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CompletedNCT00092677Updated May 16, 2024Results posted

An Investigational Drug on Clinical Outcomes in Patients With Aortic Stenosis (Narrowing of the Major Blood Vessel of the Heart)(MK-0653A-043 AM4)(COMPLETED)

A Phase 3 interventional study of ezetimibe (+) simvastatin and Comparator: Placebo in Aortic Stenosis, sponsored by Organon and Co. Completed. Open to participants aged 45 Years to 85 Years. Per ClinicalTrials.gov, last updated 2024-05-16.

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

Phase
Phase 3
Study type
Interventional
Enrollment
1,873
Allocation
Randomized
Ages
45 Years to 85 Years
Sex
All
01

Study summary

The purpose of this study is to evaluate whether treatment with an investigational drug as compared to placebo will reduce the risk of major cardiovascular events in patients with aortic stenosis.

02

Conditions studied

  • Aortic Stenosis
03

In context

Aortic Valve Stenosis

1,006 studies on the registry are indexed under Aortic Valve Stenosis; 284 are open to participants now.

This study's enrollment of 1,873 is above the median of 120 across 537 interventional studies indexed under Aortic Valve Stenosis.

Browse Aortic Valve Stenosis 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
45 Years to 85 Years
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

  • Patients aged 45 to 85 with mild abnormalities of the aortic valve as confirmed by an echocardiogram.

Exclusion criteria

Exclusion Criteria:

  • Patients previously in a trial using the study drug, or currently taking any medications that are not allowed in this study.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
1,873 participants (actual)

Study arms

  • Experimental
    EZ/Simva 10/40 mg

    Ezetimibe 10 mg + Simvastatin 40 mg

    Drug: ezetimibe (+) simvastatin

  • Placebo comparator
    Placebo

    Drug: Comparator: Placebo

Interventions

  • Drugezetimibe (+) simvastatin

    Drug pages: Ezetimibe · Simvastatin

    Duration of Treatment: 4 years

    Also known as: MK0653A

  • DrugComparator: Placebo

    matching Placebo

06

What researchers measure

Primary outcomes

  1. Number of Participants That Experienced One or More Components of the Composite Clinical Endpoint of MCE (Major Cardiovascular Events)

    Composite endpoint of MCE consists of cardiovascular death, AVR (aortic valve replacement) surgery, CHF(congestive heart failure) as a result of progression of aortic stenosis, nonfatal MI (myocardial infarction), CABG (coronary artery bypass) surgery, PCI (percutaneous coronary intervention), hospitalized unstable angina, and nonhemorrhagic stroke

    Time frame: Entire follow-up (median = 4.35 years)

Secondary outcomes

  1. Number of Participants That Experienced One or More Components of the Composite Clinical Endpoint of AVE (Aortic Valve Events)

    Composite endpoint of AVE (aortic valve events) consists of AVR surgery, CHF (as a result of progression of AS), or cardiovascular death

    Time frame: Entire follow-up (median = 4.35 years)

  2. Number of Participants That Experienced One or More Components of the Composite Clinical Endpoint of ICE (Ischemic Cardiovascular Events)

    Composite endpoint of ICE (ischemic cardiovascular events) consists of cardiovascular death, nonfatal MI, CABG, PCI, hospitalized unstable angina, and nonhemorrhagic stroke

    Time frame: Entire follow-up (median = 4.35 years)

  3. Change From Baseline in Peak Transaortic Jet Velocity

    Mean change from baseline in peak transaortic jet velocity

    Time frame: Baseline to End of follow-up (median = 4.35 years) or pre-aortic valve replacement

Other outcomes

  1. Cardiovascular Death

    Number of participants that experienced cardiovascular death

    Time frame: Entire follow-up (median = 4.35 years)

  2. Aortic Valve Replacement (AVR)

    Number of participants that experienced aortic valve replacement (AVR)

    Time frame: Entire follow-up (median = 4.35 years)

  3. Congestive Heart Failure (CHF) Due to Progression of Aortic Stenosis (AS)

    Number of participants that experienced Congestive Heart Failure (CHF) due to progression of aortic stenosis (AS)

    Time frame: Entire follow-up (median = 4.35 years)

  4. Nonfatal Myocardial Infarction (MI)

    Number of participants that experienced nonfatal myocardial infarction (MI)

    Time frame: Entire follow-up (median = 4.35 years)

