COronary and MICrocirculatory Measurements in Patients With Aortic Valve Stenosis.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for COronary and MICrocirculatory Measurements in Patients With Aortic Valve Stenosis. (NCT04420325), a registered phase not stated study. The primary outcome is FFR 6 Months After SAVR/TAVI..

2. Clinical Question

Fractional flow reserve, or FFR, is described as distal coronary pressure divided by proximal coronary pressure. The record says FFR ranges from 0.0-1.0 and identifies 0.80 as the threshold for hemodynamic significance. Resting full-cycle ratio, or RFR, is considered alongside FFR in the planned assessment of ischemia against SPECT. These are study questions, not posted findings: the registry does not report whether the measures changed or how well they agreed with SPECT.

3. Trial Design

The registry identifies the study as completed, with enrollment of 116. The recorded study start is 2020-06-01, and primary completion is 2024-04-01. The sponsor is Universitaire Ziekenhuizen KU Leuven. The title is COronary and MICrocirculatory Measurements in Patients With Aortic Valve Stenosis; the official title identifies it as the COMIC AS Study.

The study summary describes prospective inclusion of 100 consecutive people with aortic stenosis and intermediate coronary artery disease. That planned inclusion description is distinct from the registry's reported enrollment of 116. The registry record does not explain the difference or report how many participants completed each assessment. It also does not report participant flow or the number included in the primary endpoint analysis.

The planned assessments were intracoronary hemodynamic measurements before aortic valve replacement and at 6 months afterward. An immediate assessment was described after valve replacement if transcatheter aortic valve replacement was chosen. Pre-procedure SPECT was planned, and the summary describes comparing FFR and RFR against SPECT as indicators of ischemia. Secondary outcomes listed in the record concern the index of microcirculatory resistance at 6 months after surgical or transcatheter intervention, and FFR versus RFR for determining ischemia.

This is not described as a randomized comparison. Allocation is not stated, and the registry record warns that arms are not a like-for-like control comparison. It does not report a detailed protocol, the distribution of procedure types, or a full statistical analysis plan. The outcome descriptions establish what was intended to be assessed; they do not establish that every planned assessment was completed or analyzed.

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

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: Entire study population

6. Primary Endpoint

The registry lists the primary outcome as FFR 6 Months After SAVR/TAVI., measured over 6 months.

The primary endpoint is FFR 6 months after surgical or transcatheter aortic valve replacement, expressed as a mean with standard deviation. The study description frames the endpoint as a change in FFR after valve intervention. FFR is the ratio of distal coronary pressure to proximal coronary pressure, with a stated range of 0.0-1.0. The registry describes lower FFR as indicating a more severe lesion and identifies 0.80 as the threshold for hemodynamic significance.

FFR is used in this study because the investigators ask whether aortic stenosis and its treatment affect pressure-based assessment of coronary artery disease. The study summary notes that myocardial hypertrophic remodeling may interfere with coronary blood flow and influence FFR and nonhyperemic pressure ratios. Measuring FFR after valve replacement is therefore intended to address whether the measurement differs after treatment, when microvascular function is expected to have improved.

The endpoint description does not supply an observed mean, standard deviation, baseline value, change estimate, confidence interval, or p-value. Nor does it describe the precise analysis population or the method for handling participants without a 6-month measurement. The endpoint definition explains the clinical measurement and intended timing, but the registry record does not report the numerical result needed to judge the size or precision of any change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean and standard deviation describe?

The primary outcome is specified as a mean of a continuous measure with standard deviation. In general, a mean describes the central value of measurements in an analyzed group. A standard deviation describes how spread out individual measurements are around that mean. These quantities answer different questions: the mean summarizes the group, while the standard deviation describes variation among measurements. Neither quantity, on its own, gives the uncertainty around an estimated change.

Because the study question concerns change after valve replacement, interpretation would ordinarily require comparing measurements across time. Repeated measurements from the same participant are related: a participant's values may be more alike than values from different participants. In general, an analysis of change should account for that within-participant relationship. This is a statistical principle, not a statement about the method used in this study. The registry record does not report whether the primary analysis used paired changes, a model of repeated measurements, or another approach.

How should a change estimate be read?

A change estimate describes the direction and size of a difference between measurement times, according to the analysis's stated convention. Its sign is interpretable only when the subtraction order is clear. For FFR, the registry explains that a lower value indicates a more severe lesion and gives 0.80 as the threshold for hemodynamic significance. But a group average and a threshold do not by themselves show how many individual lesions fall on either side of that threshold. The record does not report individual-level distributions, threshold-crossing counts, or the primary change estimate.

In general, a confidence interval expresses uncertainty around an estimate under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval, while the interval's location conveys which values remain compatible with the data and method. A p-value, when reported, summarizes how compatible the data are with a specified null model; it does not measure clinical importance or the probability that a hypothesis is true. The registry record reports no confidence interval or p-value for the primary endpoint, so these concepts cannot be applied to a posted estimate.

