Ticagrelor With and Without Aspirin in Patients With Diabetes Mellitus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ticagrelor With and Without Aspirin in Patients With Diabetes Mellitus (NCT04484259), a randomized phase 4 study. The primary outcome is P2Y12 Reaction Units (PRU).

2. Clinical Question

The broader study aim was to assess the pharmacodynamic effects of ticagrelor 60 mg with and without aspirin in people with coronary artery disease and compare these regimens with aspirin plus clopidogrel. That aim is about a laboratory measure of platelet aggregation, not a direct comparison of clinical events such as heart attack or bleeding. The registry summary explains that aspirin withdrawal after a brief period of dual antiplatelet therapy has been studied previously, while whether an aspirin-free approach is appropriate after a longer time frame remains a matter of debate. The posted primary endpoint addresses a narrower question: how the regimens compare on PRU at the specified measurement time.

3. Trial Design

The study is registered as a randomized, parallel-group, Phase 4 trial with no masking. The registry lists an enrollment of 105 and a completed status. The recorded start date is 2021-03-31, and the primary completion date is 2024-01-29. The sponsor is the University of Florida. The registry does not report additional details about how randomization was generated, whether allocation was concealed, or why masking was not used.

Three treatment groups are described. The ticagrelor group received ticagrelor 60 mg twice daily as monotherapy. The aspirin plus ticagrelor group received aspirin 81 mg once daily and ticagrelor 60 mg twice daily. The aspirin plus clopidogrel group received aspirin 81 mg once daily and clopidogrel 75 mg once daily. The primary endpoint description focuses on the comparison between ticagrelor monotherapy and aspirin plus ticagrelor; the clopidogrel group provides an additional regimen in the study but is not named as part of that primary comparison.

The primary endpoint is PRU measured at day 10 before dosing. The registry reports group means with 95% confidence intervals: 47.0 PRU (26.0 to 68.0) for ticagrelor, 39.0 PRU (20.0 to 57.0) for aspirin plus ticagrelor, and 136.0 PRU (110.0 to 162.0) for aspirin plus clopidogrel. The corresponding posted group counts are 26, 28, and 27. These are endpoint-specific figures; the registry does not explain how they relate to enrollment or describe the analysis population.

Eligibility criteria, treatment duration beyond the stated endpoint time, adherence assessment, and details of concomitant care are not reported in the registry record. Nor is a fuller protocol description of the design or analysis plan reported. The study's parallel-group structure means the listed treatment regimens are assigned to separate groups, but the registry does not supply further operational details.

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.

Before assignment: 105 patients consented. * 4 screen failures * 16 withdrawn during run in * 4 lost to follow-up before randomization visit

Run-in Phase With Aspirin and Ticagrelor

Reasons for not completing this period:

Run-in Phase With Ticagrelor Monotherapy

Reasons for not completing this period:

Randomized Treatment

Reasons for not completing this period:

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.

6. Primary Endpoint

The registry lists the primary outcome as P2Y12 Reaction Units (PRU), measured over Day 10, pre-dose.

The primary endpoint is P2Y12 Reaction Units, or PRU, measured by the VerifyNow PRU system on day 10 before dosing. The registry describes the endpoint as the trough effect of treatment. PRU is a continuous laboratory measure: a numerical value represents platelet aggregation measured through the assay, rather than a count of clinical events.

According to the registry description, the VerifyNow system uses turbidimetric optical detection. Platelet-induced aggregation changes light transmittance, and the assay uses microbead agglutination induced by adenosine diphosphate. The instrument measures the resulting optical signal and reports it in PRU. The measure is used in this study to compare pharmacodynamic responses to different antiplatelet regimens at a specified time relative to dosing.

Measuring before the next dose is intended to capture the trough measurement described by the registry, rather than a value taken at an unspecified point after dosing. The endpoint is therefore tied to both the assay and the timing of measurement. Differences in PRU can describe differences in this laboratory response, but the endpoint by itself does not establish differences in clinical outcomes or adverse effects. The registry does not report a clinical-outcome endpoint among the posted primary results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous: PRU can take a range of numerical values, and the registry reports a mean for each treatment group. A mean describes the central value of the observed measurements. It does not show the full distribution of individual values, and it can conceal variation or unusual observations. The registry's posted results give confidence intervals around the means rather than a measure of the individual-level spread such as a standard deviation.

