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CompletedNCT00202878Updated Jun 18, 2024Results posted

IMPROVE-IT: Examining Outcomes in Subjects With Acute Coronary Syndrome: Vytorin (Ezetimibe/Simvastatin) vs Simvastatin (P04103)

A Phase 3 interventional study of ezetimibe/simvastatin and simvastatin in Hypercholesterolemia and Myocardial Infarction, sponsored by Organon and Co. Completed. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-06-18.

Sponsored by Organon and Co · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
18,144
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

This is a randomized, active-control, double-blind study of subjects with stabilized high-risk acute coronary syndrome (ACS). The primary objective is to evaluate the clinical benefit of Ezetimibe/Simvastatin Combination 10/40 (single tablet, under the brand VYTORIN in the United States) compared with Simvastatin 40 mg. As per the original protocol, if low-density lipoprotein cholesterol (LDL-C) response was inadequate, the dose of simvastatin in the VYTORIN arm or simvastatin arm, could be increased to 80 mg (Note: per June 2011 protocol amendment, criteria for continued use of 80 mg simvastatin were modified and new increases of simvastatin dose to 80 mg were stopped). Clinical benefit will be defined as the reduction in the risk of the occurrence of the composite endpoint of cardiovascular (CV) death, major coronary events, and stroke.

02

Conditions studied

  • Hypercholesterolemia
  • Myocardial Infarction

Keywords

  • hypercholesterolemia
  • myocardial infarction
  • cholesterol
  • randomized controlled trials
  • acute coronary syndrome
  • angina
03

In context

Hypercholesterolemia

1,267 studies on the registry are indexed under Hypercholesterolemia; 105 are open to participants now.

This study's enrollment of 18,144 is above the median of 100 across 1,015 interventional studies indexed under Hypercholesterolemia.

Browse Hypercholesterolemia studies →

Lead sponsor

Organon and Co is the lead sponsor of 505 studies on the registry; none are open to participants now.

Of its 22 completed or terminated interventional studies of FDA-regulated products, 18 (82%) have results posted.

Browse Organon & Co. studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Clinically stable participants may be eligible to enroll within 10 days following hospital admission with high-risk acute coronary syndrome (either ST-elevation myocardial infarction [STEMI] or Non-STEMI or unstable angina)
  • Participants not taking a statin must have an LDL-C of 125 mg/dl or less. Participants taking a statin must have an LDL-C of 100 mg/dl or less.

Exclusion criteria

Exclusion Criteria:

  • Pregnant or lactating woman, or intending to become pregnant
  • Participant with active liver disease or persistent unexplained serum transaminase elevation
  • History of alcohol or drug abuse
  • History of sensitivity to statin or ezetimibe
  • A participant for whom discontinuation of existing lipid lowering regimen poses an unacceptable risk.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
18,144 participants (actual)

Study arms

  • Experimental
    ezetimibe/simvastatin

    One Ezetimibe 10 mg/simvastatin 40 mg combination tablet and two simvastatin 40 mg placebo tablets once per day.

    Drug: ezetimibe/simvastatin · Drug: Placebo for simvastatin 40 mg

  • Active comparator
    simvastatin

    One simvastatin 40 mg tablet, one ezetimibe/simvastatin combination 10/40 placebo tablet and one simvastatin 40 mg placebo tablet once per day.

    Drug: simvastatin · Drug: Placebo for simvastatin 40 mg · Drug: Placebo for ezetimibe 10 mg/simvastatin 40 mg combination

Interventions

  • Drugezetimibe/simvastatin

    Ezetimibe/simvastatin 10/40 mg per day from randomization through the end of participation. As per the original protocol, if LDL-C response was inadequate, the dose of simvastatin in the VYTORIN arm or simvastatin arm, could be increased to 80 mg (Note: per June 2011 protocol amendment, criteria for continued use of 80 mg simvastatin were modified and new increases of simvastatin dose to 80 mg were stopped).

