A Study of Stress Echocardiography in Post-Menopausal Women at Risk for Coronary Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Stress Echocardiography in Post-Menopausal Women at Risk for Coronary Disease (NCT00162370), a na phase 4 study. The primary outcome is Number of Participants With Abnormal Contrast Stress Echocardiography and With Future Major Adverse Cardiac Events (MACE) at 2 and 5 Years Follow-Up.

2. Clinical Question

The clinical question is therefore prognostic: whether abnormal stress-echo findings identify participants who later experience an event included in the study's MACE definition. MACE includes cardiac death, myocardial infarction, cardiac revascularization, hospitalization for chest pain or to rule out myocardial infarction, development of typical angina, and development of heart failure. These components vary in clinical severity and in how they are identified. The record does not report component-specific results, so it is not possible to tell whether any relationship with imaging findings was driven by a particular type of event. Nor does the registry record report how abnormal imaging was classified, how follow-up events were confirmed, or the number of participants contributing information at each follow-up point. The study question should not be read as a randomized test of whether imaging or Definity changes the incidence of cardiac events.

3. Trial Design

The registry describes a completed Phase 4 study sponsored by Lantheus Medical Imaging. It lists an enrollment of 400 and a single-group model, with allocation recorded as not applicable and masking recorded as none. The study began in 2004-04, and primary completion was recorded in 2012-09. The record does not report the recruitment process, the number screened or excluded, or whether all enrolled participants completed the imaging and follow-up procedures.

Participants received a baseline unenhanced imaging session and Definity-enhanced rest and stress echocardiography. Stress imaging used treadmill exercise or dobutamine. The primary-outcome description says images were evaluated for wall-motion abnormalities and related to later patient history. This is an observational prognostic structure within a single enrolled group: the central contrast is between imaging status and subsequent event status, not between randomly assigned treatments.

The record includes a list of secondary outcomes concerning ECG findings, natriuretic peptides, brachial artery reactivity, calcium scores, angiography, wall-motion abnormalities, and MACE during follow-up. Although 12 outcome measures are listed, the registry record does not report their results or explain how each was analyzed. Two analyses are listed, but their definitions, populations, and statistical procedures are not reported in the registry record.

Because there is no randomized control group, the design cannot by itself isolate the effect of receiving contrast imaging from other influences. The study can address whether baseline imaging findings correspond to later events among the participants observed, subject to complete and reliable measurement of both. It cannot establish that using the imaging test prevents events, or that one imaging strategy is superior to another. The record does not report a statistical analysis plan, a sample-size justification, interim analyses, or a prespecified method for handling incomplete follow-up.

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.

Completed Echocardiography Imaging

Efficacy Population

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Subject has received a physical exam, completed patient history profile, undergone the protocol-specific unenhanced and DEFINITY enhanced rest and stress echocardiography, had the necessary blood work for the study and participated in 2 year or 5 year follow up

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.

Population: Peri- or post-menopausal female subjects between 40 and 65 years of age with an intermediate likelihood of CAD who are scheduled to undergo stress echocardiography

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Abnormal Contrast Stress Echocardiography and With Future Major Adverse Cardiac Events (MACE) at 2 and 5 Years Follow-Up, measured over 2 year and 5 year follow up.

The primary endpoint is the count of participants described as having abnormal contrast stress echocardiography and future MACE at 2-year and 5-year follow-up. It concerns a relationship between a baseline imaging finding and later clinical events. The imaging component is based on assessment of wall-motion abnormalities. MACE is defined broadly in the registry record to include cardiac death, myocardial infarction, cardiac revascularization by PCI or CABG, hospitalization for chest pain or to rule out myocardial infarction, development of typical angina, and development of heart failure.

Counts can communicate how many participants meet a defined outcome, but a count alone does not quantify the strength or precision of an association. Interpretation also requires knowing the relevant denominator, how participants were classified, whether outcomes were observed consistently, and how much follow-up information was available. Those details and the primary outcome counts are not reported in the registry record.

