BEMPEDOIC ACID (NEXLETOL®)













  • Values are average percent change from baseline
  • 95% of patients had established ASCVD and 5% had HeFH
  • Average baseline LDL level was 103 mg/dl
  • Reference [1]
Effects of Bempedoic Acid on Lipid Parameters in Patients with HeFH and/or ASCVD on Maximally Tolerated Statin Therapy at 12 weeks
Bempedoic acid 180 mg
(N=1488)		 Placebo
(N=742)
Total -10% +1%
LDL -17% +2%
Non-HDL cholesterol -12% +2%
Apo B -9% +3%



CLEAR Study - Bempedoic acid vs Placebo for CVD outcomes in Statin-intolerant Patients, 2023 (NEJM) [PubMed abstract]
  • The CLEAR study enrolled 13,970 patients with or at high risk for CVD who were unable or unwilling to receive statins owing to adverse effects
Main inclusion criteria
  • Adults 18 - 85 years old
  • Previous CVD event or high risk for CVD
  • Unable or unwilling to receive statins (low-dose statins were allowed)
Main exclusion criteria
  • Triglycerides > 500 mg/dl
  • GFR < 30 ml/min
  • CVD event within 90 days
  • NYHA class IV heart failure
  • Uncontrolled hypertension
Baseline characteristics
  • Average age 65 years
  • Previous CVD event - 70%
  • Average LDL - 139 mg/dl
  • Diabetes - 46%
  • Using low-dose statin - 23%
Randomized treatment groups
  • Group 1 (6992 patients): Bempedoic acid 180 mg once daily
  • Group 2 (6978 patients): Placebo
  • Other lipid-lowering therapies, including low-dose statins (e.g. atorvastatin < 10 mg), ezetimibe, niacin, bile acid sequestrants, fibrates, and PCSK9 inhibitors were allowed
  • If LDL levels rose above 25% of baseline after 6 months, other lipid-lowering therapies could be adjusted
Primary outcome: Composite of major adverse cardiovascular events, defined as death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization, as assessed in a time-to-first-event analysis
Results

Duration: Median 40.6 months
Outcome Bempedoic acid Placebo Comparisons
Primary outcome 11.7% 13.3% p=0.004
Myocardial infarction 3.7% 4.8% p=0.002
Stroke 1.9% 2.3% p=0.16
Coronary revascularazation 6.2% 7.6% p=0.001
Death from CV causes 3.8% 3.7% Diff 1.04 95%CI [0.88 to 1.24]
Overall mortality 6.2% 6.0% Diff 1.03 95%CI [0.90 to 1.18]
Change in LDL at 6 months -21.1% -0.8% Diff -20.3 95%CI [-21.1 to -19.5]
Renal impairment 11.5% 8.6% N/A
Elevated liver enzymes 4.5% 3.0% N/A
  • Besides liver enzyme elevations and renal impairment, other adverse events were similar between groups, including myalgias (bempedoic acid - 5.6%, placebo - 6.8%)

Findings: Among statin-intolerant patients, treatment with bempedoic acid was associated with a lower risk of major adverse cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization).




  • Data is from trials lasting 52 weeks
  • Reference [1]
Side effect Bempedoic acid + statin
(N=2009)		 Placebo + statin
(N=999)
Upper respiratory tract infection 4.5% 4.0%
Muscle spasms 3.6% 2.3%
Hyperuricemia 3.5% 1.1%
Back pain 3.3% 2.2%
Abdominal pain or discomfort 3.1% 2.2%
Bronchitis 3.0% 2.5%
Pain in extremity 3.0% 1.7%
Anemia 2.8% 1.9%
Elevated liver enzymes 2.1% 0.8%
Atrial fibrillation 1.7% 1.1%
New-onset BPH in men 1.3% 0.1%