  5. Coronary Artery Bypass Grafting (CABG)

    Number of participants that experienced coronary artery bypass grafting (CABG)

    Time frame: Entire follow-up (median = 4.35 years)

  6. Percutaneous Coronary Intervention (PCI)

    Number of participants that experienced percutaneous coronary intervention (PCI)

    Time frame: Entire follow-up (median = 4.35 years)

  7. Hospitalization for Unstable Angina

    Number of participants that experienced hospitalization for unstable angina

    Time frame: Entire follow-up (median = 4.35 years)

  8. Nonhemorrhagic Stroke

    Number of participants that experienced nonhemorrhagic stroke

    Time frame: Entire follow-up (median = 4.35 years)

  9. Death (Any Cause)

    Number of participants that died (any cause)

    Time frame: Entire follow-up (median = 4.35 years)

  10. Percent Change in Time Weighted Average Total Cholesterol From Baseline to End of Follow-up

    Mean percent change (time-weighted average over follow-up) from baseline: Time-weighted average calculated using values at week 8, week 24, year 1 and every 6 months with time interval (days) between 2 successive values used as the weighting factor. For the first follow-up value, the weight was the number of days from randomization.

    Time frame: Baseline to End of follow-up (median = 4.35 years)

  11. Percent Change in Time Weighted Average Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to End of Follow-up

    Mean percent change (time-weighted average over follow-up) from baseline: Time-weighted average calculated using values at week 8, week 24, year 1 and every 6 months with time interval (days) between 2 successive values used as the weighting factor. For the first follow-up value, the weight was the number of days from randomization.

    Time frame: Baseline to End of follow-up (median = 4.35 years)

  12. Percent Change in Time Weighted Average High-density Lipoprotein Cholesterol (HDL-C) From Baseline to End of Follow-up

    Mean percent change (time-weighted average over follow-up) from baseline: Time-weighted average calculated using values at week 8, week 24, year 1 and every 6 months with time interval (days) between 2 successive values used as the weighting factor. For the first follow-up value, the weight was the number of days from randomization.

    Time frame: Baseline to End of follow-up (median = 4.35 years)

  13. Percent Change in Time Weighted Average Triglycerides From Baseline to End of Follow-up

    Mean percent change (time-weighted average over follow-up) from baseline: Time-weighted average calculated using values at week 8, week 24, year 1 and every 6 months with time interval (days) between 2 successive values used as the weighting factor. For the first follow-up value, the weight was the number of days from randomization.

    Time frame: Baseline to End of follow-up (median = 4.35 years)

07

Results

Posted May 27, 2009
Limitations and caveats
It is important to note that several of the ischemic outcomes making up the composite ischemic endpoint can occur as a causal consequence of aortic stenosis progression itself, or in association with its standard treatment (aortic valve replacement).

Participant flow

Phase III. Study Initiation Date (FPI) was 06-Jan-2003 and Study Completion Date (LPO) was 17-Apr-2008. Primary therapy period 02-Mar-2001 to 31-Mar-2008 includes start date of therapy from the Simvastatin in Aortic Stenosis (SAS) study. 173 study centers worldwide (Denmark, Finland, Germany, Great Britain, Ireland, Norway, and Sweden)

Participant flow — Overall Study
MilestoneEZ/Simva 10/40 mgPlacebo
Started944929
Completed939918
Not completed511
Withdrew: Lost to follow-up02
Withdrew: Adminstrative59

Outcome measures

PrimaryNumber of Participants That Experienced One or More Components of the Composite Clinical Endpoint of MCE (Major Cardiovascular Events)

Composite endpoint of MCE consists of cardiovascular death, AVR (aortic valve replacement) surgery, CHF(congestive heart failure) as a result of progression of aortic stenosis, nonfatal MI (myocardial infarction), CABG (coronary artery bypass) surgery, PCI (percutaneous coronary intervention), hospitalized unstable angina, and nonhemorrhagic stroke

