This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Effect of Ezetimibe Treatment on Low-density Lipoprotein Cholesterol (LDL-C) Levels in Participants With Coronary Heart Disease (CHD) Already Treated With a Statin (MK-0653A-205 AM1) (NCT01381679), a registered phase not stated study. The primary outcome is Number of Participants Achieving Individual LDL Cholesterol (LDL-C) Target Level.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01381679 |
| Phase | Phase not stated |
| Condition | Hypercholesterolemia |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 1682 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Organon and Co |
| Results posted | Yes |
2. Clinical Question
Population
Participants with coronary heart disease, or a coronary heart disease equivalent, whose LDL-C targets had not been achieved while treated with a statin and for whom ezetimibe therapy was chosen.
Intervention
Ezetimibe, as an extension of existing statin therapy in routine medical care.
Comparator
No randomized or like-for-like control group is reported. The registry record says allocation was not stated and cautions that the arms are not a control comparison.
Primary question
How many participants achieved the LDL-C target assigned according to Austrian Cholesterol Consensus 2007 risk categories during follow-up of up to 12 months?
The clinical question concerns target attainment after ezetimibe was selected for participants whose LDL-C reduction with a statin had been inadequate. This is a question about the course of care in the recorded population, rather than a randomized comparison of ezetimibe against another treatment or against no treatment. The registry record describes the study as non-interventional and longitudinal, and identifies the setting as office-based routine medical care.
The target was not the same for every participant. The description states that participants were categorized as high-risk or very high-risk under the Austrian Cholesterol Consensus 2007 criteria. The corresponding LDL-C targets were 100 mg/dL and 70 mg/dL, respectively. The primary outcome therefore counts attainment of each participant’s assigned target, rather than applying a single LDL-C threshold to the entire population.
The registry record does not report the number of participants who achieved their target or the analysis supporting that outcome. It also does not report a treatment-effect estimate comparing ezetimibe with a control condition. Consequently, the clinical question can be described from the record, but the posted results do not establish how often target attainment occurred or what would have happened under an alternative treatment strategy.
3. Trial Design
The registry record describes Austrian Cholesterol Screening And Treatment II (ACT II) as a non-interventional longitudinal follow-up of the Austrian Cholesterol Screening and Treatment project (ACT I). The study concerns participants with coronary heart disease already treated with a statin. Participants whose LDL-C reduction was considered inadequate underwent an extension of therapy with ezetimibe, with target attainment as the stated goal. The recorded intervention is ezetimibe, and the arm description concerns participants for whom ezetimibe had been chosen after LDL-C targets were not achieved.
The registry record lists enrollment as 1682 and identifies hypercholesterolemia as the condition. The study status is completed; the recorded start is 2009-05 and primary completion is 2010-12. These administrative details describe the registry entry and do not, by themselves, provide outcome evidence.
This design does not establish a randomized treatment comparison. The registry record says allocation was not stated and explicitly notes that the arms are not a like-for-like control comparison. It does not identify a control group suitable for estimating what would have occurred without ezetimibe or under another treatment. Treatment was chosen in routine care, so the record describes follow-up after that choice rather than a controlled assignment.
The primary outcome was the number of participants achieving their individual LDL-C target, with a timeframe of up to 12 months. The target definitions were tied to risk category under the Austrian Cholesterol Consensus 2007. Secondary outcomes listed changes from baseline in total cholesterol, LDL-C, HDL-C, and triglycerides at Month 3 and Month 12. The registry record names these measures but does not provide their numerical results in the information available for this analysis.
