Antiplatelet Effects of Evolocumab in Patients With Peripheral Arterial Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Antiplatelet Effects of Evolocumab in Patients With Peripheral Arterial Disease (NCT03247972), a registered phase not stated study. The primary outcome is Difference Between ADP-induced % Maximum Platelet Aggregation Between V2 (After 8 Weeks of HD Statin Therapy) and V5 (8 Weeks of Continued HD Statin Therapy + Evolocumab).

2. Clinical Question

The question is about a laboratory measure of platelet aggregation, rather than a clinical event such as a heart attack, stroke, limb event, or death. The primary endpoint is the mean difference in 5uM ADP-induced percentage maximum platelet aggregation from V2 to V5. The registry record names other platelet aggregation and activation measures as secondary outcomes, including collagen-induced aggregation, SFFLRN-induced aggregation, activated P-selectin-positive platelets, and TEG MAKH.

The treatment sequence is important for interpretation. The primary comparison follows a period of high-dose statin therapy and then a period of continued high-dose statin therapy with evolocumab. It is not described as a randomized comparison between people assigned to receive evolocumab and people assigned to remain on statin alone. Changes over time could therefore reflect more than the addition of evolocumab. The registry record does not report numerical endpoint results, estimates of variability, or an analysis testing the primary question.

3. Trial Design

The study is registered as NCT03247972 and is titled Antiplatelet Effects of Evolocumab in Patients With Peripheral Arterial Disease. Inova Health Care Services is listed as the sponsor. The registry record reports enrollment of 30 and a status of terminated. It lists a start date of 2017-08-11 and a primary completion date of 2019-09-01. The reason for termination is not reported in the registry record.

The planned assessment sequence included platelet activation and aggregation measures, along with biomarkers associated with platelet activation, oxidative stress, and inflammation. The brief description refers to measurement before initiation of study high-dose statin therapy, after 8 weeks of high-dose statin therapy, and 24 hours and 8 weeks after high-dose statin therapy plus evolocumab. The primary endpoint focuses specifically on the change from V2, after 8 weeks of high-dose statin therapy, to V5, after 8 weeks of continued high-dose statin therapy plus evolocumab.

The record names a high-dose statin period and a high-dose statin plus evolocumab period. It does not state that participants were randomly allocated to those periods or arms. The registry record explicitly cautions that the arms are not a like-for-like control comparison and that allocation is not stated. Accordingly, the comparison should be read as a change across treatment periods, not as a randomized estimate of the isolated effect of adding evolocumab.

Five outcome measures are listed, comprising the primary outcome and secondary measures. The record lists no analysis entries. It does not report how treatment was assigned, whether all enrolled participants completed each assessment, or what analysis populations were used. These design and reporting details limit the conclusions that can be drawn from the record, especially because the primary endpoint's numerical findings are absent.

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.

High Dose Statin Run-In Period (8 Weeks)

Reasons for not completing this period:

High Dose Statins + Evolocumab (8 Weeks)

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 Difference Between ADP-induced % Maximum Platelet Aggregation Between V2 (After 8 Weeks of HD Statin Therapy) and V5 (8 Weeks of Continued HD Statin Therapy + Evolocumab), measured over Change from week 8 (V2) to week 16 (V5).

The primary endpoint is the mean difference in ADP-induced percentage maximum platelet aggregation between V2 and V5. V2 is defined as the visit after 8 weeks of high-dose statin therapy; V5 is defined as the visit after 8 weeks of continued high-dose statin therapy plus evolocumab. The registry describes the measure as 5uM ADP-induced % maximum platelet aggregation and gives the unit as % maximum aggregation.

Platelet aggregation is a laboratory measure of how platelets respond to a stimulus. ADP is the stimulus named for this endpoint. The maximum aggregation measure represents the greatest aggregation recorded during the assay, expressed as a percentage. As general statistical context, a mean summarizes the average measured value across the observations included in an analysis, while the standard deviation describes how much individual measurements vary around that average. These definitions do not establish what happened in this study.

