Comparison of a Rivaroxaban-based Strategy With an Antiplatelet-based Strategy Following Successful TAVR for the Prevention of Leaflet Thickening and Reduced Leaflet Motion as Evaluated by Four-dimensional, Volume-rendered Computed Tomography (4DCT): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparison of a Rivaroxaban-based Strategy With an Antiplatelet-based Strategy Following Successful TAVR for the Prevention of Leaflet Thickening and Reduced Leaflet Motion as Evaluated by Four-dimensional, Volume-rendered Computed Tomography (4DCT) (NCT02833948), a randomized phase 3 study. The primary outcome is Rate of Patients With at Least One Prosthetic Leaflet With >50% Motion Reduction as Assessed by Cardiac 4DCT-scan.

2. Clinical Question

The study addresses a specific imaging outcome after TAVR. It compares two treatment strategies rather than isolating the effect of one drug: both regimens include ASA during the initial 90 days, while the additional drug and subsequent monotherapy differ. The registry describes the rationale as uncertainty about the optimal blood-thinning therapy after TAVR and the possibility of leaflet thrombosis with reduced leaflet motion.

The primary question concerns a structural and motion finding on imaging. It is not a direct test of whether either strategy changes symptoms, neurological events, or survival. Those broader outcomes cannot be inferred from the primary endpoint alone.

3. Trial Design

This was a randomized, parallel-group phase 3 study with single masking. The registry lists enrollment as 231 and the study status as completed. The study began in 2016-05, with primary completion in 2018-12. The sponsor is ECRI bv. Further details about how randomization was performed, what single masking entailed, and the intended allocation ratio are not reported in the registry record.

Participants were assigned to ASA plus clopidogrel or rivaroxaban plus ASA. Each regimen used combination therapy for 90 days, followed by monotherapy: ASA alone in the ASA plus clopidogrel arm, and rivaroxaban alone in the rivaroxaban plus ASA arm. This means the randomized contrast represents the overall strategy, including both the combination phase and the subsequent monotherapy phase, rather than a comparison of one medication in isolation.

The primary endpoint was assessed at 3 months using cardiac 4DCT. The registry identifies the primary analysis population as intention-to-treat. The primary outcome counts were 11 participants among 101 in the ASA plus clopidogrel arm and 2 among 97 in the rivaroxaban plus ASA arm. Outcome-specific denominators differ for some secondary results, so those results should be interpreted using their own posted denominators rather than assuming that every endpoint has the same analysis population.

The registry lists a range of additional outcomes, including leaflet thickening, echocardiographic measures, and exploratory analyses relating leaflet abnormalities to death or thromboembolic events. Detailed protocol information, including the original design assumptions, is not reported in the registry record.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intention-to-treat (ITT) study population

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 Rate of Patients With at Least One Prosthetic Leaflet With >50% Motion Reduction as Assessed by Cardiac 4DCT-scan, measured over 3 months.

The primary endpoint is the rate of participants with at least one prosthetic leaflet showing more than 50% motion reduction on cardiac 4DCT at 3 months. The registry defines reduced systolic leaflet excursion in categories: normal, mildly reduced (<50%), moderate to severely reduced (>50%), and immobile. Motion reduction is considered significant when it is >50% or the leaflet is immobile.

The assessment uses a blood-pool inversion, volume-rendered cine reconstruction throughout the cardiac cycle to evaluate bioprosthetic leaflet motion. The endpoint is participant-based: a participant is counted if at least one prosthetic leaflet meets the threshold. It is therefore not the same measure as the rate of affected leaflets, which is listed separately among the secondary outcomes.

As a general statistical point, an imaging endpoint can capture a specific anatomical or functional feature at a defined assessment time. It does not, by itself, establish how that feature relates to symptoms or other clinical outcomes. The registry describes possible links between leaflet abnormalities and neurological events as background rationale, but the primary endpoint measures leaflet motion on imaging, not neurological events.