    Also known as: Vytorin, Inegy

  • Drugsimvastatin

    Simvastatin 40 mg per day from randomization through the end of participation. As per the original protocol, if LDL-C response was inadequate, the dose of simvastatin in the VYTORIN arm or simvastatin arm, could be increased to 80 mg (Note: per June 2011 protocol amendment, criteria for continued use of 80 mg simvastatin were modified and new increases of simvastatin dose to 80 mg were stopped).

    Also known as: Zocor

  • DrugPlacebo for simvastatin 40 mg

    one or two tablets orally daily

  • DrugPlacebo for ezetimibe 10 mg/simvastatin 40 mg combination

    one tablet orally daily.

06

What researchers measure

Primary outcomes

  1. Time to First Occurrence of Cardiovascular Death, Major Coronary Event, or Non-fatal Stroke (Kaplan-Meier Estimate of Percentage of Participants Experiencing a Qualifying Event)

    The time (in months) from study start to the first occurrence of any of the following clinical outcomes was recorded: cardiovascular death, major coronary Event (non-fatal myocardial infarction \[MI\], documented unstable angina \[UA\] requiring hospitalization, or coronary revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) ≥ 30 days after randomization), or non-fatal Stroke. A Clinical Endpoints Committee (CEC) reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or who were lost to follow-up and had no event were censored at the time of last available information (last study visit). The Kaplan-Meier estimate reports the percentage of participants who experienced cardiovascular death, major coronary event, or non-fatal stroke within 7 years from randomization.

    Time frame: Up to approximately 9 years

Secondary outcomes

  1. Time to First Occurrence of Death From Any Cause, Major Coronary Event, or Non-fatal Stroke (Kaplan-Meier Estimate of Percentage of Participants Experiencing a Qualifying Event)

    The time (in months) from study start to the first occurrence of any of the following clinical outcomes was recorded: death from any cause, major coronary event (non-fatal myocardial infarction, documented unstable angina requiring hospitalization, or coronary revascularization with percutaneous coronary intervention or coronary artery bypass grafting ≥ 30 days after randomization), or non-fatal stroke. A Clinical Endpoints Committee (CEC) reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or who were lost to follow-up and had no event were censored at the time of last available information (last study visit). The Kaplan-Meier estimate reports the percentage of participants who experienced death from any cause, major coronary event, or non-fatal stroke within 7 years from randomization.

    Time frame: Up to approximately 9 years

  2. Time to First Occurrence of Coronary Heart Disease (CHD) Death, Non-fatal MI, or Urgent Coronary Revascularization With PCI or CABG ≥ 30 Days After Randomization (Kaplan-Meier Estimate of Percentage of Participants Experiencing a Qualifying Event)

    The time (in months) from study start to the first occurrence of any of the following clinical outcomes was recorded: CHD death, non-fatal MI, or urgent coronary revascularization with PCI or CABG ≥ 30 days after randomization. A Clinical Endpoints Committee (CEC) reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or who were lost to follow-up and had no event were censored at the time of last available information (last study visit). The Kaplan-Meier estimate reports the percentage of participants who experienced CHD death, non-fatal MI, or urgent coronary revascularization with PCI or CABG ≥ 30 days after randomization within 7 years from randomization.

    Time frame: Up to approximately 9 years

  3. Time to First Occurrence of CV Death, Nonfatal MI, UA With Hospitalization, All Revascularization Occurring ≥30 Days After Randomization, and Non-fatal Stroke (Kaplan-Meier Estimate of Percentage of Participants Experiencing a Qualifying Event)

    The time (in months) from study start to the first occurrence of any of the following clinical outcomes was recorded: CV death, non-fatal MI, documented UA that requires admission into a hospital, all revascularization (including non-coronary) occurring at least 30 days after randomization, and non-fatal stroke. A Clinical Endpoints Committee (CEC) reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or who were lost to follow-up and had no event were censored at the time of last available information (last study visit). The Kaplan-Meier estimate reports the percentage of participants who experienced CV death, non-fatal MI, unstable angina with hospitalization, all revascularization occurring ≥ 30 days after randomization, and non-fatal stroke within 7 Years from randomization.