The registry record does not report a detailed protocol, a recruitment procedure, the method used to determine inadequate LDL-C reduction, or the analysis population. It also does not report a statistical analysis plan. These omissions limit what can be said about how observations were selected, handled, and analyzed. A completed status indicates that the study is recorded as completed, not that its outcome estimates are available in the registry entry.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | All Participants |
|---|---|
| STARTED | 1682 |
| COMPLETED | 794 |
| NOT COMPLETED | 888 |
Reasons for not completing this period:
| Reason | All Participants |
|---|---|
| Adverse Event | 3 |
| Lost to Follow-up | 885 |
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | All Participants |
|---|---|---|
| Participants analysed | 1682 | |
| Age, Continuous | years | 64.58 (SD 10.4) |
| Sex/Gender, Customized: Males | Participants | 1003 |
| Sex/Gender, Customized: Females | Participants | 655 |
| Sex/Gender, Customized: Not Reported | Participants | 24 |
| Region of Enrollment: Austria | participants | 1682 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants Achieving Individual LDL Cholesterol (LDL-C) Target Level, measured over Up to 12 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants achieving their individual LDL-C target during follow-up of up to 12 months. It is a count outcome: the registry record describes participants as categorized according to whether they achieved the target assigned to them. The target depended on the risk category defined by the Austrian Cholesterol Consensus 2007. The listed thresholds are 100 mg/dL for high-risk participants and 70 mg/dL for very high-risk participants.
An individualized target is used because the registry record defines different LDL-C goals for different risk categories. Counting target attainment can describe whether participants reached the goal considered applicable to their category in routine care. It is distinct from measuring the mean change in LDL-C: a change from baseline describes movement in the biomarker, whereas target attainment records whether a threshold was met. A participant’s change and target status are related concepts, but one cannot be inferred from the other without the relevant individual measurements and baseline values.
The endpoint is clinically interpretable as a measure of goal attainment, but its meaning depends on the target definitions and on how target status was ascertained. The registry record gives the target categories and thresholds, but does not report the result count, the analysis method, or details about missing measurements and classification. The primary outcome result is therefore not reported in the registry record. Without that result, the endpoint definition alone does not show how many participants reached their assigned target.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record provides a description of the study question and outcome definitions, but does not report the numerical primary outcome result. It names the primary endpoint as the number of participants achieving individual LDL-C target levels through up to 12 months. It does not give the number achieving a target, an uncertainty interval, or an analysis comparing outcomes under different treatment strategies. As a result, no conclusion about the observed frequency of target attainment can be drawn from the recorded outcome information.
The design matters for interpretation. This was a non-interventional longitudinal study, not a randomized comparison. Participants received ezetimibe after it had been chosen in routine medical care because LDL-C targets had not been achieved with a statin. The registry record says allocation was not stated and warns that the arms are not a like-for-like control comparison. A change observed during follow-up could reflect the treatment course, other aspects of care, the participants’ clinical characteristics, measurement variation, or other influences. The record does not permit those possibilities to be separated by a controlled contrast.
The primary outcome uses risk-specific targets: 100 mg/dL for high-risk participants and 70 mg/dL for very high-risk participants. This makes the endpoint a measure of reaching an assigned threshold, rather than a uniform LDL-C target for all participants. It also means that a target-attainment count would need to be interpreted alongside the risk-category definitions and the process used to assign categories. The registry record does not report the distribution of participants across those categories or the outcome count within either category.
The secondary outcome list identifies changes from baseline in total cholesterol, LDL-C, HDL-C, and triglycerides at Month 3 and Month 12. Listing an outcome is not the same as reporting an estimate. Numerical results, uncertainty measures, and methods for those outcomes are not reported in the registry record. Therefore, the outcome list establishes what the study intended to track, but not what the observed changes were or how precisely they were estimated.
The enrollment entry of 1682 describes the recorded study enrollment; it does not establish how many participants contributed data to each endpoint. The registry record does not report analysis populations, missing-data handling, or outcome-specific denominators. Those details are important because follow-up measures may be unavailable for some participants, and the population contributing to an endpoint may differ from the enrollment entry.
Overall, the record supports a description of a routine-care follow-up question and its target definitions. It does not support a numerical estimate of target attainment, a treatment-effect estimate, or a causal claim about ezetimibe. No reported analysis should be inferred from the outcome titles alone.