The endpoint is useful for making a focused comparison of the imaging finding between randomized strategies. Its interpretation depends on the stated threshold and assessment method; details of image-reading procedures, reader agreement, and handling of unreadable scans are not reported in the registry record.

7. Results Posted in the Registry

• Rivaroxaban + ASA: 2.1% (2/97) versus 10.9% (11/101) on control; risk difference -8.8 percentage points (95% CI -15.5 to -2.1), risk ratio 0.19 (0.04–0.83); unadjusted two-proportion z-test p = 0.012.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

The Rate of Patients With at Least One Prosthetic Leaflet With Thickening as Assessed by Cardiac 4DCT-scan

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Rivaroxaban + ASA: 12.4% (12/97) versus 32.4% (33/102) on control; risk difference -20.0 percentage points (95% CI -31.2 to -8.8), risk ratio 0.38 (0.21–0.70); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Rivaroxaban + ASA than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Aortic Transvalvular Mean Pressure Gradient (mmHg) as Determined by Transthoracic Echocardiography.

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Rivaroxaban + ASA: mean 10.00 versus 10.00 on control; difference 0.00 (95% CI -1.36 to 1.36), standardized effect d = 0.00; z-test p = 1.000.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Rivaroxaban + ASA and the control. The interval gives the range of effects that remain compatible with the data.

Effective Orifice Area (cm^2) as Determined by Transthoracic Echocardiography.

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Rivaroxaban + ASA: mean 1.80 versus 1.80 on control; difference 0.00 (95% CI -0.12 to 0.12), standardized effect d = 0.00; z-test p = 1.000.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Rivaroxaban + ASA and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes extend the assessment from the participant-level primary motion endpoint to leaflet thickening and echocardiographic measures. Among the arm summaries, the leaflet-thickening result follows a direction similar to the primary imaging contrast, while the reported group means for the hemodynamic measures do not show a separation. These outcomes address related but distinct features: leaflet thickening is an imaging finding, whereas pressure gradient and effective orifice area are echocardiographic measurements.

This overall pattern can add context, but it does not turn the primary result into evidence about every aspect of valve function or clinical outcome. A directionally similar imaging measure may support coherence across related endpoints, while a lack of separation in group means for other measures underscores that endpoints capture different phenomena. The secondary findings should therefore be interpreted outcome by outcome, with attention to their measurement scale and denominators.

The registry lists other secondary and exploratory questions, including associations involving leaflet abnormalities, death, and thromboembolic events. Detailed results for some listed outcomes are not reported in the registry record. Their presence in the list does not establish an observed relationship.

Secondary results generally carry less weight than the prespecified primary result when many outcomes are examined. Testing multiple outcomes increases the chance that at least one result may appear notable through random variation. The registry does not report a multiplicity adjustment for the secondary comparisons. Consequently, unadjusted secondary findings are best treated as supportive or exploratory rather than as independent confirmation of the primary result.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• The Rate of Prosthetic Leaflets With > 50% Motion Reduction as Assessed by Cardiac 4DCT-scan
• The Rate of Patients With at Least One Prosthetic Leaflet With Thickening as Assessed by Cardiac 4DCT-scan
• The Rate of Prosthetic Leaflets With Thickening as Assessed by Cardiac 4DCT-scan
• Aortic Transvalvular Mean Pressure Gradient (mmHg) as Determined by Transthoracic Echocardiography.
• Effective Orifice Area (cm^2) as Determined by Transthoracic Echocardiography.
• Death Assessed in the Main GALILEO Study and Analyzed in the GALILEO-4D Substudy With Regards to Occurence of the Leaflet Abnormalities (HALT) - as Exploratory Analysis.
• Death Assessed in the Main GALILEO Study and Analyzed in the GALILEO-4D Substudy With Regards to Occurence of the Leaflet Abnormalities (RLM)- as Exploratory Analysis.
• Thromboembolic Event Assessed in the Main GALILEO Study and Analyzed in the GALILEO-4D Substudy With Regards to Occurence of the Leaflet Abnormalities (HALT)- as Exploratory Analysis.

