This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record.
1. Trial at a Glance
FAME 2 is a completed 10-year follow-up study registered under NCT06159231 in patients with coronary artery disease. The registry identifies a single primary endpoint: the rate of major adverse cardiac events after 10 years of follow-up, with MACE defined as all-cause death, documented myocardial infarction, or unplanned hospitalization leading to urgent revascularization.
| Feature | FAME 2 |
|---|---|
| Study acronym | FAME 2 |
| Study title | FAME II-10-year Follow-Up |
| Condition | Coronary Artery Disease |
| Status | COMPLETED |
| Enrollment | 888 |
| Lead sponsor | CoreAalst BV |
| Sponsor type | INDUSTRY |
| Start date | 2023-04-25 |
| Primary completion date | 2024-05-15 |
| ClinicalTrials.gov | NCT06159231 |
2. Clinical Question
The registry's primary question is centered on the long-term occurrence of major adverse cardiac events after 10 years of follow-up in patients with coronary artery disease. The primary endpoint is a composite event measure rather than a single clinical outcome.
Population
The study enrolled 888 participants with coronary artery disease.
Intervention
The ClinicalTrials.gov record does not report the intervention details in the available study information.
Comparator
The ClinicalTrials.gov record does not report the comparator details in the available study information.
Primary question
What is the rate of major adverse cardiac events after 10 years of follow-up?
3. Trial Design
The registry identifies FAME II-10-year Follow-Up as a completed study beginning on 2023-04-25 and reaching primary completion on 2024-05-15, with an enrollment of 888 participants.
The available registry information does not specify a randomization ratio, treatment arms, crossover, stratification factors, interim analyses, multiplicity procedures, or missing-data methods. These are important design features when interpreting comparative trials, but they should only be attributed to FAME 2 if they are documented in the relevant trial record or statistical documents.
4. Primary Endpoint
| Endpoint | Registry definition | Time frame |
|---|---|---|
| The rate of major adverse cardiac events after 10 years of follow-up | 10-year major adverse cardiac event rate (MACE, defined as all-cause death, documented myocardial infarction, unplanned hospitalization leading to urgent revascularization). | 10 years |
The endpoint is a composite. A participant contributes a MACE event if one of the listed component outcomes occurs: all-cause death, documented myocardial infarction, or unplanned hospitalization leading to urgent revascularization.
The composite endpoint treats the occurrence of any qualifying component as an event for the purpose of the MACE outcome. The clinical frequency and importance of individual components can nevertheless differ substantially.
5. Planned Analysis
The registry identifies the 10-year major adverse cardiac event rate as the primary endpoint, but no formal statistical analyses are posted in the ClinicalTrials.gov record. Results have not been posted on ClinicalTrials.gov.
How a 10-year MACE endpoint is typically analysed
For a fixed 10-year endpoint, one straightforward summary is the proportion of participants who experience at least one qualifying MACE by 10 years. If all participants have complete ascertainment through the specified time point, the analysis can be expressed as a cumulative event proportion:
The corresponding percentage gives an absolute description of how frequently the composite endpoint occurred over the specified follow-up horizon.
When participants have different amounts of observed follow-up or are censored before 10 years, a time-to-event approach is generally more informative. Kaplan-Meier estimation can account for right-censored observations and estimate the probability of remaining free of the event over time. The complement of that event-free survival function can then provide a time-specific cumulative event estimate under the assumptions of the method.
Here, S(t) represents the estimated probability of remaining free of the event through time t. The appropriate calculation depends on the actual censoring and event structure.
If the original study contains randomized treatment groups, a comparative analysis would ordinarily be based on the randomized assignment and could include a between-group comparison of time-to-first MACE. Depending on the prespecified analysis plan, this could involve Kaplan-Meier curves, a log-rank test, and a Cox proportional-hazards model with a hazard ratio and confidence interval. Those methods are standard options for time-to-event outcomes; the available registry record does not state that they were used for FAME 2.
Why the composite endpoint matters
A composite endpoint can increase the number of observed events, which may provide more statistical information than a rarer individual component. However, interpretation requires attention to the individual components because a composite can be driven primarily by one component while other components occur less frequently.