9. Statistical Methods Explained
Statistical methods determine how recorded measurements are converted into estimates and how much uncertainty accompanies those estimates. The registry record identifies outcome measures and study features, but does not report a statistical analysis plan or numerical outcome analyses. The concepts below explain how such methods are generally understood; they do not describe methods as having been used in this study unless the registry record says so.
What does the primary count represent?
The primary outcome is a count of participants who achieved their individual LDL-C target. A count describes the number of recorded participants meeting an outcome definition. To interpret a count as a rate or proportion, the denominator must also be known: that is, the number of participants whose target status was assessed under the stated analysis rules. The registry record provides enrollment as 1682, but does not report the primary outcome count or its analysis denominator. Enrollment alone should not be substituted for an outcome-specific denominator.
The outcome definition uses targets based on risk category. The stated thresholds are 100 mg/dL for high-risk participants and 70 mg/dL for very high-risk participants. If a proportion were reported, its interpretation would depend on the target assignment and the participants included in the denominator. The record does not give the category counts or explain how missing target assessments were treated, so those features cannot be reconstructed.
What does longitudinal follow-up add?
Longitudinal data follow participants over time. They can describe how measurements change during follow-up and whether a threshold is reached. The registry record identifies follow-up through up to 12 months and lists secondary changes from baseline at Month 3 and Month 12. In general, change from baseline requires a baseline measurement and a later measurement. An analysis may use paired observations from the same participant or a model that accommodates repeated observations; the registry record does not state which approach was used.
Repeated measurements on a participant are related rather than independent. In general, statistical methods should account for that relationship when estimating changes across time. Treating related observations as independent can misstate uncertainty. The exact modeling approach, covariates, and assumptions are not reported in the registry record, so no particular repeated-measures method should be attributed to this study.
How should uncertainty be understood?
In general, a confidence interval expresses the range of estimates compatible with the observed data under a stated statistical procedure. It conveys precision as well as the estimated value. A narrow interval generally indicates greater precision than a wide interval, while neither interval alone establishes a causal effect. No confidence interval for the primary outcome or secondary outcomes is reported in the registry record. Without an estimate and its uncertainty, the precision of the study’s findings cannot be assessed from the record.
A p-value, when used, describes how unusual data at least as incompatible with a specified null model would be if that model and the analysis assumptions were correct. It is not a measure of clinical importance, the probability that a treatment works, or a substitute for an effect estimate. The registry record does not report p-values or an analysis plan specifying hypothesis tests.
What do planning calculations mean?
Planning calculations are prospective illustrations of the sample size that could be needed under specified assumptions. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and a stated fraction of an observed effect as the effect to detect. Such calculations are not evidence that a completed study had a particular probability of detecting an effect. They are not observed power.
Those planning assumptions should not be mistaken for the design of ACT II. The registry record describes a non-interventional study and does not report a randomized allocation or a like-for-like control comparison. It says allocation was not stated. Thus, assumptions about equal allocation between two arms do not establish that this study used such an allocation. The record also does not report its own sample-size justification. Planning outputs, if considered, are hypothetical illustrations and should not be interpreted as a retrospective assessment of the study’s ability to detect a treatment effect.
Why can count data need special care?
For count outcomes, the statistical model depends on the way events arise and on how variable counts are across observations. In general, over-dispersion occurs when count variability exceeds what a simple model assumes. If ignored, it can lead to uncertainty estimates that are too small. The primary outcome is a participant count, not a reported rate of recurrent events, and the registry record does not report a model or an over-dispersion assessment. This general concept should not be taken to mean that over-dispersion occurred in this study.
More broadly, statistical interpretation requires the outcome estimate, the population analyzed, the denominator, and a description of the analysis. The registry record does not report those elements for the primary outcome. Statistical concepts can explain what would be needed for interpretation, but cannot fill in missing results or methods.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists a primary outcome and secondary outcomes covering changes from baseline in total cholesterol, LDL-C, HDL-C, and triglycerides at Month 3 and Month 12. It does not report a multiplicity plan, such as which comparisons were confirmatory or how the possibility of multiple statistical tests was handled. In general, when several outcomes or time points are examined, the chance of at least one apparently unusual result can increase if each is tested separately without adjustment. Whether and how that concern was addressed in this study is not reported in the registry record.