9. Statistical Interpretation

10. Statistical Methods Explained

What does the risk difference represent?

The risk difference is the event proportion in one arm minus the event proportion in the comparator arm. In this comparison, the contrast is rivaroxaban plus ASA against ASA plus clopidogrel. A negative estimate indicates that the observed proportion was lower in the rivaroxaban plus ASA arm. The posted estimate is -0.088. This is an absolute contrast in proportions, not a relative measure.

Absolute contrasts are often straightforward to interpret because they describe the difference between the two observed event proportions on the same scale. However, the estimate is still subject to sampling uncertainty. The interval from -0.155 to -0.021 indicates a range of values compatible with the analysis method and data; it does not show that the true difference is known exactly.

How should the p-values be read?

A p-value describes how unusual data at least as inconsistent with the null comparison would be if the null hypothesis and the test assumptions held. It is not the probability that the null hypothesis is true, and it is not a measure of the size or importance of an effect. The recalculated unadjusted p-value is 0.012. The registry reports a Fisher Exact analysis with p = 0.01. A p-value should be considered alongside the observed proportions and interval, not used as a stand-alone verdict.

Fisher Exact is a method for comparing categorical event counts. It calculates the probability of arrangements of the observed counts under a null model, conditional on the margins of the comparison. The registry identifies this as the reported primary analysis method. The recalculated comparison is described as an unadjusted recalculation from the posted summary statistics; it is not a replacement for the sponsor's analysis.

Why are relative measures also useful?

Relative measures express the event proportion in one group in relation to the other, while the risk difference expresses an absolute contrast. The posted risk ratio is 0.189, with an interval from 0.043 to 0.832; the posted odds ratio is 0.172, with an interval from 0.037 to 0.799. These measures use different scales and should not be confused with the absolute risk difference. Their interpretation also depends on the event being compared and the direction of the group contrast.

For binary outcomes, the risk ratio compares proportions directly. The odds ratio compares odds, which are the event odds relative to the non-event odds. When events are not common, the odds ratio can differ noticeably from the risk ratio. Neither relative measure conveys the absolute event burden on its own; the group counts and proportions remain important context.

What is the role of the analysis population?

The primary endpoint identifies the intention-to-treat study population. In general, intention-to-treat analysis compares participants according to their randomized assignment, regardless of later treatment changes, and helps preserve the benefits of randomization. The registry record does not provide details about how missing primary endpoint assessments, exclusions, or any deviations from assignment were handled. Therefore, the label alone does not resolve questions about which randomized participants contributed outcome data.

Denominators can vary across outcomes because an assessment may be available for different numbers of participants. For the primary endpoint, the posted denominators are 101 and 97. Secondary outcomes have their own denominators. Comparisons should use the outcome-specific counts and should not assume that every measure was observed for the same participants.

Why can over-dispersion matter in other trial outcomes?

As a general statistical concept, over-dispersion occurs when observed variability is greater than expected under a model's assumptions. It is relevant to some count outcomes and can make standard errors too small if ignored. The primary endpoint is binary at the participant level, and the posted primary comparison uses event counts. The registry does not report an over-dispersion parameter for this outcome. This general concept should not be read as evidence that over-dispersion affected the reported primary analysis.

For continuous outcomes, such as the echocardiographic measures listed as secondary endpoints, means and standard deviations describe the group summaries. A mean difference expresses the contrast on the outcome's measurement scale. These summaries do not replace an assessment of uncertainty or missing data, and the registry's displayed continuous outcome information should be interpreted separately from the binary primary endpoint.

What do the methods not establish?

Statistical significance does not establish clinical importance, and an interval does not account for every possible source of bias. Randomization helps support a causal comparison of assigned strategies, but the registry does not report enough detail to evaluate all operational aspects, such as image assessment procedures or treatment adherence. The analyses are also tied to the measured endpoint and follow-up time. They do not automatically answer questions about longer-term outcomes or outcomes that were not reported.