What does a confidence interval convey?

In general, a confidence interval describes uncertainty around an estimate under the statistical method used. A narrower interval indicates greater precision under that method; a wider interval indicates less precision. The intervals posted for the three groups are 26.0 to 68.0 PRU, 110.0 to 162.0 PRU, and 20.0 to 57.0 PRU. These are intervals for group means as recorded in the registry. They are not intervals for pairwise differences. A direct treatment contrast has its own estimate and uncertainty, and cannot be recovered simply by comparing the endpoints of separate group intervals.

Why is the comparison definition important?

An inferential result depends on the groups being compared, the direction used to calculate the difference, the analysis population, and the statistical method. The primary endpoint description names aspirin plus ticagrelor versus ticagrelor monotherapy. The registry's reported non-inferiority entry gives a mean difference of 7 and a 95% confidence interval from -23 to 38, but the entry does not make the contrast clear. The registry also does not report the method or a p-value. Without a clear contrast, those numbers cannot be confidently tied to the primary question.

In general, a non-inferiority analysis asks whether the result is sufficiently close to a comparator according to a prespecified margin. That margin defines how large a difference can be while still meeting the non-inferiority criterion. A confidence interval must be evaluated against that boundary, in the appropriate direction, and under the specified analysis plan. The margin and its direction are not reported in the registry record. The reported interval therefore cannot be interpreted as a complete non-inferiority finding on its own.

What does the endpoint timing contribute?

The PRU measurement is specified for day 10 before dosing. In general, timing matters because a pharmacodynamic measurement may vary depending on its position relative to a dose. The registry calls this a trough, pre-dose measurement. Interpretation should stay anchored to that particular time and assay rather than imply a result for other dosing times, longer follow-up, or clinical events.

What information is missing about the analysis?

The registry does not report whether the primary analysis was adjusted, what statistical test or model was used, how missing measurements were handled, or which analysis population was used. It does not describe an intention-to-treat, per-protocol, or other population for the reported comparison. Those details matter especially for non-inferiority, because analysis choices and departures from assigned treatment can affect the interpretation. No assumptions about these methods can be made from the posted summaries alone.

The registry lists one reported analysis and no posted secondary results. That does not establish whether other analyses were planned, performed, or omitted. The number of planned endpoints, the order in which they were tested, and any control of multiplicity are not reported. In general, testing multiple outcomes or comparisons can increase the chance of finding an apparently notable result by chance unless the analysis plan addresses that issue. The record does not provide enough information to determine whether or how that concern was addressed.

How should planning illustrations be read?

In general, a sample-size calculation estimates how many participants may be needed under specified assumptions about the effect, variability, significance level, allocation, and desired power. The planning illustrations associated with this analysis are based on the observed effect, use a two-sided significance level of 0.05, assume equal allocation between two arms, and use a normal approximation. They are illustrations, not evidence of the trial's original design rationale and not observed power. The registry does not report the trial's own sample-size justification, the effect assumption used in its planning, or whether the planned enrollment was based on this endpoint.

These distinctions matter because a calculation based on an observed effect does not demonstrate that a study was adequately designed in advance or that a result has a particular probability of being true. It is a conditional planning exercise. A defensible interpretation of the trial still depends on the prespecified design and analysis details, several of which are not reported in the registry record.

10. Analyses Reported by the Sponsor

The registry's sponsor-reported analysis is labeled non-inferiority and gives a final-values mean difference of 7, with a 95% confidence interval from -23 to 38. It does not report a p-value or a method, and the analysis entry identifies only the ticagrelor group. The comparator and direction of the stated difference are therefore unclear from the registry record.

The posted group summaries give means and 95% confidence intervals for each regimen, but they do not provide enough information to construct or verify the sponsor's stated contrast. The registry record does not flag a discrepancy between the sponsor's analysis and a recalculation. The two-arm comparison is also listed as not estimable from the posted summary information. Consequently, there is no separate unadjusted recalculation to use as an alternative estimate for the sponsor result.