The record lists no analyses and gives no numerical results for the outcomes in the information available for this account. It does not report an analysis population, outcome-specific denominators, or whether analyses followed an intention-to-treat, per-protocol, or other rule. Because the study is described as non-interventional, the randomized-trial term intention-to-treat should not be assumed to describe its analysis.
Missing-data handling is also not reported in the registry record. In general, missing outcome measurements can affect both the estimated outcome and its precision, especially if the participants with missing data differ from those with observed data. Different approaches make different assumptions, and the chosen approach should be stated. The record does not say whether missing measurements occurred, how many were missing, or how any missingness was handled. No specific missing-data method or analysis population can therefore be inferred.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| All Participants | 3 | 1682 | 0.2% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| All Participants | 0 of 1682 |
Most frequent serious adverse event terms
| Event term | Organ system | All Participants |
|---|---|---|
| Cholecystitis | Hepatobiliary disorders | 1 of 1682 |
| Basal Cell Carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 1682 |
| Bronchial Neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 1682 |
Serious events with the highest arm-level rate: cholecystitis (0.1%), basal cell carcinoma (0.1%), bronchial neoplasm (0.1%).
The registry record lists serious adverse events for the All Participants group, with 1682 at risk and 3 affected. It lists other adverse events with 1682 at risk and 0 affected. These are registry counts; the record does not provide additional detail about event timing, duration, severity beyond the serious classification, or whether events were judged related to ezetimibe.
The serious-event terms listed are Cholecystitis, Basal Cell Carcinoma, and Bronchial Neoplasm, each recorded as 0.1%. These entries identify reported terms and their registry percentages. They should not be read as evidence of causation or as a complete clinical account of each event. The registry record does not describe event-level circumstances or provide a comparison group.
Counts at risk indicate the group listed for safety reporting, but do not establish how safety follow-up was conducted or whether all participants had the same observation time. Because the study was non-interventional and has no reported like-for-like control comparison, the safety figures describe events recorded in the study group; they do not estimate an excess risk attributable to treatment. The registry record does not report a causal safety analysis.
12. What the Result Does, and Does Not, Mean
The record describes a routine-care follow-up in which ezetimibe was chosen for participants with coronary heart disease already receiving a statin and not meeting LDL-C targets. It establishes the primary question: the number achieving individual LDL-C targets through up to 12 months. It also defines the target thresholds by risk category and lists lipid measures for follow-up.
What the record does not establish is the observed answer to the primary question. The number achieving target is not reported in the registry record. Numerical results for the listed secondary outcomes, uncertainty estimates, and analyses are also not reported. The endpoint description and the completed study status cannot substitute for outcome data. Consequently, the record does not show the magnitude or precision of any change in cholesterol measures or target attainment.
The design also limits what any observed before-and-after change could mean. Participants were not described as randomly assigned, and the registry record warns that the arms are not a like-for-like control comparison. Without an appropriate counterfactual comparison, changes over follow-up cannot isolate the effect of ezetimibe from other influences. The observed course of care, if numerical results were available, would be descriptive rather than a definitive causal estimate.
The safety information reports 3 serious adverse events among 1682 at risk and 0 other adverse events among 1682 at risk, with three serious-event terms listed at 0.1% each. These entries describe registry reporting; they do not establish that treatment caused or prevented any event. There is no control comparison to support a relative safety conclusion.
In short, this record is useful for identifying the population, intervention context, target definitions, and intended outcomes. It does not provide enough reported outcome or analysis information to determine the frequency of target attainment, quantify changes, or estimate a causal treatment effect. It should be read as a description of the study record, not as proof that a treatment works or does not work.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of the distinction between a clinical target and a causal treatment effect. The primary endpoint asks whether participants reached targets assigned by risk category. That outcome can describe target attainment in routine care, but it is not itself a comparison of what would happen with ezetimibe versus another strategy. The registry record’s warning that the arms are not a like-for-like control comparison is central to interpreting the design.