11. Confidence Intervals and Precision

The primary comparison is based on 11 events among 101 participants in the ASA plus clopidogrel arm and 2 among 97 in the rivaroxaban plus ASA arm. The posted risk-difference estimate is -0.088, with an interval from -0.155 to -0.021. The interval summarizes uncertainty around the estimated absolute difference under the comparison method. It does not guarantee that the underlying effect lies within those bounds, nor does it include uncertainty from every possible limitation in study conduct or outcome measurement.

Because the interval remains below zero, the estimated direction is not simply a point estimate in favor of either group with a broad range spanning zero. Even so, the interval covers a range of possible magnitudes. Readers should distinguish the direction of the contrast from how precisely its size is known. The registry does not state the confidence level for this interval, so the interval is described without assigning a percentage level.

The posted relative intervals are also broad: the risk ratio is 0.189 with an interval from 0.043 to 0.832, and the odds ratio is 0.172 with an interval from 0.037 to 0.799. These are relative scales and do not replace the absolute risk-difference interval. Comparing scales without noting their definitions can make the evidence seem more or less precise than it is.

Precision is shaped by the number of observed events as well as the group denominators. With sparse event counts, a small change in the observed counts can affect relative estimates substantially. This is a general property of binary-outcome analyses, not a separate finding about these participants. The posted estimate is informative about the observed contrast, while the interval makes clear that the effect magnitude remains uncertain.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed primary effect, not the original trial design. They give participants per arm, not total participants. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The assumed effect to detect is the stated fraction of the observed effect. The original trial's sample-size justification and design assumptions are not reported in the registry record.

For planning based on 100% of the observed effect, the illustration gives 121 participants per arm for 80% power and 162 participants per arm for 90% power. For planning based on 75% of the observed effect, it gives 250 participants per arm for 80% power and 334 participants per arm for 90% power. For planning based on 50% of the observed effect, it gives 638 participants per arm for 80% power and 853 participants per arm for 90% power.

In plain language, the 80% power column represents the planning sample size that would give an 80% chance of detecting the assumed effect under the stated model and assumptions if that effect were present. The 90% column uses a higher target chance of detection, and therefore calls for a larger planned sample size for the same assumed effect. Smaller assumed effects require more participants because they are harder to distinguish from random variation.

These figures are not observed power. They are illustrations calculated from the observed effect and depend on the stated assumptions; a different true effect, event rate, allocation, or analysis method could lead to different planning requirements. They should not be read as evidence that the completed trial was designed around these figures.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.109; treatment proportion p₁ = 0.021; average p̄ = 0.065.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.3481 = 0.6822.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.3424 = 0.2882.
4. n = (0.6822 + 0.2882)² / (-0.0883)² = 120.8, rounded up to 121 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.108910891089109                          # control proportion
p1 <- 0.0206185567010309                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2833948)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 121 (80% power), 162 (90% power)
 75% of observed effect: n per arm = 250 (80% power), 334 (90% power)
 50% of observed effect: n per arm = 638 (80% power), 853 (90% power)
power.prop.test: 120.8 
Simulated power at n = 121 per arm: 0.840 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports the sponsor's primary analysis as Fisher Exact, with p = 0.01 for the comparison of ASA plus clopidogrel with rivaroxaban plus ASA. The unadjusted recalculation from the posted summary statistics gives p = 0.012 and a risk difference of -0.088, with an interval from -0.155 to -0.021. The recalculated figures add an absolute-effect estimate and interval to the comparison of the posted event counts.

The reported p-value and recalculated p-value are close but are not identical. The registry record identifies the sponsor's test as Fisher Exact, whereas the recalculation is based on the posted summary statistics. The registry does not explain the numerical difference between the two p-values. No discrepancy is flagged for this result, and the sponsor's reported analysis remains the registered analysis to cite when describing what the sponsor reported.