A composite endpoint can capture several types of events, but its overall count does not show which components occurred or whether components contributed similarly. In this study, the component-specific counts are not reported in the registry record. The endpoint is intended to evaluate the potential of stress echocardiography for identifying participants at higher risk of future cardiac events; the registry description does not establish that the test changes risk or improves outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record lists two analyses, but their methods and results are not reported in the registry record. No statistical analysis plan, model specification, adjustment strategy, or method for handling incomplete observations is described. The interpretation must therefore distinguish the study question from analyses that cannot be verified from the record.

What would a count describe?

General statistical explanation: a count is the number of participants meeting a stated definition. For this endpoint, the definition involves both abnormal contrast stress echocardiography and future MACE. A count is interpretable only in context. Readers need to know the population from which it arose, the number eligible for assessment, and how many had usable imaging and follow-up data. Counts can change when follow-up is incomplete or when outcome definitions are applied differently. The registry record does not report the endpoint counts, analysis denominators, or missing-data handling.

For a prognostic question, it is generally useful to compare outcome occurrence across imaging categories and to report both the size of the association and its uncertainty. A confidence interval describes a range of estimates compatible with the data and the statistical model, and can show whether an estimate is precise or uncertain. A p-value, when used, addresses compatibility with a specified null model; it does not measure the probability that a hypothesis is true or the clinical importance of an association. No confidence interval or p-value for the primary outcome is reported in the registry record.

What does the single-group structure allow?

General statistical explanation: when participants are not randomized to a control condition, comparisons within the group are susceptible to confounding. For example, participants with abnormal imaging may differ from those with normal imaging in underlying characteristics that also relate to later events. Statistical adjustment can sometimes address measured differences, but it cannot automatically remove unmeasured or poorly measured confounding. The record does not report whether the primary analysis was adjusted, which variables might have been considered, or how model assumptions were checked.

The study also does not provide a randomized contrast between Definity and no Definity. The protocol describes unenhanced baseline imaging as well as enhanced rest and stress imaging, but that does not constitute a randomized comparison of imaging strategies. Without a prespecified comparison and analysis, any contrast among observed imaging findings should be understood as an association, not as evidence that the imaging approach caused a change in later events.

How should the follow-up outcome be understood?

General statistical explanation: follow-up outcomes can be analyzed as counts or as time-to-event data. A count over a defined follow-up period does not account for differences in how long each participant was observed. Time-to-event methods can incorporate the timing of events and censoring, but require clear definitions of time origin, event ascertainment, and censoring. The registry record gives 2-year and 5-year follow-up points but does not report whether the analysis used fixed-time counts, time-to-event methods, or another approach. No event times, censoring rules, or follow-up completeness measures are reported.

The composite MACE definition combines multiple outcomes. General statistical explanation: composite endpoints can increase the number of observed outcomes and capture a broad range of clinically relevant experiences. They can also make interpretation less straightforward if components differ in severity, frequency, or how consistently they are identified. Reporting component counts alongside the composite helps readers understand what contributes to an overall result. Component-specific results are not reported in the registry record.

The record describes sample-size planning assumptions as an illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. The record also distinguishes total events for time-to-event planning from participants per arm for other planning. These are planning assumptions, not a description of the trial's actual single-group design. The planning values and observed effect are not reported in the registry record, and the illustrations should not be treated as observed power or as the trial's own sample-size justification. The registry record does not report a protocol-based justification for enrollment of 400.

General statistical explanation: over-dispersion matters when the observed variation in counts exceeds what a chosen model assumes. In such cases, standard errors from a model that assumes less variation may be too small, making uncertainty appear narrower than it is. The primary endpoint is described as a count of participants, but no count-model analysis or dispersion estimate is reported; over-dispersion should not be presumed to have been assessed. A suitable analysis depends on the actual outcome structure and the prespecified estimand, neither of which is fully documented in the registry record.