    Time frame: Up to approximately 9 years

07

Results

Posted Sep 30, 2015

Participant flow

Adult men and women presenting with non-ST segment elevation myocardial infarction (NSTEMI) , STEMI, or hospitalized, documented unstable angina (UA) whom a percutaneous coronary intervention (PCI) was planned as management for the qualifying acute coronary syndrome (ACS) event were eligible for entry into the trial.

Participant flow — Overall Study
MilestoneEzetimibe/SimvastatinSimvastatin
Started90679077
Completed68686860
Not completed21992217
Withdrew: Death964968
Withdrew: Only vital status known357356
Withdrew: Lost to follow-up4449
Withdrew: Site closure3936
Withdrew: Withdrawal by subject795808

Outcome measures

PrimaryTime to First Occurrence of Cardiovascular Death, Major Coronary Event, or Non-fatal Stroke (Kaplan-Meier Estimate of Percentage of Participants Experiencing a Qualifying Event)

The time (in months) from study start to the first occurrence of any of the following clinical outcomes was recorded: cardiovascular death, major coronary Event (non-fatal myocardial infarction \[MI\], documented unstable angina \[UA\] requiring hospitalization, or coronary revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) ≥ 30 days after randomization), or non-fatal Stroke. A Clinical Endpoints Committee (CEC) reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or who were lost to follow-up and had no event were censored at the time of last available information (last study visit). The Kaplan-Meier estimate reports the percentage of participants who experienced cardiovascular death, major coronary event, or non-fatal stroke within 7 years from randomization.

Time frame:
Up to approximately 9 years
Reported as:
Number · Percentage of Participants
Time to First Occurrence of Cardiovascular Death, Major Coronary Event, or Non-fatal Stroke (Kaplan-Meier Estimate of Percentage of Participants Experiencing a Qualifying Event)
Percentage of ParticipantsEzetimibe/SimvastatinSimvastatin
Time to First Occurrence of Cardiovascular Death, Major Coronary Event, or Non-fatal Stroke (Kaplan-Meier Estimate of Percentage of Participants Experiencing a Qualifying Event)32.72 (31.63 to 33.85)34.67 (33.56 to 35.81)
Statistical analysis
  • Ezetimibe/Simvastatin vs Simvastatin · Cox proportional hazard model · p = 0.016 · Hazard ratio (hr): 0.936 · 95% CI 0.887 to 0.988Model includes events from randomization to last study visit.
SecondaryTime to First Occurrence of Death From Any Cause, Major Coronary Event, or Non-fatal Stroke (Kaplan-Meier Estimate of Percentage of Participants Experiencing a Qualifying Event)

The time (in months) from study start to the first occurrence of any of the following clinical outcomes was recorded: death from any cause, major coronary event (non-fatal myocardial infarction, documented unstable angina requiring hospitalization, or coronary revascularization with percutaneous coronary intervention or coronary artery bypass grafting ≥ 30 days after randomization), or non-fatal stroke. A Clinical Endpoints Committee (CEC) reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or who were lost to follow-up and had no event were censored at the time of last available information (last study visit). The Kaplan-Meier estimate reports the percentage of participants who experienced death from any cause, major coronary event, or non-fatal stroke within 7 years from randomization.

