EZETIMIBE (ZETIA®)

















  • Values are average percent change from baseline, except triglycerides which is median percent change from baseline
  • Reference [1]
Effect of ezetimibe on cholesterol in a 12-week trial
Ezetimibe 10 mg
(N=1288)
Placebo
(N=431)
Total -13% 0%
LDL -18% +1%
Triglycerides -8% 0%
HDL +1% -2%

  • Values are average percent change from baseline, except triglycerides which is median percent change from baseline
  • Statins in trial - 40% atorvastatin, 31% simvastatin, 29% others (pravastatin, fluvastatin, cerivastatin, lovastatin)
  • Reference [1]
Effects of ezetimibe when added to statins in an 8-week trial
Ezetimibe + statin
(N=379)
Placebo + statin
(N=390)
Total -17% -2%
LDL -25% -4%
Triglycerides -14% -3%
HDL +3% +1%




IMPROVE-IT Trial - Ezetimibe vs Placebo added to Simvastatin for the Secondary Prevention of CVD, NEJM (2015) [PubMed abstract]
  • The IMPROVE-IT study enrolled 18,144 patients with acute coronary syndrome
Main inclusion criteria
  • Age ≥ 50 years
  • Hospitalized within previous 10 days for ACS
  • LDL level ≥ 50 mg/dl
  • LDL level ≤ 125 mg/dl (no treatment) or ≤ 100 mg/dl (with treatment)
Main exclusion criteria
  • Planned CABG
  • Using potent statin (equivalent to > 40 mg simvastatin)
  • CrCl < 30 ml/min
  • Active liver disease
Baseline characteristics
  • Average age 64 years
  • Average LDL - 94 mg/dl
  • Previous heart attack - 21%
  • Prior statin use - 34.5%
  • Index event: STEMI - 29% | NSTEMI - 47% | Unstable angina - 24%
Randomized treatment groups
  • Group 1 (9077 patients) - Placebo + Simvastatin 40 mg once daily
  • Group 2 (9067 patients) - Ezetimibe 10 mg + Simvastatin 40 mg once daily
Primary outcome: Composite of death from cardiovascular disease, a major coronary event (heart attack, documented unstable angina requiring hospital admission, or coronary revascularization occurring at least 30 days after randomization), or nonfatal stroke
Results

Duration: 7 years
Outcome Placebo Ezetimibe Comparisons
Primary outcome 34.7% 32.7% HR 0.936, 95%CI [0.89 to 0.99], p=0.016
Overall mortality 15.3% 15.4% HR 0.99, 95%CI [0.91 to 1.07], p=0.78
Any myocardial infarction 14.8% 13.1% HR 0.87, 95%CI [0.80 to 0.95], p=0.002
Any stroke 4.8% 4.2% HR 0.86, 95%CI [0.73 to 1.00], p=0.05
Average LDL level (median time-weighted) 69.5 mg/dl 53.7 mg/dl N/A
  • The incidence of adverse events including muscle and liver toxicity, cholecystectomy, and cancer were similar between the two groups

Findings: When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit.






  • Numbers are percent of patients in controlled trials
  • Reference [1]
Consecutive liver enzyme elevations (≥ 3 X ULN)
Ezetimibe monotherapy 0.5%
Placebo 0.3%
Ezetimibe + statin 1.3%
Placebo + statin 0.4%
















Ezetimibe (Zetia®)

Dosage forms

Tablet
  • 10 mg

Dosing

High cholesterol
  • 10 mg once daily
  • May take without regard to food

Generic / Price

- YES/$

Ezetimibe + simvastatin (Vytorin®)

Dosage forms

Tablet
  • Ezetimibe - Simvastatin
    • 10 mg - 10 mg
    • 10 mg - 20 mg
    • 10 mg - 40 mg
    • 10 mg - 80 mg

Dosing

High cholesterol
  • Starting: 10/10 - 10/20 mg once daily in the evening
  • Maintenance: 10/10 - 10/40 mg once daily in the evening
  • Max: 10/40 mg once daily
  • For patients requiring > 55% LDL reduction, recommended starting dose is 10/40 mg/day
  • Due to increased risk of myopathy, the 10/80 mg dose should be restricted to patients who have been taking 10/80 mg chronically (> 12 months) without evidence of muscle toxicity
  • May take without regard to food

Generic / Price

- YES/$$-$$$

Roszet® (rosuvastatin + ezetimibe)

Dosage forms

Tablet
  • Rosuvastatin - Ezetimibe
    • 5 mg - 10 mg
    • 10 mg - 10 mg
    • 20 mg - 10 mg
    • 40 mg - 10 mg

Dosing

High cholesterol
  • Dosing: 5/10 mg - 40/10 mg once daily
  • Asian patients: starting dose should be 5/10 mg once daily. Consider risks/benefits of doses > 20/10 mg. Exposure to rosuvastatin is higher in Asian patients (see statins in Asian patients for more).
  • Kidney disease:
    • CrCl ≥ 30 ml/min: no dose adjustment necessary
    • CrCl < 30 ml/min: recommended starting dose is 5/10 mg once daily. Do not exceed 10/10 mg once daily.
  • May take without regard to food
  • Do not crush, dissolve, or chew tablets

Generic / Price

- NO/$$$$

Bempedoic acid + Ezetimibe (Nexlizet®)

Dosage forms

Tablet
  • Bempedoic acid - Ezetimibe
    • 180 mg - 10 mg

Dosing

High cholesterol
  • 180/10 mg once daily
  • May take without regard to food
  • Swallow tablet whole
  • Check lipids 8 - 12 weeks after starting
  • Nexlizet should be taken with with maximally tolerated statin therapy

Generic / Price

- NO/$$$$