Time frame:
Entire follow-up (median = 4.35 years)
Reported as:
Number · Participants
Number of Participants That Experienced One or More Components of the Composite Clinical Endpoint of MCE (Major Cardiovascular Events)
ParticipantsEZ/Simva 10/40 mgPlacebo
Number of Participants That Experienced One or More Components of the Composite Clinical Endpoint of MCE (Major Cardiovascular Events)333355
Statistical analysis
  • EZ/Simva 10/40 mg vs Placebo · Regression, Cox · p = 0.591 · Hazard ratio (hr): 0.960 · 95% CI 0.826 to 1.115Direction of the Comparison: Hazard Ratio of experiencing the endpoint on EZ/Simva 10/40 mg compared to Placebo
SecondaryNumber of Participants That Experienced One or More Components of the Composite Clinical Endpoint of AVE (Aortic Valve Events)

Composite endpoint of AVE (aortic valve events) consists of AVR surgery, CHF (as a result of progression of AS), or cardiovascular death

Time frame:
Entire follow-up (median = 4.35 years)
Reported as:
Number · Participants
Number of Participants That Experienced One or More Components of the Composite Clinical Endpoint of AVE (Aortic Valve Events)
ParticipantsEZ/Simva 10/40 mgPlacebo
Number of Participants That Experienced One or More Components of the Composite Clinical Endpoint of AVE (Aortic Valve Events)308326
Statistical analysis
  • EZ/Simva 10/40 mg vs Placebo · Regression, Cox · p = 0.732 · Hazard ratio (hr): 0.973 · 95% CI 0.833 to 1.137Direction of the Comparison: Hazard Ratio of experiencing the endpoint on EZ/Simva 10/40 mg compared to Placebo
SecondaryNumber of Participants That Experienced One or More Components of the Composite Clinical Endpoint of ICE (Ischemic Cardiovascular Events)

Composite endpoint of ICE (ischemic cardiovascular events) consists of cardiovascular death, nonfatal MI, CABG, PCI, hospitalized unstable angina, and nonhemorrhagic stroke

Time frame:
Entire follow-up (median = 4.35 years)
Reported as:
Number · Participants
Number of Participants That Experienced One or More Components of the Composite Clinical Endpoint of ICE (Ischemic Cardiovascular Events)
ParticipantsEZ/Simva 10/40 mgPlacebo
Number of Participants That Experienced One or More Components of the Composite Clinical Endpoint of ICE (Ischemic Cardiovascular Events)148187
Statistical analysis
  • EZ/Simva 10/40 mg vs Placebo · Regression, Cox · p = 0.024 · Hazard ratio (hr): 0.780 · 95% CI 0.628 to 0.967Direction of the Comparison: Hazard Ratio of experiencing the endpoint on EZ/Simva 10/40 mg compared to Placebo
Other pre-specifiedCardiovascular Death

Number of participants that experienced cardiovascular death

Time frame:
Entire follow-up (median = 4.35 years)
Reported as:
Number · Participants
Cardiovascular Death
ParticipantsEZ/Simva 10/40 mgPlacebo
Cardiovascular Death4756
Statistical analysis
  • EZ/Simva 10/40 mg vs Placebo · Regression, Cox · p = 0.344 · Hazard ratio (hr): 0.829 · 95% CI 0.563 to 1.222Direction of the Comparison: Hazard Ratio of experiencing the endpoint on EZ/Simva 10/40 mg compared to Placebo
Other pre-specifiedAortic Valve Replacement (AVR)

Number of participants that experienced aortic valve replacement (AVR)

Time frame:
Entire follow-up (median = 4.35 years)
Reported as:
Number · Participants
Aortic Valve Replacement (AVR)
ParticipantsEZ/Simva 10/40 mgPlacebo
Aortic Valve Replacement (AVR)267278
Statistical analysis
  • EZ/Simva 10/40 mg vs Placebo · Regression, Cox · p = 0.968 · Hazard ratio (hr): 0.997 · 95% CI 0.842 to 1.179Direction of the Comparison: Hazard Ratio of experiencing the endpoint on EZ/Simva 10/40 mg compared to Placebo
Other pre-specifiedCongestive Heart Failure (CHF) Due to Progression of Aortic Stenosis (AS)

Number of participants that experienced Congestive Heart Failure (CHF) due to progression of aortic stenosis (AS)

Time frame:
Entire follow-up (median = 4.35 years)
Reported as:
Number · Participants
Congestive Heart Failure (CHF) Due to Progression of Aortic Stenosis (AS)
ParticipantsEZ/Simva 10/40 mgPlacebo
Congestive Heart Failure (CHF) Due to Progression of Aortic Stenosis (AS)2523
Statistical analysis
  • EZ/Simva 10/40 mg vs Placebo · Regression, Cox · p = 0.771 · Hazard ratio (hr): 1.088 · 95% CI 0.617 to 1.917Direction of the Comparison: Hazard Ratio of experiencing the endpoint on EZ/Simva 10/40 mg compared to Placebo
Other pre-specifiedNonfatal Myocardial Infarction (MI)