Time frame:
Up to approximately 9 years
Reported as:
Number · Percentage of Participants
Time to First Occurrence of Death From Any Cause, Major Coronary Event, or Non-fatal Stroke (Kaplan-Meier Estimate of Percentage of Participants Experiencing a Qualifying Event)
Percentage of ParticipantsEzetimibe/SimvastatinSimvastatin
Time to First Occurrence of Death From Any Cause, Major Coronary Event, or Non-fatal Stroke (Kaplan-Meier Estimate of Percentage of Participants Experiencing a Qualifying Event)38.65 (37.52 to 39.81)40.25 (39.11 to 41.41)
Statistical analysis
  • Ezetimibe/Simvastatin vs Simvastatin · Cox proportional hazard model · p = 0.035 · Hazard ratio (hr): 0.948 · 95% CI 0.903 to 0.996Model includes events from randomization to last study visit.
SecondaryTime to First Occurrence of Coronary Heart Disease (CHD) Death, Non-fatal MI, or Urgent Coronary Revascularization With PCI or CABG ≥ 30 Days After Randomization (Kaplan-Meier Estimate of Percentage of Participants Experiencing a Qualifying Event)

The time (in months) from study start to the first occurrence of any of the following clinical outcomes was recorded: CHD death, non-fatal MI, or urgent coronary revascularization with PCI or CABG ≥ 30 days after randomization. A Clinical Endpoints Committee (CEC) reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or who were lost to follow-up and had no event were censored at the time of last available information (last study visit). The Kaplan-Meier estimate reports the percentage of participants who experienced CHD death, non-fatal MI, or urgent coronary revascularization with PCI or CABG ≥ 30 days after randomization within 7 years from randomization.

Time frame:
Up to approximately 9 years
Reported as:
Number · Percentage of Participants
Time to First Occurrence of Coronary Heart Disease (CHD) Death, Non-fatal MI, or Urgent Coronary Revascularization With PCI or CABG ≥ 30 Days After Randomization (Kaplan-Meier Estimate of Percentage of Participants Experiencing a Qualifying Event)
Percentage of ParticipantsEzetimibe/SimvastatinSimvastatin
Time to First Occurrence of Coronary Heart Disease (CHD) Death, Non-fatal MI, or Urgent Coronary Revascularization With PCI or CABG ≥ 30 Days After Randomization (Kaplan-Meier Estimate of Percentage of Participants Experiencing a Qualifying Event)17.52 (16.62 to 18.46)18.88 (17.96 to 19.83)
Statistical analysis
  • Ezetimibe/Simvastatin vs Simvastatin · Cox proportional hazard model · p = 0.016 · Hazard ratio (hr): 0.912 · 95% CI 0.847 to 0.983Model includes events from randomization to last study visit.
SecondaryTime to First Occurrence of CV Death, Nonfatal MI, UA With Hospitalization, All Revascularization Occurring ≥30 Days After Randomization, and Non-fatal Stroke (Kaplan-Meier Estimate of Percentage of Participants Experiencing a Qualifying Event)

The time (in months) from study start to the first occurrence of any of the following clinical outcomes was recorded: CV death, non-fatal MI, documented UA that requires admission into a hospital, all revascularization (including non-coronary) occurring at least 30 days after randomization, and non-fatal stroke. A Clinical Endpoints Committee (CEC) reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or who were lost to follow-up and had no event were censored at the time of last available information (last study visit). The Kaplan-Meier estimate reports the percentage of participants who experienced CV death, non-fatal MI, unstable angina with hospitalization, all revascularization occurring ≥ 30 days after randomization, and non-fatal stroke within 7 Years from randomization.

Time frame:
Up to approximately 9 years
Reported as:
Number · Percentage of Participants
Time to First Occurrence of CV Death, Nonfatal MI, UA With Hospitalization, All Revascularization Occurring ≥30 Days After Randomization, and Non-fatal Stroke (Kaplan-Meier Estimate of Percentage of Participants Experiencing a Qualifying Event)
Percentage of ParticipantsEzetimibe/SimvastatinSimvastatin
Time to First Occurrence of CV Death, Nonfatal MI, UA With Hospitalization, All Revascularization Occurring ≥30 Days After Randomization, and Non-fatal Stroke (Kaplan-Meier Estimate of Percentage of Participants Experiencing a Qualifying Event)34.49 (33.38 to 35.63)36.20 (35.07 to 37.34)
Statistical analysis
  • Ezetimibe/Simvastatin vs Simvastatin · Cox proportional hazard model · p = 0.035 · Hazard ratio (hr): 0.945 · 95% CI 0.897 to 0.996Model includes events from randomization to last study visit.

