006; fatal or nonfatal myocardial infarction: 261 [3.7%] vs. 334 [4.8%]; hazard ratio, 0.77; 95% CI, 0.66 to 0.91; P = 0.002; coronary revascularization: 435 [6.2%] vs. 529 [7.6%]; hazard ratio, 0.81; 95% CI, 0.72 to 0.92; P = 0.001
Safety
The incidences of gout and cholelithiasis were higher with bempedoic acid than with placebo (3.1% vs. 2.1% and 2.2% vs. 1.2%, respectively), as were the incidences of small increases in serum creatinine, uric acid, and hepatic-enzyme levels.
In the trial's own words
“The incidence of a primary end-point event was significantly lower with bempedoic acid than with placebo (819 patients [11.7%] vs. 927 [13.3%]; hazard ratio, 0.87; 95% confidence interval [CI], 0.79 to 0.96; P = 0.004)”
Quoted from the abstract of N Engl J Med 2023, checked word for word against PubMed. PubMed 36876740 · Full paper (DOI)
How this medicine works, where it stands and what it costs: Bempedoic acid (Nexletol, Nexlizet)
Common questions
What did the CLEAR Outcomes trial find?
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.
Who was in CLEAR Outcomes?
13,970 people. statin-intolerant patients with, or at high risk for, cardiovascular disease.
What was CLEAR Outcomes's main result?
819 patients [11.7%] vs. 927 [13.3%]; hazard ratio, 0.87; 95% confidence interval [CI], 0.79 to 0.96; P = 0.004
How much did LDL cholesterol change in CLEAR Outcomes?
reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg per deciliter; the observed difference in the percent reductions was 21.1 percentage points in favor of bempedoic acid
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 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.
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