Number of participants that experienced nonfatal myocardial infarction (MI)

Time frame:
Entire follow-up (median = 4.35 years)
Reported as:
Number · Participants
Nonfatal Myocardial Infarction (MI)
ParticipantsEZ/Simva 10/40 mgPlacebo
Nonfatal Myocardial Infarction (MI)1726
Statistical analysis
  • EZ/Simva 10/40 mg vs Placebo · Regression, Cox · p = 0.147 · Hazard ratio (hr): 0.636 · 95% CI 0.345 to 1.173Direction of the Comparison: Hazard Ratio of experiencing the endpoint on EZ/Simva 10/40 mg compared to Placebo
Other pre-specifiedCoronary Artery Bypass Grafting (CABG)

Number of participants that experienced coronary artery bypass grafting (CABG)

Time frame:
Entire follow-up (median = 4.35 years)
Reported as:
Number · Participants
Coronary Artery Bypass Grafting (CABG)
ParticipantsEZ/Simva 10/40 mgPlacebo
Coronary Artery Bypass Grafting (CABG)69100
Statistical analysis
  • EZ/Simva 10/40 mg vs Placebo · Regression, Cox · p = 0.015 · Hazard ratio (hr): 0.683 · 95% CI 0.503 to 0.929Direction of the Comparison: Hazard Ratio of experiencing the endpoint on EZ/Simva 10/40 mg compared to Placebo
Other pre-specifiedPercutaneous Coronary Intervention (PCI)

Number of participants that experienced percutaneous coronary intervention (PCI)

Time frame:
Entire follow-up (median = 4.35 years)
Reported as:
Number · Participants
Percutaneous Coronary Intervention (PCI)
ParticipantsEZ/Simva 10/40 mgPlacebo
Percutaneous Coronary Intervention (PCI)817
Statistical analysis
  • EZ/Simva 10/40 mg vs Placebo · Regression, Cox · Hazard ratio (hr): 0.456 · 95% CI 0.197 to 1.057Direction of the Comparison: Hazard Ratio of experiencing the endpoint on EZ/Simva 10/40 mg compared to Placebo
Other pre-specifiedHospitalization for Unstable Angina

Number of participants that experienced hospitalization for unstable angina

Time frame:
Entire follow-up (median = 4.35 years)
Reported as:
Number · Participants
Hospitalization for Unstable Angina
ParticipantsEZ/Simva 10/40 mgPlacebo
Hospitalization for Unstable Angina58
Statistical analysis
  • EZ/Simva 10/40 mg vs Placebo · Regression, Cox · Hazard ratio (hr): 0.608 · 95% CI 0.199 to 1.860Direction of the Comparison: Hazard Ratio of experiencing the endpoint on EZ/Simva 10/40 mg compared to Placebo
Other pre-specifiedNonhemorrhagic Stroke

Number of participants that experienced nonhemorrhagic stroke

Time frame:
Entire follow-up (median = 4.35 years)
Reported as:
Number · Participants
Nonhemorrhagic Stroke
ParticipantsEZ/Simva 10/40 mgPlacebo
Nonhemorrhagic Stroke3329
Statistical analysis
  • EZ/Simva 10/40 mg vs Placebo · Regression, Cox · p = 0.647 · Hazard ratio (hr): 1.124 · 95% CI 0.682 to 1.850Direction of the Comparison: Hazard Ratio of experiencing the endpoint on EZ/Simva 10/40 mg compared to Placebo
Other pre-specifiedDeath (Any Cause)

Number of participants that died (any cause)

Time frame:
Entire follow-up (median = 4.35 years)
Reported as:
Number · Participants
Death (Any Cause)
ParticipantsEZ/Simva 10/40 mgPlacebo
Death (Any Cause)105100
Statistical analysis
  • EZ/Simva 10/40 mg vs Placebo · Regression, Cox · p = 0.799 · Hazard ratio (hr): 1.036 · 95% CI 0.788 to 1.363Direction of the Comparison: Hazard Ratio of experiencing the endpoint on EZ/Simva 10/40 mg compared to Placebo
Post-hocDeath Due to Cancer