Adverse events

Collected over up to 30 days after last dose of study drug (Up to approximately 9 years maximum). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Ezetimide/Simvastatin—3,640/9,067 (40.1%)5,486/9,067 (60.5%)
Simvastatin—3,649/9,077 (40.2%)5,472/9,077 (60.3%)
Most frequent serious events
Showing 10 of 1,812
Most frequent serious events
EventEzetimide/SimvastatinSimvastatin
PneumoniaInfections and infestations255/9067242/9077
OsteoarthritisMusculoskeletal and connective tissue disorders175/9067159/9077
Basal Cell CarcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)140/9067157/9077
Atrial FibrillationCardiac disorders140/9067150/9077
Prostate CancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)123/9067117/9077
Chronic Obstructive Pulmonary DiseaseRespiratory, thoracic and mediastinal disorders109/9067105/9077
SyncopeNervous system disorders107/906796/9077
Squamous Cell CarcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)84/906791/9077
Urinary Tract InfectionInfections and infestations77/906779/9077
CholelithiasisHepatobiliary disorders78/906771/9077
Most frequent other events
Showing 10 of 19
Most frequent other events
EventEzetimide/SimvastatinSimvastatin
ArthralgiaMusculoskeletal and connective tissue disorders1001/9067914/9077
Pain In ExtremityMusculoskeletal and connective tissue disorders955/9067899/9077
MyalgiaMusculoskeletal and connective tissue disorders954/9067908/9077
DizzinessNervous system disorders875/9067909/9077
Back PainMusculoskeletal and connective tissue disorders866/9067825/9077
DyspnoeaRespiratory, thoracic and mediastinal disorders787/9067815/9077
FatigueGeneral disorders720/9067756/9077
CoughRespiratory, thoracic and mediastinal disorders702/9067740/9077
Chest PainGeneral disorders694/9067731/9077
HypertensionVascular disorders580/9067642/9077

Baseline characteristics

Age, Continuous
Age, Continuous(years)Ezetimibe/SimvastatinSimvastatinTotal
Mean63.6 ± 9.763.6 ± 9.863.6 ± 9.8
Sex: Female, Male
Sex: Female, Male(Participants)Ezetimibe/SimvastatinSimvastatinTotal
Female222521914416
Male6842688613728
08

Study locations

No study locations are listed for this record.