The recalculation is unadjusted and should not be presented as a corrected or adjusted analysis. It is useful for interpreting the magnitude and uncertainty of the observed contrast, but it does not supersede the sponsor's stated method or address other design, missing-data, or multiplicity questions.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary endpoint and lists numerous secondary and exploratory outcomes. When multiple outcomes are tested, the chance of at least one apparently notable result can increase even if none of the underlying effects is real. Statistical procedures for multiplicity can control this problem, but they may also change how uncertainty is interpreted. Whether an adjustment was planned or applied is not reported in the registry record.

Accordingly, the primary outcome should remain the central confirmatory comparison, while secondary results should be interpreted more cautiously. The registry's reported primary Fisher Exact p-value and the unadjusted recalculated comparisons do not, by themselves, establish how the full family of outcomes was handled. A formal hierarchy, gatekeeping approach, or other prespecified multiplicity strategy is not reported in the registry record.

The primary endpoint is identified as intention-to-treat, but the registry record does not describe the handling of missing scans or other missing outcome data. The numbers of participants randomized and the endpoint-specific analysis denominators are not identical in every posted result. Without further information about missingness, exclusions, or imputation, it is not possible to determine whether missing outcomes could have influenced the estimates.

Details on whether outcome assessors were masked, how imaging disagreement was resolved, and how unreadable scans were treated are not reported in the registry record. The study is labeled single masked, but the identity of the masked parties and the operational procedure are not specified. These issues are relevant because image-based outcomes require measurement and classification decisions.

The record also does not report the full statistical analysis plan, interim analyses, or the trial's original sample-size justification. Their absence from the registry record should not be interpreted as evidence that such procedures were or were not used. It limits what can be concluded from the posted information about prespecification and the treatment of all analyses.

16. 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: major bleeding event (3.5%), thromboembolic event (3.5%).

The safety summaries use their own denominators: 116 participants at risk in the ASA plus clopidogrel group and 115 in the rivaroxaban plus ASA group. Serious adverse events affected 3 participants in the ASA plus clopidogrel group and 7 in the rivaroxaban plus ASA group. Other adverse events affected 17 and 16 participants, respectively. The posted death counts are 2 and 3, respectively.

The record also lists major bleeding event and thromboembolic event among the top serious adverse event terms, each at 3.5%. Those percentages are reported as terms and are not assigned to a specific treatment group in the information available. The registry record does not provide further detail about event severity definitions, timing, exposure-adjusted rates, or the relationship between these terms and the group-level serious adverse event counts.

These summaries are descriptive. They do not establish that one strategy is safer than the other, particularly without a prespecified comparative safety analysis, uncertainty estimates, and fuller details of event ascertainment. They should be read separately from the imaging efficacy endpoint and should not be used alone to make treatment decisions.

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

The posted primary data show fewer participants with the specified reduced-motion finding in the rivaroxaban plus ASA arm than in the ASA plus clopidogrel arm at 3 months. The unadjusted absolute contrast is -0.088, with an interval from -0.155 to -0.021. This describes the observed comparison for a cardiac 4DCT endpoint in this randomized substudy.

The finding does not establish that rivaroxaban prevents clinical events, improves survival, or changes symptoms. Leaflet motion on imaging is not the same outcome as death, stroke, or other patient-important events. The registry lists some exploratory analyses relating abnormalities to clinical outcomes, but the primary result alone cannot answer those questions.

The comparison is between two complete treatment strategies. Both include ASA with another antithrombotic drug for 90 days, followed by different monotherapies. Therefore, the result cannot be attributed to rivaroxaban alone, to clopidogrel alone, or to one treatment period separately. It applies to the strategies as described in the registry.

The result also pertains to the assessment at 3 months. Longer-term persistence of the imaging finding and longer-term clinical consequences are not established by this endpoint. Information about follow-up beyond the stated primary timeframe is not reported in the registry record.