Number of participants that died due to cancer

Time frame:
Entire follow-up (median = 4.35 years)
Reported as:
Number · Participants
Death Due to Cancer
ParticipantsEZ/Simva 10/40 mgPlacebo
Death Due to Cancer3923
Statistical analysis
  • EZ/Simva 10/40 mg vs Placebo · Regression, Cox · p = 0.052 · Hazard ratio (hr): 1.667 · 95% CI 0.996 to 2.791Direction of the Comparison: Hazard Ratio of experiencing the endpoint on EZ/Simva 10/40 mg compared to Placebo
Post-hocIncident Cancer

Number of participants with incident cancer

Time frame:
Entire follow-up (median = 4.35 years)
Reported as:
Number · Participants
Incident Cancer
ParticipantsEZ/Simva 10/40 mgPlacebo
Incident Cancer10570
Statistical analysis
  • EZ/Simva 10/40 mg vs Placebo · Regression, Cox · p = 0.008 · Hazard ratio (hr): 1.504 · 95% CI 1.111 to 2.035Direction of the Comparison: Hazard Ratio of experiencing the endpoint on EZ/Simva 10/40 mg compared to Placebo
SecondaryChange From Baseline in Peak Transaortic Jet Velocity

Mean change from baseline in peak transaortic jet velocity

Time frame:
Baseline to End of follow-up (median = 4.35 years) or pre-aortic valve replacement
Reported as:
Mean · m/sec
Change From Baseline in Peak Transaortic Jet Velocity
m/secEZ/Simva 10/40 mgPlacebo
Change From Baseline in Peak Transaortic Jet Velocity0.613 ± 0.5860.618 ± 0.612
Statistical analysis
  • EZ/Simva 10/40 mg vs Placebo · ANCOVA · p = 0.829 · Mean difference (final values): -0.006 · 95% CI -0.063 to 0.051Direction of the Comparison: EZ/Simva 10/40 mg minus Placebo
Other pre-specifiedPercent Change in Time Weighted Average Total Cholesterol From Baseline to End of Follow-up

Mean percent change (time-weighted average over follow-up) from baseline: Time-weighted average calculated using values at week 8, week 24, year 1 and every 6 months with time interval (days) between 2 successive values used as the weighting factor. For the first follow-up value, the weight was the number of days from randomization.

Time frame:
Baseline to End of follow-up (median = 4.35 years)
Reported as:
Mean · Percent Change
Percent Change in Time Weighted Average Total Cholesterol From Baseline to End of Follow-up
Percent ChangeEZ/Simva 10/40 mgPlacebo
Percent Change in Time Weighted Average Total Cholesterol From Baseline to End of Follow-up-34.8 ± 13.5-2.7 ± 11.8
Statistical analysis
  • EZ/Simva 10/40 mg vs Placebo · ANOVA · p = <=0.001 · Mean difference (final values): -32.1 · 95% CI -33.3 to -31.0Direction of the Comparison: EZ/Simva 10/40 mg minus Placebo
Other pre-specifiedPercent Change in Time Weighted Average Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to End of Follow-up

Mean percent change (time-weighted average over follow-up) from baseline: Time-weighted average calculated using values at week 8, week 24, year 1 and every 6 months with time interval (days) between 2 successive values used as the weighting factor. For the first follow-up value, the weight was the number of days from randomization.

Time frame:
Baseline to End of follow-up (median = 4.35 years)
Reported as:
Mean · Percent Change
Percent Change in Time Weighted Average Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to End of Follow-up
Percent ChangeEZ/Simva 10/40 mgPlacebo
Percent Change in Time Weighted Average Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to End of Follow-up-53.8 ± 18.7-3.8 ± 20.6
Statistical analysis
  • EZ/Simva 10/40 mg vs Placebo · ANOVA · p = <=0.001 · Mean difference (final values): -50.0 · 95% CI -51.8 to -48.2Direction of the Comparison: EZ/Simva 10/40 mg minus Placebo
Other pre-specifiedPercent Change in Time Weighted Average High-density Lipoprotein Cholesterol (HDL-C) From Baseline to End of Follow-up

Mean percent change (time-weighted average over follow-up) from baseline: Time-weighted average calculated using values at week 8, week 24, year 1 and every 6 months with time interval (days) between 2 successive values used as the weighting factor. For the first follow-up value, the weight was the number of days from randomization.