09

References and documents

Publications

  • Blazing MA, Giugliano RP, Cannon CP, Musliner TA, Tershakovec AM, White JA, Reist C, McCagg A, Braunwald E, Califf RM. Evaluating cardiovascular event reduction with ezetimibe as an adjunct to simvastatin in 18,144 patients after acute coronary syndromes: final baseline characteristics of the IMPROVE-IT study population. Am Heart J. 2014 Aug;168(2):205-12.e1. doi: 10.1016/j.ahj.2014.05.004. Epub 2014 May 15. PubMed 25066560 ↗
  • Califf RM, Lokhnygina Y, Cannon CP, Stepanavage ME, McCabe CH, Musliner TA, Pasternak RC, Blazing MA, Giugliano RP, Harrington RA, Braunwald E. An update on the IMProved reduction of outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) design. Am Heart J. 2010 May;159(5):705-9. doi: 10.1016/j.ahj.2010.03.004. Epub 2010 Mar 15. No abstract available. PubMed 20435175 ↗
  • Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, Darius H, Lewis BS, Ophuis TO, Jukema JW, De Ferrari GM, Ruzyllo W, De Lucca P, Im K, Bohula EA, Reist C, Wiviott SD, Tershakovec AM, Musliner TA, Braunwald E, Califf RM; IMPROVE-IT Investigators. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015 Jun 18;372(25):2387-97. doi: 10.1056/NEJMoa1410489. Epub 2015 Jun 3. PubMed 26039521 ↗
  • Bohula EA, Giugliano RP, Cannon CP, Zhou J, Murphy SA, White JA, Tershakovec AM, Blazing MA, Braunwald E. Achievement of dual low-density lipoprotein cholesterol and high-sensitivity C-reactive protein targets more frequent with the addition of ezetimibe to simvastatin and associated with better outcomes in IMPROVE-IT. Circulation. 2015 Sep 29;132(13):1224-33. doi: 10.1161/CIRCULATIONAHA.115.018381. Epub 2015 Sep 1. PubMed 26330412 ↗
  • Cheng Y, Zhai S, Zhong W, West RM, Shen J. Improving polygenic risk score based drug response prediction using transfer learning. NPJ Genom Med. 2025 Nov 21;10(1):74. doi: 10.1038/s41525-025-00528-x. PubMed 41271821 ↗
  • Tunnicliffe DJ, Palmer SC, Cashmore BA, Saglimbene VM, Krishnasamy R, Lambert K, Johnson DW, Craig JC, Strippoli GF. HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis. Cochrane Database Syst Rev. 2023 Nov 29;11(11):CD007784. doi: 10.1002/14651858.CD007784.pub3. PubMed 38018702 ↗
  • Patel SM, Qamar A, Giugliano RP, Jarolim P, Marston NA, Park JG, Blazing MA, Cannon CP, Braunwald E, Morrow DA. Association of Serial High-Sensitivity Cardiac Troponin T With Subsequent Cardiovascular Events in Patients Stabilized After Acute Coronary Syndrome: A Secondary Analysis From IMPROVE-IT. JAMA Cardiol. 2022 Dec 1;7(12):1199-1206. doi: 10.1001/jamacardio.2022.3627. PubMed 36260325 ↗
  • Fordyce CB, Giugliano RP, Cannon CP, Roe MT, Sharma A, Page C, White JA, Lokhnygina Y, Braunwald E, Blazing MA. Cardiovascular Events and Long-Term Risk of Sudden Death Among Stabilized Patients After Acute Coronary Syndrome: Insights From IMPROVE-IT. J Am Heart Assoc. 2022 Feb 15;11(4):e022733. doi: 10.1161/JAHA.121.022733. Epub 2022 Feb 3. PubMed 35112882 ↗
  • Oyama K, Giugliano RP, Blazing MA, Park JG, Tershakovec AM, Sabatine MS, Cannon CP, Braunwald E. Baseline Low-Density Lipoprotein Cholesterol and Clinical Outcomes of Combining Ezetimibe With Statin Therapy in IMPROVE-IT. J Am Coll Cardiol. 2021 Oct 12;78(15):1499-1507. doi: 10.1016/j.jacc.2021.08.011. PubMed 34620406 ↗