What do the diagnostic comparisons address?

The study summary describes comparing FFR and RFR with SPECT for assessment of ischemia. In general, a diagnostic comparison asks how well an index classifies or corresponds to a reference assessment in the studied population. Measures of diagnostic accuracy depend on the definitions of a positive result, the reference standard, and the analysis population. The registry does not report the diagnostic accuracy results or the detailed definitions and methods needed to interpret such estimates. Therefore, the planned comparison does not establish that either index performed better.

The secondary outcome concerning IMR addresses microvascular function at 6 months after surgical or transcatheter intervention. The record also describes an acute change in FFR after transcatheter valve replacement in its study summary. These questions concern different measurements and time points from the primary six-month FFR endpoint. The registry record does not report numerical results or analysis details for these outcomes.

What can the planning assumptions tell readers?

The record describes a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such a calculation is a planning aid: it illustrates the participant count associated with a specified effect and assumptions. It is not an observed result and should not be described as observed power. The illustration is also not evidence that the study itself used those assumptions to plan enrollment. The registry's own sample-size justification is not reported in the registry record.

The record does not provide the numerical planning outputs or the effect fractions used in the illustration. It also cautions that the study is not a randomized comparison, that allocation is not stated, and that arms are not a like-for-like control comparison. Thus, hypothetical equal-arm planning assumptions should not be read as a description of the actual study design or as a basis for a causal treatment comparison.

Why does variation matter?

Variation among FFR measurements affects how precisely a group mean or mean change can be estimated. A standard deviation describes that measurement spread, while a confidence interval would describe uncertainty around the estimated group quantity. Those concepts are related but not interchangeable. The registry identifies standard deviation as the dispersion measure for the primary outcome, but posts no value. Without the observed distribution and analysis details, readers cannot assess whether individual measurements were tightly clustered or widely dispersed.

General statistical methods can clarify what information would be useful, but they cannot replace missing trial results. For this study, the registry record does not report the primary estimate, its uncertainty, the analysis model, the handling of missing measurements, or the detailed diagnostic methods. Accordingly, the study's questions and measurement definitions can be described, but its statistical findings cannot be reconstructed from the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Entire Study Population")
n   <- c(116)
m   <- c(-0.0279)
sp  <- c(0.0368)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Entire Study Population  116  -0.028  0.037  -0.035  -0.021

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary FFR outcome and two named secondary outcomes: IMR at 6 months after surgical or transcatheter valve intervention, and FFR versus RFR for determining ischemia. The study summary also describes an acute FFR change after transcatheter valve replacement and diagnostic comparison with SPECT. These multiple questions create the general issue of multiplicity: when several outcomes or tests are examined, the chance of at least one apparently notable result can rise unless the analysis plan addresses that issue.

The registry record does not report a multiplicity strategy, such as a hierarchy for interpreting outcomes or an adjustment to statistical testing. It does not report interim analyses or a detailed statistical analysis plan. The record lists 0 analyses, so no outcome analysis is posted there. This does not establish what analyses may have been conducted outside the registry record.

Missing-data methods and analysis populations are not reported in the registry record. In particular, the record does not say how participants without a 6-month FFR measurement would be handled, whether analyses would include all enrolled participants or a defined subset, or how unavailable measurements would affect secondary analyses. Enrollment of 116 should not be assumed to equal the number analyzed.

These gaps limit reproducibility and interpretation. Without a stated analysis population, missing-data approach, and multiplicity plan, readers cannot determine which participants contributed to each estimate or how the several planned questions were handled statistically. No adjustment or analysis method should be inferred from the outcome listings alone.

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 0% reporting threshold.

The registry reports 116 participants at risk in the entire study population. It records 0 serious adverse events, 0 other adverse events, and 0 deaths. These are the event figures posted in the registry record; they are not results for the primary FFR endpoint.

A recorded zero means that the registry reports no events in the relevant category for the stated group. It does not, by itself, establish that no events occurred outside the registry's definitions or reporting period. The record does not report the detailed definitions used for serious and other adverse events, the method of event collection, or the timing and duration of safety follow-up. It also does not give event counts by procedure type or by measurement time.

The reported number at risk is not necessarily the number with complete follow-up for every outcome. The registry does not report the safety analysis population beyond the group description, nor does it provide a detailed account of participants who may have had incomplete safety information. These figures should therefore be read as the registry's recorded counts, without extending them to unreported periods, groups, or definitions.

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

The study addresses a measurement problem in people with aortic stenosis and coronary artery disease: whether pressure-based coronary indices are affected by aortic stenosis and its treatment. Its primary endpoint is FFR at 6 months after aortic valve replacement, framed as a change from before intervention. The study summary also describes an immediate FFR assessment after transcatheter valve replacement, a comparison of FFR and RFR with SPECT, and assessment of microvascular function.