For FAME 2, the registry-defined components are all-cause death, documented myocardial infarction, and unplanned hospitalization leading to urgent revascularization. A reported overall MACE rate would therefore answer a different question from the rate of death alone or myocardial infarction alone.
6. Statistical Methods Explained
What does a 10-year MACE rate measure?
A 10-year MACE rate describes how frequently participants experience at least one event meeting the composite definition during the specified 10-year follow-up period. It is an absolute measure over a defined time horizon, rather than a relative treatment effect.
Why use a composite endpoint?
Combining clinically defined outcomes can increase the number of events available for analysis. That can improve statistical information when individual components are relatively uncommon. The tradeoff is interpretability: the composite result does not tell the reader whether each component contributed equally to the observed event rate.
Why might Kaplan-Meier analysis be appropriate?
Long-term clinical follow-up commonly includes participants who are observed for different lengths of time. Kaplan-Meier estimation accommodates right censoring and uses the available follow-up information to estimate event-free survival over time. This is particularly useful when the exact timing of MACE events is available.
What would a hazard ratio add to a 10-year event rate?
A hazard ratio provides a relative comparison of the instantaneous event rates between two groups over follow-up under a Cox-model framework. It is different from an absolute 10-year event percentage. For example, two groups can have a relative hazard ratio while also having clinically important differences in their absolute cumulative event probabilities.
Why is the definition of MACE important?
The exact component definitions determine which observations count as events. In this registry, MACE includes all-cause death, documented myocardial infarction, and unplanned hospitalization leading to urgent revascularization. Changing a component definition or its adjudication rules can change the observed endpoint rate.
Why should the component outcomes also be examined?
A composite endpoint can conceal differences in its components. If one component occurs much more often than the others, the overall MACE result will largely reflect that component. Component-specific results therefore help explain what is actually contributing to the composite endpoint, although they should be interpreted within the prespecified statistical framework.
7. Interpreting a Future 10-Year MACE Result
Because the registry currently provides no posted statistical estimates, the most useful way to understand the primary endpoint is to distinguish several quantities that could appear in a completed analysis.
Absolute event rate
The percentage of participants experiencing at least one qualifying MACE by 10 years. This directly describes the frequency of the composite outcome over the specified horizon.
Event-free survival
The estimated probability of remaining free of MACE through a specified time. Its complement can describe cumulative event probability under a time-to-event framework.
Hazard ratio
If groups are compared using a Cox model, the hazard ratio describes a relative event-rate comparison rather than the percentage of participants who experience MACE.
Confidence interval
A confidence interval quantifies statistical uncertainty around an estimated effect. It does not describe the range of outcomes that individual patients will experience.
A future reported 10-year MACE percentage would describe an absolute cumulative outcome over a specified period. It would not, by itself, establish a causal treatment effect or show how the risk compares with another treatment group.
A hazard ratio below 1 would indicate a lower estimated instantaneous event rate in the numerator group relative to the reference group under the fitted model. It would not mean that the same percentage of participants avoided MACE, nor would it be interchangeable with a difference in 10-year event rates.
A point estimate alone does not show how precisely the underlying treatment or event-rate comparison has been estimated. A confidence interval provides the corresponding statistical uncertainty and should be considered alongside the effect estimate rather than treated as an optional add-on.
8. Limitations
- No posted statistical analyses: The ClinicalTrials.gov record does not contain formal statistical analysis results for the registered primary endpoint.
- No posted outcome estimates: The record does not report a 10-year MACE event count, event percentage, confidence interval, hazard ratio, or p-value.
- Composite endpoint: MACE combines three distinct outcomes, so an overall rate does not identify the contribution of each component.
- Incomplete comparative design information: The available record does not specify intervention or comparator details, randomization, allocation, or blinding.
- Unreported analysis population: The available record does not specify how participants with incomplete follow-up or other analysis-population issues were handled.
- Unreported censoring strategy: The available record does not state how censoring or loss to follow-up was handled for the 10-year endpoint.
- Unreported multiplicity: The available record does not describe any multiplicity adjustment or endpoint hierarchy beyond identifying the registered primary endpoint.
- Unreported interim monitoring: The available record does not describe interim analyses or alpha-spending procedures.