  • Giugliano RP, Gencer B, Wiviott SD, Park JG, Fuchs CS, Goessling W, Musliner TA, Tershakovec AM, Blazing MA, Califf R, Cannon CP, Braunwald E. Prospective Evaluation of Malignancy in 17,708 Patients Randomized to Ezetimibe Versus Placebo: Analysis From IMPROVE-IT. JACC CardioOncol. 2020 Sep 15;2(3):385-396. doi: 10.1016/j.jaccao.2020.07.008. eCollection 2020 Sep. PubMed 34396246 ↗
  • Nanna MG, Navar AM, Giugliano RP, White JA, Lokhnygina Y, Mitchel YB, Musliner TA, Cannon CP, Blazing MA. Muscle Complaints or Events in Patients Randomized to Simvastatin or Ezetimibe/Simvastatin. J Am Coll Cardiol. 2020 Feb 25;75(7):835-837. doi: 10.1016/j.jacc.2019.12.022. No abstract available. PubMed 32081289 ↗
  • Bach RG, Cannon CP, Giugliano RP, White JA, Lokhnygina Y, Bohula EA, Califf RM, Braunwald E, Blazing MA. Effect of Simvastatin-Ezetimibe Compared With Simvastatin Monotherapy After Acute Coronary Syndrome Among Patients 75 Years or Older: A Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiol. 2019 Sep 1;4(9):846-854. doi: 10.1001/jamacardio.2019.2306. PubMed 31314050 ↗
  • Sharma A, Sun JL, Lokhnygina Y, Roe MT, Ahmad T, Desai NR, Blazing MA. Patient Phenotypes, Cardiovascular Risk, and Ezetimibe Treatment in Patients After Acute Coronary Syndromes (from IMPROVE-IT). Am J Cardiol. 2019 Apr 15;123(8):1193-1201. doi: 10.1016/j.amjcard.2019.01.034. Epub 2019 Jan 25. PubMed 30739657 ↗
  • Navar AM, Roe MT, White JA, Cannon CP, Lokhnygina Y, Newby LK, Giugliano RP, Tershakovec AM, Braunwald E, Califf RM, Blazing MA. Medication Discontinuation in the IMPROVE-IT Trial. Circ Cardiovasc Qual Outcomes. 2019 Jan;12(1):e005041. doi: 10.1161/CIRCOUTCOMES.118.005041. PubMed 30630361 ↗
  • Bonaca MP, Gutierrez JA, Cannon C, Giugliano R, Blazing M, Park JG, White J, Tershakovec A, Braunwald E. Polyvascular disease, type 2 diabetes, and long-term vascular risk: a secondary analysis of the IMPROVE-IT trial. Lancet Diabetes Endocrinol. 2018 Dec;6(12):934-943. doi: 10.1016/S2213-8587(18)30290-0. Epub 2018 Nov 2. PubMed 30396865 ↗
  • Simon TG, Corey KE, Cannon CP, Blazing M, Park JG, O'Donoghue ML, Chung RT, Giugliano RP. The nonalcoholic fatty liver disease (NAFLD) fibrosis score, cardiovascular risk stratification and a strategy for secondary prevention with ezetimibe. Int J Cardiol. 2018 Nov 1;270:245-252. doi: 10.1016/j.ijcard.2018.05.087. Epub 2018 May 26. PubMed 29903515 ↗
  • Giugliano RP, Cannon CP, Blazing MA, Nicolau JC, Corbalan R, Spinar J, Park JG, White JA, Bohula EA, Braunwald E; IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) Investigators. Benefit of Adding Ezetimibe to Statin Therapy on Cardiovascular Outcomes and Safety in Patients With Versus Without Diabetes Mellitus: Results From IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Circulation. 2018 Apr 10;137(15):1571-1582. doi: 10.1161/CIRCULATIONAHA.117.030950. Epub 2017 Dec 20. PubMed 29263150 ↗
  • Kato ET, Cannon CP, Blazing MA, Bohula E, Guneri S, White JA, Murphy SA, Park JG, Braunwald E, Giugliano RP. Efficacy and Safety of Adding Ezetimibe to Statin Therapy Among Women and Men: Insight From IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). J Am Heart Assoc. 2017 Nov 18;6(11):e006901. doi: 10.1161/JAHA.117.006901. PubMed 29151034 ↗
  • Bohula EA, Wiviott SD, Giugliano RP, Blazing MA, Park JG, Murphy SA, White JA, Mach F, Van de Werf F, Dalby AJ, White HD, Tershakovec AM, Cannon CP, Braunwald E. Prevention of Stroke with the Addition of Ezetimibe to Statin Therapy in Patients With Acute Coronary Syndrome in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Circulation. 2017 Dec 19;136(25):2440-2450. doi: 10.1161/CIRCULATIONAHA.117.029095. Epub 2017 Sep 30. PubMed 28972004 ↗