Because the record does not provide analysis methods or numerical primary results, it is not possible to reproduce or evaluate the statistical analysis. The registry record does not report any recalculated estimate or discrepancy requiring a comparison with a sponsor analysis. Where a sponsor's own analysis is available, that analysis takes precedence over simple unadjusted re-calculations from summary statistics; no such numerical comparison is available in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 12 outcome measures, including the primary MACE outcome and secondary outcomes involving ECG, biomarkers, vascular reactivity, calcium scores, angiography, and wall-motion abnormalities. It also lists two analyses. The analysis details are not reported in the registry record, including which outcomes were tested, whether analyses were prespecified, and whether any results were adjusted for multiple comparisons.

General statistical explanation: when many outcomes or subgroup comparisons are examined, the chance of finding at least one apparently unusual result can increase, even if no strong underlying relationship exists. Multiplicity procedures or a clearly prespecified hierarchy can help readers interpret a family of tests. The record does not report whether such procedures or a hierarchy were used, so the extent to which multiplicity was addressed is unknown. No specific significance claim can be evaluated because the primary and secondary outcome results are not reported.

Missing data are also important in follow-up studies. Participants may have incomplete imaging, unknown event status, or follow-up that ends before an assessment point. These situations can affect both the number analyzed and the apparent event frequency. The registry record does not report the number with complete follow-up at the 2-year or 5-year assessment, reasons for missing observations, or a method for handling missing data. It does not report whether participants were analyzed according to a defined analysis population or whether any sensitivity analyses were conducted.

The primary-outcome description refers to participants who completed study procedures and participated in follow-up, but the record does not define an analysis population in enough detail to determine who contributed to each result. It is therefore not possible to assess selection due to incomplete participation or to judge whether the analyzed participants represent the enrolled group. These omissions limit assessment of both bias and precision.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry adverse-event summary lists the Definity group with 400 at risk for serious adverse events and 0 participants affected in that category. For other adverse events, it lists 400 at risk and 6 participants affected. These are separate categories in the registry summary; the other-adverse-event count should not be treated as a serious-event count. The record does not provide the specific terms for the events in either category, and it does not report a death count.

These figures describe the safety summary as recorded, not the primary prognostic endpoint. The primary endpoint concerns abnormal stress echocardiography and future MACE, and its results are not reported in the registry record. The safety figures also do not establish whether an event was caused by Definity or by an imaging procedure. A single-group summary has no randomized control group for estimating comparative safety.

General statistical explanation: an affected-participant count is not a complete description of safety. Interpretation can depend on event definitions, severity, timing, duration of observation, and whether participants could experience more than one event. The registry record does not report these details for the adverse-event summary. The listed counts should therefore be read narrowly and should not be taken as a comprehensive account of event types, causal attribution, or risk beyond the recorded categories.

12. What the Result Does, and Does Not, Mean

The record establishes that the study addressed the potential of stress echocardiography to identify peri- or post-menopausal women at intermediate pre-test likelihood of coronary artery disease who might later experience cardiac events. It describes baseline imaging, Definity-enhanced rest and stress echocardiography, and follow-up at 2-year and 5-year points. It also gives a definition of MACE and lists related secondary outcomes.

The record does not report the primary outcome counts or an estimate of association between abnormal imaging and later MACE. It therefore does not show whether abnormal imaging was more common among participants who experienced events, how large any association was, or how precisely it was estimated. It also does not report diagnostic performance measures or component-specific MACE findings. No conclusion about the predictive accuracy of the test can be drawn from the information recorded.

The single-group, nonrandomized design is important to interpretation. An association between imaging results and later events would not, on its own, show that imaging caused a difference in events. Nor would it show that performing the test improves outcomes. Such claims would require evidence addressing the effects of using the test, including appropriate comparisons and outcome results, which are not reported in the registry record.

The record also does not establish that one stress method is preferable: treadmill exercise and dobutamine are both described, but comparative results are not reported. The broad composite MACE definition means that an overall outcome count, if available, would need to be interpreted alongside the individual event components. These component results are not reported.

Accordingly, the registry record is informative about the study's intended question and procedures, but not about the magnitude or reliability of the primary result. The adverse-event summary provides limited counts by category, but not event descriptions or causal assessment. Neither those counts nor the stated purpose of the study should be interpreted as proof that the imaging approach improves health outcomes or changes cardiac risk.