- Component interpretation: Even with a reported MACE estimate, interpretation would benefit from separate reporting of its death, myocardial infarction, and urgent-revascularization components.
9. Why This Trial Matters Statistically
FAME 2 is a useful teaching example because its registered primary endpoint illustrates a central problem in long-term cardiovascular trial analysis: a clinically meaningful outcome must be translated into a precisely defined statistical estimand.
| Concept | How it applies to the registered endpoint |
|---|---|
| Composite endpoint | MACE combines all-cause death, documented myocardial infarction, and unplanned hospitalization leading to urgent revascularization. |
| Time horizon | The primary endpoint is explicitly defined after 10 years of follow-up. |
| Absolute risk | A 10-year event proportion would describe the cumulative frequency of MACE over the specified horizon. |
| Time-to-event analysis | If exact event and censoring times are available, survival methods can account for unequal follow-up. |
| Censoring | Participants who do not have complete observation through 10 years may require time-to-event methods rather than a simple complete-case proportion. |
| Hazard ratio | If treatment groups are compared using a Cox model, the HR would provide a relative time-to-event measure distinct from the 10-year absolute rate. |
| Confidence interval | Uncertainty around an estimated event rate or comparative effect is essential for statistical interpretation. |
| Component analysis | The composite result should be understood alongside its individual death, myocardial infarction, and urgent-revascularization components. |
10. The Difference Between a Rate and a Treatment Effect
The phrase 10-year MACE rate describes the occurrence of an outcome over time. It does not inherently specify a comparison between two treatment strategies.
This distinction is fundamental. An absolute event rate answers a question such as how many participants experienced MACE by 10 years? A risk difference compares two absolute probabilities. A risk ratio compares two probabilities multiplicatively. A hazard ratio compares instantaneous event rates under a time-to-event model. These measures can all describe the same underlying clinical experience from different statistical perspectives, but they are not interchangeable.
Risk ratio = p1 / p0
Hazard ratio = estimated instantaneous event-rate ratio
The first two quantities are based on cumulative probabilities over a specified horizon. The third is a model-based time-to-event comparison.
For a 10-year cardiovascular endpoint, reporting both absolute and relative measures can be especially informative when a comparative analysis is available. Absolute event probabilities communicate the clinical frequency of the outcome, while relative measures describe the relationship between groups.
11. Composite Endpoint Interpretation
The three components of the registered MACE definition have different clinical meanings: all-cause death is a mortality outcome, documented myocardial infarction is an acute ischemic event, and unplanned hospitalization leading to urgent revascularization reflects a clinically consequential need for urgent intervention.
Statistically, however, the primary composite treats the first qualifying component as the occurrence of MACE. This means that a participant who experiences more than one component can still be counted as one participant with a first MACE event in a typical time-to-first-event analysis.
First-event perspective
A time-to-first-MACE analysis focuses on the time until the first qualifying component occurs. Recurrent events would require a different statistical framework.
Component balance
The overall composite rate does not reveal whether death, myocardial infarction, or urgent revascularization was the dominant contributor.
Clinical interpretation
A composite can be statistically efficient while still requiring component-level interpretation to understand what the result means clinically.
Endpoint consistency
Consistent definitions and event ascertainment are essential because changes in component definitions can change the observed composite rate.
12. Long-Term Follow-Up and Censoring
A 10-year endpoint creates a natural statistical question about incomplete observation. Not every participant necessarily contributes the same amount of observable follow-up in a long-term study. Participants can become lost to follow-up, withdraw, or otherwise stop contributing event information before the target time point.
A simple proportion calculated only among participants with complete 10-year follow-up can be biased if the reason for incomplete follow-up is related to outcome risk. Time-to-event methods provide a framework for using the information available up to the censoring time, provided their assumptions are appropriate.
13. What the Registry Reports — and What It Does Not
| Item | Registry status |
|---|---|
| Study acronym | FAME 2 |
| Study title | FAME II-10-year Follow-Up |
| Condition | Coronary Artery Disease |
| Enrollment | 888 |
| Study status | COMPLETED |
| Primary endpoint | 10-year major adverse cardiac event rate |
| MACE definition | All-cause death, documented myocardial infarction, or unplanned hospitalization leading to urgent revascularization |
| Primary endpoint time frame | 10 years |
| Posted statistical analyses | None |
| 10-year event estimate | Not reported in the registry |
| Confidence interval | Not reported in the registry |
| p-value | Not reported in the registry |
This distinction is important for statistical reading. The existence of a prespecified endpoint tells us what outcome the study was designed to assess, while a statistical result requires an observed event count or time-to-event dataset together with the analysis procedure used to estimate the endpoint.