When a discrepancy is identified, the sponsor's own analysis takes precedence. In this record, the main issue is not a conflicting recalculation but limited reporting: the non-inferiority comparison, margin, and analytic method are not specified. The sponsor result should therefore be reported as posted, without treating it as a fully interpretable conclusion about the named primary comparison.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one reported analysis and no posted secondary results. It records four outcome measures, but the analysis details for those measures are not reported. The number of planned comparisons, whether the primary endpoint was tested only once, and whether any multiplicity adjustment was planned or used are not reported in the registry record. In general, multiplicity matters when several outcomes, time points, or treatment contrasts are tested: without an appropriate plan, the chance of a false-positive finding can increase. The record does not establish whether this concern applied or how it was handled.

Missing-data procedures are not reported. The registry does not say whether all randomized participants had a day 10 PRU measurement, how unavailable measurements were treated, or whether any imputation or sensitivity analysis was performed. The group counts accompanying the endpoint summaries do not, by themselves, explain why those counts differ across arms or how they relate to the recorded enrollment.

The analysis population is also not reported. There is no description of whether the comparison used all randomized participants, participants who received treatment, participants with an available endpoint measurement, or another defined group. Such definitions are important for interpreting randomized comparisons and are particularly relevant to non-inferiority analyses. The registry does not report adherence or protocol-deviation handling for the primary endpoint.

The trial's sample-size justification, interim-analysis plan, and detailed statistical analysis plan are not reported in the registry record. The planning illustrations based on the observed effect should not be read as evidence of the original design assumptions or as observed power. With these reporting gaps, the posted endpoint summaries remain interpretable as group-level descriptive results, but the completeness and robustness of the inferential analysis cannot be assessed from the registry record.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: iliac artery perforation (1.0%), chest pain (1.0%).

The registry lists serious adverse events and other adverse events separately. In the three groups corresponding to the posted 60 mg regimens, serious adverse events are recorded for 0 of 26 in the ticagrelor group, 0 of 27 in the aspirin plus clopidogrel group, and 0 of 28 in the aspirin plus ticagrelor group. Other adverse events are recorded for 7 of 26, 12 of 27, and 7 of 28, respectively. No deaths are recorded in those groups.

The safety listing also includes aspirin plus ticagrelor 90 mg and ticagrelor 90 mg monotherapy, with different numbers at risk. These entries should not be conflated with the listed 60 mg treatment groups. The registry names iliac artery perforation and chest pain among the top serious adverse-event terms, each with a reported 1.0%. The record does not provide further context for those terms in the posted summary.

These figures are counts recorded in the registry, not estimates of comparative risk adjusted for differences between groups. The adverse-event record does not report event timing, severity criteria beyond the serious/other classification, causal attribution, or statistical comparisons. Zero recorded serious events in a group does not establish that the risk is absent. The safety entries should be read as descriptive reports, with the limitations of the registry's available detail.

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

The results describe a laboratory measure of platelet response at a specific time: PRU measured by VerifyNow on day 10 before dosing. The group means and confidence intervals show the reported values for ticagrelor monotherapy, aspirin plus ticagrelor, and aspirin plus clopidogrel. They provide a snapshot of pharmacodynamic results under the regimens and endpoint timing recorded in the registry.

They do not, by themselves, establish whether the regimens differ on clinical outcomes, including ischemic events or bleeding. PRU is not a direct clinical event, and the registry's posted primary result does not supply a clinical-outcome comparison. Nor do the separate group confidence intervals establish the treatment contrast. A direct contrast requires a clearly defined comparison and its own estimate and uncertainty.

The posted non-inferiority analysis is not sufficient to conclude that non-inferiority was demonstrated. Its comparator and direction are unclear, and the margin and analytic method are not reported in the registry record. A confidence interval for a difference is interpretable for non-inferiority only in relation to a prespecified margin and a clearly specified contrast. The available entry should therefore be treated as a reported analysis with important interpretive details missing, rather than as a conclusive answer to the primary question.

The results also do not establish that an aspirin-free approach is appropriate for a particular person or for a broader patient population. The registry describes a study of patients with type 2 diabetes mellitus and coronary artery disease, but does not report enough eligibility or analysis-population details to define the reach of the result. The findings should be kept within the scope of the measured endpoint and the information recorded.

