# Ezetimibe

Drug · id `cardio:ezetimibe` · Cardiovascular Atlas · release `f6f6f1b6f50379ed` (public)

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Also called: Zetia

Browse, condition area: Coronary and vascular disease  

## In plain language

Ezetimibe is a cholesterol pill that is not a statin. It works by reducing how much cholesterol the gut absorbs. In IMPROVE-IT, adding it to a statin after an acute coronary syndrome lowered LDL cholesterol further and gave a small extra reduction in heart and blood-vessel events.

## Technical summary

RxNorm ingredient 341248. The IMPROVE-IT abstract describes it as a nonstatin drug that reduces intestinal cholesterol absorption. The evidence recorded is the combination with simvastatin; ezetimibe alone is not tested in this atlas.

## Claims, with the population each applies to

## Context: Adults hospitalised for an acute coronary syndrome in the previous 10 days with LDL cholesterol 50 to 100 mg/dL on lipid-lowering therapy (IMPROVE-IT)

Recipient: Adult; Population: Patients hospitalised for an acute coronary syndrome within the preceding 10 days, with LDL cholesterol 50 to 100 mg/dL if on lipid-lowering therapy or 50 to 125 mg/dL if not (abstract). The registry gives a minimum age of 18 years and all sexes.; Care setting: Hospital-recruited patients followed in a multicentre trial (abstract). Site list not read.; Geography: Not stated in the source (abstract). The registry record lists no countries.; Life stage: Adult, 18 years and older (registry minimum age); Follow-up: Median follow-up 6 years (abstract). The registry gives up to approximately 9 years as the outcome time frame.

### In IMPROVE-IT, 18,144 patients hospitalised for an acute coronary syndrome in the previous 10 days received simvastatin 40 mg with ezetimibe 10 mg or simvastatin 40 mg with placebo. The median time-weighted LDL cholesterol was 53.7 mg/dL with ezetimibe added and 69.5 mg/dL with simvastatin alone. At 7 years the Kaplan-Meier rate of the primary composite end point was 32.7% with ezetimibe and 34.7% with simvastatin alone (absolute difference 2.0 percentage points; hazard ratio 0.936, 95% CI 0.89 to 0.99; P=0.016). The abstract says muscle, gallbladder and hepatic adverse effects and cancer were similar in the two groups.