14. Statistical Interpretation vs Clinical Interpretation
Statistical interpretation
The registered primary endpoint is a 10-year composite MACE outcome. Appropriate analysis depends on whether complete 10-year follow-up is available and on the underlying event and censoring structure.
Clinical interpretation
The endpoint combines death, documented myocardial infarction, and unplanned hospitalization leading to urgent revascularization, so any eventual result should be considered together with its individual components.
The two perspectives should remain distinct. Statistical analysis determines how the observed data support an estimate and how uncertain that estimate is. Clinical interpretation considers what the endpoint represents for patients and how its components contribute to the overall outcome.
15. A Framework for Reading the Final Analysis
When formal FAME 2 results are available, a statistically complete interpretation should begin with the exact analysis population and endpoint definition, then move through the absolute event experience, time-to-event estimates if applicable, comparative effect measures if applicable, and uncertainty.
Define the estimand
Identify exactly which participants, treatment comparison if any, outcome definition, and 10-year time horizon are being analysed.
Describe the event experience
Report the number and proportion of participants experiencing MACE and, where available, the individual component counts.
Account for follow-up
Determine whether participants had complete 10-year observation or whether censoring and unequal follow-up require time-to-event analysis.
Quantify uncertainty
Present confidence intervals around the principal event-rate or treatment-effect estimates.
Interpret the components
Examine death, myocardial infarction, and urgent-revascularization components rather than interpreting the composite in isolation.
16. Why a Missing P-Value Is Not the Same as a Negative Result
No p-value is reported for the primary endpoint in the available ClinicalTrials.gov record. That absence should not be interpreted as evidence for or against a treatment effect. A p-value can only be interpreted in the context of a specified statistical comparison, null hypothesis, analysis population, and test procedure.
Likewise, the absence of a reported hazard ratio does not establish that no hazard ratio exists in another statistical report. It simply means that the available registry record does not post one. The same distinction applies to confidence intervals, event counts, and subgroup analyses.
17. Why This Trial Is Statistically Educational
The FAME 2 registry entry provides a compact example of how a clinically defined long-term endpoint becomes a statistical estimand. The endpoint has a clear horizon, a composite definition, and a clinically recognizable set of components, yet the appropriate analysis still depends on the structure of the underlying follow-up data.
The most important lesson is that an endpoint name alone does not determine the statistical method. A 10-year MACE endpoint could be summarized as a cumulative proportion if complete follow-up were available, or analysed with time-to-event methods if censoring and event timing were central to the data structure. The correct approach is determined by the prespecified estimand and the actual observation process.
| Statistical question | Why it matters |
|---|---|
| What counts as MACE? | Determines which observations qualify as primary endpoint events. |
| When does follow-up end? | Defines the 10-year estimand and the relevant event horizon. |
| How much follow-up is observed? | Determines whether simple cumulative proportions are adequate or censoring must be incorporated. |
| How are treatment groups defined? | Required for a comparative treatment-effect estimand. |
| How is uncertainty quantified? | Determines how precisely the event rate or treatment effect has been estimated. |
| Which component drives MACE? | Clarifies the clinical meaning of the composite result. |
18. Sources
- ClinicalTrials.gov: NCT06159231.
- PubMed: PubMed record.
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19. Record Summary
FAME 2 is a completed 10-year follow-up study in coronary artery disease with an enrollment of 888 participants. Its registered primary endpoint is the rate of major adverse cardiac events after 10 years of follow-up, with MACE defined as all-cause death, documented myocardial infarction, or unplanned hospitalization leading to urgent revascularization.
Statistically, the endpoint illustrates the distinction between an absolute long-term event rate and comparative time-to-event measures such as hazard ratios. It also demonstrates why composite endpoints require component-level interpretation and why censoring, follow-up completeness, analysis populations, and uncertainty intervals are central to the eventual statistical interpretation.