Those questions are clinically and statistically distinct. A change in mean FFR would describe a group-level difference over time. A diagnostic comparison with SPECT would address how an index relates to an assessment of ischemia. An IMR result would address a different aspect of microvascular function. Evidence for one question would not, by itself, answer the others. The registry record does not report results for any of these questions.

The record therefore supports description of the study's purpose and planned measurements, but not a conclusion about whether FFR changed, whether RFR or FFR aligned more closely with SPECT, or whether microvascular function changed. It gives the FFR definition and the 0.80 threshold, but does not report how observed measurements were distributed relative to that threshold. The threshold cannot substitute for an observed result.

The record's completed status and enrollment of 116 do not establish that the planned analyses were completed or that a particular finding was observed. No primary estimate, uncertainty interval, p-value, or analysis population is reported. The safety counts are also limited to the adverse-event entries recorded and do not answer the efficacy questions.

Accordingly, the appropriate interpretation is that the registry describes a prospective study question and outcome framework, while leaving the statistical findings unavailable in the registry record. Any stronger statement about the size, direction, precision, or clinical implications of an effect would require results not reported there.

14. Why This Trial Matters Statistically

This study matters statistically because it focuses on whether the measurement used to assess coronary disease may itself depend on the surrounding physiology. The study summary states that myocardial hypertrophic remodeling can interfere with coronary blood flow and may influence FFR and nonhyperemic pressure ratios. If measurement values differ before and after valve replacement, interpretation of a pressure index may depend on when it was obtained. This is the rationale for measuring coronary hemodynamics at multiple time points.

The design also brings together different kinds of evidence. FFR and RFR are pressure-based indices, SPECT is used as a comparison for ischemia assessment, and IMR is included as a measure of microvascular function. Statistical interpretation must keep these questions separate: a change over time, agreement with a reference assessment, and a measure of microvascular function are not interchangeable outcomes.

There is also an important design distinction. The registry does not describe a randomized control comparison; allocation is not stated, and arms are not like-for-like controls. The main question is described through measurements around valve replacement rather than a stated randomized contrast. That makes careful attention to time points, participant-level repeated measurements, and analysis populations important. The registry does not report how those details were handled.

The record's lack of posted analyses is itself consequential for interpretation. The outcome definitions and rationale show what the investigators intended to study, but without estimates and uncertainty, readers cannot assess whether the measurements changed or how precisely any change was estimated. The registry therefore illustrates the difference between a well-defined statistical question and a reported statistical answer.

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 main trial-specific limitation is that the registry record does not report the primary endpoint result. It provides no observed FFR mean, standard deviation, change estimate, confidence interval, or p-value. There are also no posted analyses for the secondary outcomes. The study's completed status does not fill this evidence gap.

The registry reports enrollment of 116, while the study summary describes planned prospective inclusion of 100 consecutive participants with aortic stenosis and intermediate coronary artery disease. The record does not explain the difference or state how many participants contributed to each outcome. It does not report participant characteristics, procedure-type counts, or completion of follow-up at 6 months. The generalizability of any result therefore cannot be assessed from the registry record.

The study summary describes an immediate post-procedure measurement only if transcatheter aortic valve replacement was chosen, alongside measurements before intervention and at 6 months. The registry does not report which participants received each procedure or how the different assessment schedules would be handled analytically. It also cautions that this is not a randomized comparison and that arms are not like-for-like controls, while allocation is not stated. Causal comparisons between procedure groups should not be inferred.

Important analysis details are not reported in the registry record, including the statistical model, analysis population, missing-data method, multiplicity approach, and interim-analysis plan. Diagnostic accuracy definitions and results for FFR and RFR versus SPECT are also absent. These limitations prevent assessment of precision, robustness, and the extent to which the planned measurements were completed.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: COronary and MICrocirculatory Measurements in Patients With Aortic Valve Stenosis. — NCT04420325.
• Registry record last updated 2025-09-05; status last verified 2025-06.
• Results first posted 2025-09-05.
• 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

The COMIC AS Study concerns coronary and microcirculatory measurements in people with aortic valve stenosis and coronary artery disease. The registry reports enrollment of 116 and a completed status. The study summary describes planned prospective inclusion of 100 consecutive participants with aortic stenosis and intermediate coronary artery disease.

The primary endpoint is FFR 6 months after surgical or transcatheter aortic valve replacement, expressed as a mean with standard deviation. Planned assessments include intracoronary measurements before intervention and at 6 months, with an immediate assessment after transcatheter intervention if chosen. Secondary questions concern IMR and FFR versus RFR for ischemia assessment, including comparison with SPECT.

The registry record reports 0 serious adverse events, 0 other adverse events, and 0 deaths among 116 participants at risk. It does not report the primary endpoint result, secondary outcome analyses, or detailed statistical methods. Thus, the record describes the study's questions and recorded safety counts but does not provide the results needed to evaluate its central statistical findings.