  • Pokharel Y, Chinnakondepalli K, Vilain K, Wang K, Mark DB, Davies G, Blazing MA, Giugliano RP, Braunwald E, Cannon CP, Cohen DJ, Magnuson EA. Impact of Ezetimibe on the Rate of Cardiovascular-Related Hospitalizations and Associated Costs Among Patients With a Recent Acute Coronary Syndrome: Results From the IMPROVE-IT Trial (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Circ Cardiovasc Qual Outcomes. 2017 May;10(5):e003201. doi: 10.1161/CIRCOUTCOMES.116.003201. PubMed 28506979 ↗
  • Giugliano RP, Wiviott SD, Blazing MA, De Ferrari GM, Park JG, Murphy SA, White JA, Tershakovec AM, Cannon CP, Braunwald E. Long-term Safety and Efficacy of Achieving Very Low Levels of Low-Density Lipoprotein Cholesterol : A Prespecified Analysis of the IMPROVE-IT Trial. JAMA Cardiol. 2017 May 1;2(5):547-555. doi: 10.1001/jamacardio.2017.0083. PubMed 28291866 ↗
  • Bohula EA, Morrow DA, Giugliano RP, Blazing MA, He P, Park JG, Murphy SA, White JA, Kesaniemi YA, Pedersen TR, Brady AJ, Mitchel Y, Cannon CP, Braunwald E. Atherothrombotic Risk Stratification and Ezetimibe for Secondary Prevention. J Am Coll Cardiol. 2017 Feb 28;69(8):911-921. doi: 10.1016/j.jacc.2016.11.070. PubMed 28231942 ↗
  • Murphy SA, Cannon CP, Blazing MA, Giugliano RP, White JA, Lokhnygina Y, Reist C, Im K, Bohula EA, Isaza D, Lopez-Sendon J, Dellborg M, Kher U, Tershakovec AM, Braunwald E. Reduction in Total Cardiovascular Events With Ezetimibe/Simvastatin Post-Acute Coronary Syndrome: The IMPROVE-IT Trial. J Am Coll Cardiol. 2016 Feb 2;67(4):353-361. doi: 10.1016/j.jacc.2015.10.077. PubMed 26821621 ↗
  • Azar RR, Badaoui G, Sarkis A, Azar M, Aydanian H, Harb S, Achkouty G, Kassab R. Effect of ezetimibe/atorvastatin combination on oxidized low density lipoprotein cholesterol in patients with coronary artery disease or coronary artery disease equivalent. Am J Cardiol. 2010 Jul 15;106(2):193-7. doi: 10.1016/j.amjcard.2010.03.016. PubMed 20599002 ↗
  • Cannon CP, Giugliano RP, Blazing MA, Harrington RA, Peterson JL, Sisk CM, Strony J, Musliner TA, McCabe CH, Veltri E, Braunwald E, Califf RM; IMPROVE-IT Investigators. Rationale and design of IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial): comparison of ezetimbe/simvastatin versus simvastatin monotherapy on cardiovascular outcomes in patients with acute coronary syndromes. Am Heart J. 2008 Nov;156(5):826-32. doi: 10.1016/j.ahj.2008.07.023. Epub 2008 Sep 2. PubMed 19061694 ↗
  • Peto R, Emberson J, Landray M, Baigent C, Collins R, Clare R, Califf R. Analyses of cancer data from three ezetimibe trials. N Engl J Med. 2008 Sep 25;359(13):1357-66. doi: 10.1056/NEJMsa0806603. Epub 2008 Sep 2. PubMed 18765432 ↗
  • Drazen JM, Jarcho JA, Morrissey S, Curfman GD. Cholesterol lowering and ezetimibe. N Engl J Med. 2008 Apr 3;358(14):1507-8. doi: 10.1056/NEJMe0801842. Epub 2008 Mar 30. No abstract available. PubMed 18376001 ↗

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 18, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT00202878
Lead sponsor
Organon and Co
Responsible party
Sponsor
First posted
Sep 20, 2005
Start date
Oct 17, 2005
Primary completion
Sep 18, 2014
Completion
Sep 18, 2014
Results posted
Sep 30, 2015
Last update
Jun 18, 2024

Study contacts

Medical Director
study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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