Time frame:
Baseline to End of follow-up (median = 4.35 years)
Reported as:
Mean · Percent change
Percent Change in Time Weighted Average High-density Lipoprotein Cholesterol (HDL-C) From Baseline to End of Follow-up
Percent changeEZ/Simva 10/40 mgPlacebo
Percent Change in Time Weighted Average High-density Lipoprotein Cholesterol (HDL-C) From Baseline to End of Follow-up6.5 ± 17.72.5 ± 16.1
Statistical analysis
  • EZ/Simva 10/40 mg vs Placebo · ANOVA · p = <=0.001 · Mean difference (final values): 3.9 · 95% CI 2.4 to 5.5Direction of the Comparison: EZ/Simva 10/40 mg minus Placebo
Other pre-specifiedPercent Change in Time Weighted Average Triglycerides From Baseline to End of Follow-up

Mean percent change (time-weighted average over follow-up) from baseline: Time-weighted average calculated using values at week 8, week 24, year 1 and every 6 months with time interval (days) between 2 successive values used as the weighting factor. For the first follow-up value, the weight was the number of days from randomization.

Time frame:
Baseline to End of follow-up (median = 4.35 years)
Reported as:
Mean · Percent Change
Percent Change in Time Weighted Average Triglycerides From Baseline to End of Follow-up
Percent ChangeEZ/Simva 10/40 mgPlacebo
Percent Change in Time Weighted Average Triglycerides From Baseline to End of Follow-up-14.9 ± 27.65.1 ± 30.4
Statistical analysis
  • EZ/Simva 10/40 mg vs Placebo · ANOVA · p = <=0.001 · Mean difference (final values): -20.0 · 95% CI -22.6 to -17.3Direction of the Comparison: EZ/Simva 10/40 mg minus Placebo

Adverse events

Non-serious events are listed at a 2% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
EZ/Simva 10/40 mg———
Placebo———
Most frequent serious events
Showing 10 of 562
Most frequent serious events
EventEZ/Simva 10/40 mgPlacebo
Aortic valve stenosisCardiac disorders69/94360/929
Atrial fibrillationCardiac disorders45/94327/929
PneumoniaInfections and infestations28/94331/929
OsteoarthritisMusculoskeletal and connective tissue disorders19/94321/929
Chest painGeneral disorders21/94315/929
Prostate cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)21/94314/929
SyncopeNervous system disorders14/94319/929
Inguinal herniaGastrointestinal disorders15/94315/929
Urinary tract infectionInfections and infestations10/94313/929
DyspnoeaRespiratory, thoracic and mediastinal disorders12/94312/929
Most frequent other events
Showing 10 of 53
Most frequent other events
EventEZ/Simva 10/40 mgPlacebo
Aortic valve stenosisCardiac disorders139/943177/929
HypertensionVascular disorders133/943148/929
DyspnoeaRespiratory, thoracic and mediastinal disorders81/943116/929
Atrial fibrillationCardiac disorders88/943113/929
DizzinessNervous system disorders73/94377/929
ArthralgiaMusculoskeletal and connective tissue disorders61/94345/929
Oedema peripheralGeneral disorders59/94351/929
NasopharyngitisInfections and infestations57/94355/929
Back painMusculoskeletal and connective tissue disorders56/94348/929
Chest painGeneral disorders45/94352/929

Baseline characteristics

Age, Continuous
Age, Continuous(years)EZ/Simva 10/40 mgPlaceboTotal
Mean67.7 (41 to 86)67.4 (28 to 85)67.5 (28 to 86)
Sex: Female, Male
Sex: Female, Male(Participants)EZ/Simva 10/40 mgPlaceboTotal
Female363360723
Male5815691150
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)EZ/Simva 10/40 mgPlaceboTotal
White9409281868
Asian314
Other101
High-density Lipoprotein Cholesterol (HDL-C)
High-density Lipoprotein Cholesterol (HDL-C)(mmol/L)EZ/Simva 10/40 mgPlaceboTotal
Mean1.49 ± 0.431.49 ± 0.431.49 ± 0.43
Low-density Lipoprotein Cholesterol (LDL-C)
Low-density Lipoprotein Cholesterol (LDL-C)(mmol/L)EZ/Simva 10/40 mgPlaceboTotal
Mean3.62 ± 0.933.59 ± 0.913.60 ± 0.92
Peak Transaortic Jet Velocity
Peak Transaortic Jet Velocity(m/sec)EZ/Simva 10/40 mgPlaceboTotal
Mean3.09 ± 0.553.10 ± 0.543.09 ± 0.54
Total Cholesterol
Total Cholesterol(mmol/L)EZ/Simva 10/40 mgPlaceboTotal
Mean5.76 ± 1.045.73 ± 0.995.74 ± 1.02
Triglycerides (TG)
Triglycerides (TG)(mmol/L)EZ/Simva 10/40 mgPlaceboTotal
Mean1.42 ± 0.711.42 ± 0.681.42 ± 0.69
08