The target definitions also illustrate why outcome construction matters. High-risk and very high-risk participants had different LDL-C thresholds, so the endpoint combines target attainment relative to each participant’s category rather than using a single threshold for everyone. Understanding a reported count would require knowing how participants were categorized, how many were assessed, and how missing assessments were handled. Those details and the primary result are not reported in the registry record.
The study also lists several lipid outcomes at different follow-up times. This makes transparent reporting of the analysis plan and multiplicity handling important: a collection of outcomes can support a broader description, but interpretation depends on distinguishing prespecified primary questions from additional analyses. The registry record does not report how this was handled, so the listed outcomes cannot be ranked by statistical evidence or interpreted as a set of confirmed findings.
Finally, the record demonstrates why enrollment and completion status are not substitutes for analyzable outcome data. Enrollment is listed as 1682, but outcome-specific denominators, estimates, and uncertainty are absent. Without them, neither the frequency of target attainment nor the precision of that estimate can be assessed. The statistical importance of the record lies in the questions and design features it documents, as well as the limits created by unreported analyses.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
A central limitation is that the registry record does not report the primary outcome result or numerical results for the secondary outcomes. It names the measures and follow-up windows but gives no estimates or uncertainty intervals. The record therefore cannot support a quantitative account of target attainment or lipid changes.
The study is non-interventional, and the registry record states that allocation was not stated and that the arms are not a like-for-like control comparison. This limits causal interpretation. Treatment selection in routine medical care can be associated with participants’ characteristics and care decisions; the record does not report adjustment methods that might address such differences. No adjusted treatment effect should be inferred.
Important analysis details are not reported in the registry record. These include the analysis population, outcome-specific denominators, missing-data handling, statistical methods, multiplicity handling, and sample-size justification. The record does not state whether the risk categories were assigned consistently at enrollment or provide their distribution. It also does not describe how LDL-C target attainment was assessed when a measurement was unavailable.
The enrollment entry of 1682 should not be assumed to be the denominator for every outcome. The registry record does not say how many participants contributed measurements at each follow-up point. Similarly, a completed status does not establish complete follow-up or complete outcome reporting.
Safety interpretation is limited by the absence of event-level detail and a suitable comparison group. The registry record lists counts and serious-event terms, but does not report timing, duration, attribution, or a comparative safety analysis. These limitations apply to interpretation of the record and do not establish that unreported events or analyses did or did not occur.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Effect of Ezetimibe Treatment on Low-density Lipoprotein Cholesterol (LDL-C) Levels in Participants With Coronary Heart Disease (CHD) Already Treated With a Statin (MK-0653A-205 AM1) — NCT01381679.
- Registry record last updated 2022-02-09; status last verified 2022-02.
- Results first posted 2012-03-22.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The registry record describes ACT II, a completed, non-interventional longitudinal follow-up of participants with coronary heart disease already treated with a statin. Ezetimibe was chosen for participants whose LDL-C targets had not been achieved. Enrollment is listed as 1682; the recorded start is 2009-05 and primary completion is 2010-12.
The primary outcome was the number achieving individual LDL-C targets through up to 12 months. Targets were 100 mg/dL for high-risk participants and 70 mg/dL for very high-risk participants under the Austrian Cholesterol Consensus 2007. Secondary outcomes listed changes from baseline in total cholesterol, LDL-C, HDL-C, and triglycerides at Month 3 and Month 12.
The primary and secondary numerical results, analyses, analysis populations, and missing-data methods are not reported in the registry record. The record cautions that there is no like-for-like control comparison. Safety reporting lists 3 serious adverse events and 0 other adverse events among 1682 at risk; causal interpretation is not supported by the recorded design.