Finally, the result should be interpreted with the uncertainty in the estimate and the limits of the posted record in mind. Missing scan handling, adherence, image-reading procedures, and multiplicity methods are not reported in the registry record. The data describe a difference in a defined imaging outcome; they do not, by themselves, establish an overall balance of benefits and harms.

18. Why This Trial Matters Statistically

This study illustrates why an endpoint's level of measurement matters. The primary outcome is counted at the participant level, with a participant classified as having the finding if at least one prosthetic leaflet meets the motion-reduction threshold. A separate secondary outcome counts affected leaflets. Those two denominators and interpretations are not interchangeable: a person-level rate answers whether participants had the finding, while a leaflet-level rate concerns the affected prosthetic leaflets.

The example also shows the value of reporting absolute and relative contrasts together. The risk difference describes the absolute gap in observed proportions, while the risk ratio and odds ratio use relative scales. Those measures answer related but different questions. A reader who sees only a p-value can miss both the magnitude of the observed contrast and the range of uncertainty around it.

Endpoint selection matters as well. An imaging outcome can be relevant to understanding valve leaflet behavior after TAVR, but it is not automatically a substitute for clinical outcomes. Separating the imaging result from patient-important endpoints prevents a statistical finding from being interpreted more broadly than the data support.

Finally, the trial is a reminder that a positive primary comparison and uncertain secondary or safety findings can coexist. Multiplicity, outcome-specific denominators, missing-data handling, and the distinction between a randomized strategy and a single drug all influence how findings should be weighed. Transparent reporting of these features is central to a careful statistical reading.

19. 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 does not provide the full eligibility criteria, the details of sequence generation or allocation concealment, or the identity of the parties masked under the single-masking design. These omissions limit assessment of how randomization and masking were implemented. The primary endpoint is imaging-based, but image-reader training, central review procedures, reader agreement, and handling of unreadable scans are not reported in the registry record.

Although the primary analysis population is identified as intention-to-treat, the registry record does not explain how missing primary scans or other missing data were handled. It also does not provide treatment adherence, crossover, discontinuation, or protocol-deviation details. These factors could affect how closely the observed analysis represents the assigned treatment strategies.

The posted primary result concerns one endpoint at 3 months. Long-term outcomes and the clinical implications of the imaging finding are not established by this result. Some listed secondary and exploratory outcomes do not have detailed results reported in the registry record. The registry also does not report whether multiplicity adjustments were used, or the original trial sample-size justification and statistical analysis plan.

Safety information is summarized with event counts and selected terms, but the record does not report a full comparative safety analysis with uncertainty estimates or additional event-ascertainment details. These limitations do not negate the posted primary comparison; they define what can be assessed from the registry record and what remains uncertain.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Comparison of a Rivaroxaban-based Strategy With an Antiplatelet-based Strategy Following Successful TAVR for the Prevention of Leaflet Thickening and Reduced Leaflet Motion as Evaluated by Four-dimensional, Volume-rendered Computed Tomography (4DCT) — NCT02833948.
• Registry record last updated 2020-01-18; status last verified 2020-01.
• Results first posted 2020-01-18.
• 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.

23. Record Summary

NCT02833948 is a completed randomized, parallel-group phase 3 substudy comparing rivaroxaban plus ASA with ASA plus clopidogrel after successful TAVR. The listed enrollment is 231, and the primary outcome is the participant rate of at least one prosthetic leaflet with more than 50% motion reduction or immobility on cardiac 4DCT at 3 months.

The primary event counts were 11 among 101 participants in the ASA plus clopidogrel arm and 2 among 97 in the rivaroxaban plus ASA arm. The unadjusted risk-difference estimate was -0.088, with an interval from -0.155 to -0.021; the registry reports Fisher Exact p = 0.01. The registry record provides secondary imaging and echocardiographic outcomes, but multiplicity methods, missing-data handling, and several design details are not reported in the registry record.