Study locations

No study locations are listed for this record.

09

References and documents

Publications

  • Rossebo AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, Gerdts E, Gohlke-Barwolf C, Holme I, Kesaniemi YA, Malbecq W, Nienaber CA, Ray S, Skjaerpe T, Wachtell K, Willenheimer R; SEAS Investigators. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med. 2008 Sep 25;359(13):1343-56. doi: 10.1056/NEJMoa0804602. Epub 2008 Sep 2. PubMed 18765433 ↗
  • Steine K, Rossebo AB, Stugaard M, Pedersen TR. Left ventricular systolic and diastolic function in asymptomatic patients with moderate aortic stenosis. Am J Cardiol. 2008 Oct 1;102(7):897-901. doi: 10.1016/j.amjcard.2008.07.001. Epub 2008 Aug 26. PubMed 18805118 ↗
  • Bahlmann E, Gerdts E, Einarsen E, Midtbo H, Pedersen ER, Rossebo A, Willems S, Cramariuc D. Impact of sex-specific thresholds for low flow in assessment of prognosis in concordantly and discordantly graded aortic valve stenosis. Eur Heart J Cardiovasc Imaging. 2025 Jan 31;26(2):280-286. doi: 10.1093/ehjci/jeae272. PubMed 39467305 ↗
  • Hadziselimovic E, Greve AM, Sajadieh A, Olsen MH, Kesaniemi YA, Nienaber CA, Ray SG, Rossebo AB, Wachtell K, Nielsen OW. Association of high-sensitivity troponin T with outcomes in asymptomatic non-severe aortic stenosis: a post-hoc substudy of the SEAS trial. EClinicalMedicine. 2023 Feb 28;58:101875. doi: 10.1016/j.eclinm.2023.101875. eCollection 2023 Apr. PubMed 36915288 ↗
  • Bahlmann E, Einarsen E, Cramariuc D, Pedersen ER, Rossebo AB, Midtbo H, Willems S, Gerdts E. Prognosis in asymptomatic patients with discordantly graded aortic valve stenosis based on pressure recovery adjusted valve area. Open Heart. 2022 Nov;9(2):e002159. doi: 10.1136/openhrt-2022-002159. PubMed 36428084 ↗
  • Hadziselimovic E, Greve AM, Sajadieh A, Olsen MH, Kesaniemi YA, Nienaber CA, Ray SG, Rossebo AB, Willenheimer R, Wachtell K, Nielsen OW. Association of Annual N-Terminal Pro-Brain Natriuretic Peptide Measurements With Clinical Events in Patients With Asymptomatic Nonsevere Aortic Stenosis: A Post Hoc Substudy of the SEAS Trial. JAMA Cardiol. 2022 Apr 1;7(4):435-444. doi: 10.1001/jamacardio.2021.5916. PubMed 35171199 ↗
  • Bahlmann E, Einarsen E, Cramariuc D, Midtbo H, Mancusi C, Rossebo A, Willems S, Gerdts E. Low myocardial energetic efficiency is associated with increased mortality in aortic stenosis. Open Heart. 2021 Aug;8(2):e001720. doi: 10.1136/openhrt-2021-001720. PubMed 34426527 ↗
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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 May 16, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00092677
Lead sponsor
Organon and Co
Responsible party
Sponsor
First posted
Sep 28, 2004
Start date
Jan 2001
Primary completion
Apr 2008
Completion
Apr 2008
Results posted
May 27, 2009
Last update
May 16, 2024

Study contacts

Medical Monitor
study director · Merck Sharp & Dohme LLC
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Studies of the drugs tested here: Ezetimibe · Simvastatin

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