- Category: Effect
- Evidence stage: Interventional
- Certainty: Certainty not assessed
- Applies to: Recipient: Adult; Population: Patients hospitalised for an acute coronary syndrome within the preceding 10 days, with LDL cholesterol 50 to 100 mg/dL if on lipid-lowering therapy or 50 to 125 mg/dL if not (abstract). The registry gives a minimum age of 18 years and all sexes.; Care setting: Hospital-recruited patients followed in a multicentre trial (abstract). Site list not read.; Geography: Not stated in the source (abstract). The registry record lists no countries.; Life stage: Adult, 18 years and older (registry minimum age); Follow-up: Median follow-up 6 years (abstract). The registry gives up to approximately 9 years as the outcome time frame.
- Limitations: One randomised trial, double-blind, funded by Merck according to the abstract. The benefit is modest in absolute terms (2.0 percentage points at 7 years). The population was people after an acute coronary syndrome who took simvastatin 40 mg; the result is for adding ezetimibe to that statin, not for ezetimibe alone. Abstract only; the registry record lists Organon and Co as its current lead sponsor.
- Last checked: 2026-10-14
- Sources:
  1. Supports: Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.) <https://doi.org/10.1056/NEJMoa1410489>
     Locator: Abstract, METHODS, sentence 1, fragment 1 of 4: "We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and". Retrieved 2026-10-14T18:18:31Z. Source state: Current. Snapshot hash: 95ed7a7bcbbe090b707e2d1472e160f007bde63f724c65c03b53fb9cbcb93d57.
     How it applies: Abstract of the paper from PubMed; the full text was not read.
  2. Supports: Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.) <https://doi.org/10.1056/NEJMoa1410489>
     Locator: Abstract, METHODS, sentence 1, fragment 2 of 4: "had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter)". Retrieved 2026-10-14T18:18:31Z. Source state: Current. Snapshot hash: 95ed7a7bcbbe090b707e2d1472e160f007bde63f724c65c03b53fb9cbcb93d57.
     How it applies: LDL entry range on lipid-lowering therapy.
  3. Supports: Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.) <https://doi.org/10.1056/NEJMoa1410489>
     Locator: Abstract, METHODS, sentence 1, fragment 3 of 4: "if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter)". Retrieved 2026-10-14T18:18:31Z. Source state: Current. Snapshot hash: 95ed7a7bcbbe090b707e2d1472e160f007bde63f724c65c03b53fb9cbcb93d57.
     How it applies: LDL entry range when not on lipid-lowering therapy.
  4. Supports: Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.) <https://doi.org/10.1056/NEJMoa1410489>
     Locator: Abstract, METHODS, sentence 2: "The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy).". Retrieved 2026-10-14T18:18:31Z. Source state: Current. Snapshot hash: 95ed7a7bcbbe090b707e2d1472e160f007bde63f724c65c03b53fb9cbcb93d57.
     How it applies: The two treatment arms.
  5. Supports: Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.) <https://doi.org/10.1056/NEJMoa1410489>
     Locator: Abstract, METHODS, sentence 3, fragment 1 of 2: "The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization),". Retrieved 2026-10-14T18:18:31Z. Source state: Current. Snapshot hash: 95ed7a7bcbbe090b707e2d1472e160f007bde63f724c65c03b53fb9cbcb93d57.
     How it applies: Primary end point, first part.
  6. Supports: Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.) <https://doi.org/10.1056/NEJMoa1410489>
     Locator: Abstract, METHODS, sentence 3, fragment 2 of 2: "or nonfatal stroke.". Retrieved 2026-10-14T18:18:31Z. Source state: Current. Snapshot hash: 95ed7a7bcbbe090b707e2d1472e160f007bde63f724c65c03b53fb9cbcb93d57.
     How it applies: Primary end point, last part.
  7. Supports: Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.) <https://doi.org/10.1056/NEJMoa1410489>
     Locator: Abstract, METHODS, sentence 4: "The median follow-up was 6 years.". Retrieved 2026-10-14T18:18:31Z. Source state: Current. Snapshot hash: 95ed7a7bcbbe090b707e2d1472e160f007bde63f724c65c03b53fb9cbcb93d57.
     How it applies: Median follow-up.
  8. Supports: Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.) <https://doi.org/10.1056/NEJMoa1410489>
     Locator: Abstract, RESULTS, sentence 1, fragment 1 of 2: "The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group,". Retrieved 2026-10-14T18:18:31Z. Source state: Current. Snapshot hash: 95ed7a7bcbbe090b707e2d1472e160f007bde63f724c65c03b53fb9cbcb93d57.
     How it applies: Time-weighted LDL cholesterol, ezetimibe arm.
  9. Supports: Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.) <https://doi.org/10.1056/NEJMoa1410489>
     Locator: Abstract, RESULTS, sentence 1, fragment 2 of 2: "as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P&lt;0.001).". Retrieved 2026-10-14T18:18:31Z. Source state: Current. Snapshot hash: 95ed7a7bcbbe090b707e2d1472e160f007bde63f724c65c03b53fb9cbcb93d57.
     How it applies: Time-weighted LDL cholesterol, simvastatin-alone arm.
  10. Supports: Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.) <https://doi.org/10.1056/NEJMoa1410489>
     Locator: Abstract, RESULTS, sentence 2, fragment 1 of 2: "The Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group,". Retrieved 2026-10-14T18:18:31Z. Source state: Current. Snapshot hash: 95ed7a7bcbbe090b707e2d1472e160f007bde63f724c65c03b53fb9cbcb93d57.
     How it applies: Kaplan-Meier event rate at 7 years, ezetimibe arm.
  11. Supports: Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.) <https://doi.org/10.1056/NEJMoa1410489>
     Locator: Abstract, RESULTS, sentence 2, fragment 2 of 2: "as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P=0.016).". Retrieved 2026-10-14T18:18:31Z. Source state: Current. Snapshot hash: 95ed7a7bcbbe090b707e2d1472e160f007bde63f724c65c03b53fb9cbcb93d57.
     How it applies: Event rate, comparator arm, and hazard ratio.
  12. Supports: Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.) <https://doi.org/10.1056/NEJMoa1410489>
     Locator: Abstract, RESULTS, sentence 3: "Rates of prespecified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups.". Retrieved 2026-10-14T18:18:31Z. Source state: Current. Snapshot hash: 95ed7a7bcbbe090b707e2d1472e160f007bde63f724c65c03b53fb9cbcb93d57.
     How it applies: Adverse effects and cancer were similar.
  13. Background: Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.) <https://doi.org/10.1056/NEJMoa1410489>
     Locator: Abstract, CONCLUSIONS, sentence 3: "(Funded by Merck; IMPROVE-IT ClinicalTrials.gov number, NCT00202878.).". Retrieved 2026-10-14T18:18:31Z. Source state: Current. Snapshot hash: 95ed7a7bcbbe090b707e2d1472e160f007bde63f724c65c03b53fb9cbcb93d57.
     How it applies: Funding note in the abstract.
  14. Supports: IMPROVE-IT: Examining Outcomes in Subjects With Acute Coronary Syndrome: Vytorin (Ezetimibe/Simvastatin) vs Simvastatin (P04103) (Registry, edition ClinicalTrials.gov API v2 record, last update posted 2024-06-18.) <https://clinicaltrials.gov/study/NCT00202878>
     Locator: protocolSection.designModule.enrollmentInfo.count: "18144". Retrieved 2026-10-14T18:18:31Z. Source state: Current. Snapshot hash: 591576a2ffb6fc2d9789d27fc116ad9587258642700ce74649121e0d84936c81.
     How it applies: Registry enrollment count, equal to the abstract.

## Connected pages

- Added to a statin after acute coronary syndrome: Coronary artery disease (`cardio:coronary-artery-disease`) [a claim, not a settled fact; see claim `cardio:claim-improve-it-ezetimibe-added-to-statin` and its context]
- Added to a statin in IMPROVE-IT: Statins (`cardio:statins`)
- Files under this front: Medicines (`cardio:front-medicines`)
- Investigated in: IMPROVE-IT (ezetimibe added to simvastatin after acute coronary syndrome) (`cardio:improve-it`)

## Provenance

Content hash: 3ebc25dddaa588e0a0b4f5eb7df4e71b858427850ebdb5b02086433c2a338065
Last substantive edit: 2026-10-14
Evidence last checked: 2026-10-14