In short, the posted data support a descriptive account of PRU values and adverse-event counts in the listed groups. They do not settle the clinical implications of those values or resolve the stated non-inferiority question without the missing comparison and design details.

14. Why This Trial Matters Statistically

This trial is statistically interesting because its primary endpoint is a continuous pharmacodynamic measure recorded at a defined point in the dosing cycle. That makes the treatment contrast dependent not only on which regimens are compared, but also on the timing and measurement method. The registry specifies day 10 before dosing and describes the VerifyNow assay, giving important context for interpreting the group means.

It also illustrates why descriptive summaries and inferential comparisons are not interchangeable. The registry gives means and confidence intervals for three groups, but a primary treatment question requires a direct comparison with a clear estimate and uncertainty. The separate non-inferiority entry has a numerical estimate and interval, yet the contrast and non-inferiority margin are not reported. Those omissions limit the statistical conclusion even though numerical results are available.

Non-inferiority questions require particular care. The interpretation depends on a prespecified margin, a defined direction, and an analysis plan that makes clear which participants and measurements are included. The registry does not report those details. This makes the record a useful example of how a result can be numerically specific while still being difficult to interpret as a formal non-inferiority conclusion.

The record also distinguishes pharmacodynamic evidence from clinical outcomes. PRU measures an assay response; it is not itself a measure of ischemic harm or bleeding. Keeping that distinction clear prevents a laboratory comparison from being overstated as a clinical-effect comparison. The posted results are informative within their endpoint, but the statistical and clinical questions are not identical.

15. 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 principal limitation for interpreting the primary result is incomplete reporting of the sponsor's non-inferiority analysis. The registry gives a final-values mean difference of 7 and a 95% confidence interval from -23 to 38, but the analysis entry does not make the comparison clear. The non-inferiority margin, direction of the contrast, statistical method, and p-value are not reported in the registry record. Thus the result cannot be verified as an analysis of the named primary comparison or judged against a stated margin.

The registry reports group means and confidence intervals but not a direct estimate and confidence interval for the primary contrast in a clearly identifiable form. The group-level summaries cannot substitute for that comparison. The posted analysis also does not state the analysis population or describe missing-data handling, adherence, or protocol deviations. The endpoint group counts are not reconciled with the recorded enrollment.

The study is listed as randomized, parallel, and unmasked, but details of sequence generation, allocation concealment, and the reasons for the masking approach are not reported. Eligibility criteria and treatment duration beyond the endpoint timing are not available in the record summary. These limits make it difficult to assess the operational conduct of the study or how broadly the results may apply.

The primary endpoint is a pharmacodynamic laboratory measure at day 10 before dosing, not a clinical outcome. The registry summary does not provide a clinical-outcome comparison alongside the posted PRU results. Safety data are descriptive and include additional 90 mg groups, so those entries should not be confused with the three 60 mg regimens relevant to the primary endpoint. Finally, the registry's sample-size justification, interim-analysis plan, and full statistical analysis plan are not reported. These gaps constrain both the formal inference and the scope of any interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Ticagrelor With and Without Aspirin in Patients With Diabetes Mellitus — NCT04484259.
• Registry record last updated 2025-03-30; status last verified 2025-03.
• Results first posted 2025-03-30.
• 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.

19. Record Summary

NCT04484259 is a completed, randomized, parallel-group, unmasked Phase 4 study sponsored by the University of Florida. The registry records enrollment of 105 and identifies patients with type 2 diabetes mellitus and coronary artery disease. The study compares ticagrelor 60 mg twice daily alone, aspirin 81 mg once daily plus ticagrelor 60 mg twice daily, and aspirin 81 mg once daily plus clopidogrel 75 mg once daily.

The primary endpoint is mean PRU measured by VerifyNow on day 10 before dosing. The registry posts group means and 95% confidence intervals, along with a non-inferiority analysis whose contrast and margin are not clear from the record. Statistical methods, analysis populations, missing-data handling, and the trial's sample-size justification are not reported in the registry record. The posted results describe pharmacodynamic measurements and adverse-event counts; they do not, on their own, establish clinical effects or a fully interpretable non-inferiority conclusion.