13. Why This Trial Matters Statistically

This study is statistically interesting because it asks a prognostic question in a population described as peri- or post-menopausal women with intermediate pre-test likelihood of coronary artery disease. It connects a baseline imaging feature, wall-motion abnormalities during contrast-enhanced stress echocardiography, with a broad set of later cardiac events. Such a question requires attention not only to whether events occurred, but also to how imaging categories were defined, how events were ascertained, and how complete follow-up was.

The single-group design makes the distinction between prediction and treatment effect especially important. An imaging finding might be associated with later events without the imaging procedure itself changing those events. Likewise, an association may be influenced by participant characteristics related to both imaging results and prognosis. Statistical interpretation must therefore be cautious about causal language and attentive to confounding, outcome measurement, and follow-up.

The composite outcome also presents a useful interpretive issue. It groups cardiac death, myocardial infarction, revascularization, hospitalization, angina, and heart failure. General statistical explanation: a composite can capture a wider range of outcomes, but an overall summary may conceal which components drive the result. Component-level reporting and uncertainty measures are important for understanding what an association means.

The registry record is limited in what it makes available for evaluating these issues. It describes the question and lists outcomes, but does not report the primary counts, analysis details, uncertainty estimates, or completeness of follow-up. This makes the study a reminder that a clinically meaningful research question and a completed study status do not, by themselves, allow readers to judge statistical evidence. Transparent outcome reporting and a clearly described analysis are necessary to assess both the size and the credibility of any observed relationship.

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.

The registry record contains the study purpose and broad design, but key details needed to interpret the primary endpoint are not reported in the registry record. These include the primary outcome counts, denominators within imaging categories, estimates of association, and measures of uncertainty. Without them, the direction and precision of the prognostic relationship cannot be evaluated.

The record does not describe how abnormal wall motion was defined, whether image interpretation was standardized, or whether readers were blinded to clinical information. It does not report how MACE events were verified or adjudicated, or provide results for the individual components of the composite. Differences in measurement or ascertainment could affect interpretation, but their extent cannot be assessed.

The single-group, nonrandomized structure does not support a randomized comparison of imaging strategies. The record does not report adjustment methods or the characteristics needed to evaluate confounding between imaging findings and future events. It also does not report the number of participants with complete follow-up at each assessment, reasons for missing information, or methods for handling incomplete follow-up. These omissions prevent assessment of possible selection bias and the effective analysis population.

The protocol description includes treadmill exercise or dobutamine stress, but comparative findings by stress method are not reported. Details about recruitment, eligibility, participant characteristics, and generalizability beyond the described population are also not reported in the registry record. Finally, although the record lists a sample-size planning illustration, it does not report the numerical planning values or a trial-specific sample-size justification. The planning assumptions should not be mistaken for evidence that the completed study had a particular level of power.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Stress Echocardiography in Post-Menopausal Women at Risk for Coronary Disease — NCT00162370.
• Registry record last updated 2021-03-15; status last verified 2021-02.
• Results first posted 2016-12-08.
• 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.

18. Record Summary

The registry record describes a completed Phase 4, single-group study sponsored by Lantheus Medical Imaging, with enrollment of 400. It studied peri- or post-menopausal women with an intermediate pre-test likelihood of coronary artery disease. Participants underwent baseline unenhanced imaging and Definity-enhanced rest and stress echocardiography, with treadmill exercise or dobutamine used for stress imaging.

The primary outcome concerns participants with abnormal contrast stress echocardiography and future MACE at 2-year and 5-year follow-up. MACE includes cardiac death, myocardial infarction, revascularization, hospitalization for chest pain or to rule out myocardial infarction, typical angina, and heart failure. The primary outcome counts, analysis methods, and uncertainty estimates are not reported in the registry record.

The registry lists secondary outcomes and two analyses, but their results and details are not reported. Its adverse-event summary lists 0 participants affected in the serious category and 6 in the other-adverse-event category. The record supports description of the study question and design, but not a judgment about the magnitude or precision of the primary prognostic result.