A change in this assay can be used to characterize a biological response over the specified treatment periods. It is a surrogate laboratory outcome, not a direct measure of a clinical event or a patient's symptoms. The registry record does not report the observed mean at either visit, the mean difference, a standard deviation, or an inferential result. It therefore does not establish the direction, size, or precision of the observed change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies the primary measure as a mean difference in a continuous outcome and names the standard deviation as the dispersion measure. The primary outcome is the change in ADP-induced percentage maximum platelet aggregation from V2 to V5. No numerical estimate or analysis result is reported, so the statistical concepts below explain how such summaries are generally interpreted rather than describing an analysis result from this study.

What does a mean difference describe?

In general, a mean difference expresses the change between two averages on the outcome's measurement scale. For a repeated assessment, it can summarize the average change between the specified visits among the observations included in the analysis. Its sign indicates direction according to the subtraction convention used by the analysis. The registry record calls the outcome a mean difference but does not state a numerical result or describe the exact calculation convention. Without the estimate, the direction and size of the change cannot be determined.

The mean is sensitive to the values of all observations included in its calculation. It can therefore be affected by unusually high or low measurements. A mean change also does not show whether every participant changed in the same direction. Some participants could have changes unlike the average, and the registry record does not report individual-level patterns or a distribution of changes.

What does the standard deviation add?

As general statistical context, the standard deviation describes the spread of observations around their mean. It is not the same as the uncertainty in the estimated mean. Uncertainty in a mean or mean difference also depends on how many observations contribute and on the analysis design. The record specifies standard deviation as the dispersion measure for the primary outcome but gives no standard deviation value. It also does not describe whether the reported dispersion would apply to visit measurements, participant-level changes, or another summary.

For repeated measurements, a paired analysis can account for the fact that observations from the same participant are related. An analysis that treats the two measurements as unrelated may not use that within-participant relationship appropriately. This is a general distinction; the registry record does not report the statistical test or model used, or whether the primary analysis treated the measurements as paired.

How should confidence intervals and p-values be read?

In general, a confidence interval gives a range of values compatible with the data and the method's assumptions, and communicates uncertainty about an estimated effect. Its width reflects precision: a narrower interval indicates greater precision under those assumptions. A p-value summarizes how unusual the observed data would be under a specified null hypothesis and model. Neither statistic alone establishes clinical importance, and neither replaces the estimated effect itself. The registry record does not report a confidence interval or p-value for the primary endpoint, so precision and statistical evidence cannot be assessed from the posted results.

Why does the treatment sequence matter?

The primary contrast is between a visit after high-dose statin therapy and a later visit after continued high-dose statin therapy plus evolocumab. As a general matter, a before-and-after contrast can describe change over time, but time-related influences and other changes occurring during the interval can also contribute. Random allocation and an appropriate concurrent control can help address some alternative explanations. The registry record does not describe random allocation and specifically warns that the listed arms are not a like-for-like control comparison. An unadjusted change across visits should therefore not be interpreted as a randomized treatment effect.

What does over-dispersion mean in general?

Over-dispersion occurs when observed variability is greater than a statistical model assumes. It is particularly relevant to some count outcomes, where a simple model can understate uncertainty if observations vary more than expected. The primary endpoint is continuous, and the record names a mean and standard deviation. It does not report a count model or an over-dispersion assessment. The general concept does not imply that over-dispersion occurred in this study.

How do planning calculations differ from observed results?

Sample-size illustrations are planning exercises, not findings from participants and not observed power. In general, such illustrations depend on assumptions about the target effect, variability, significance level, allocation, and statistical method. The record's stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect expressed as a fraction of the observed effect. Those assumptions do not establish that the original study used them to plan enrollment. The registry record does not report the trial's own sample-size justification or design calculations. No planning estimate should be read as an observed outcome or as evidence that the study did or did not have adequate power.

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("Patients With Peripheral Artery Disease Receiving ")
n   <- c(24)
m   <- c(0.71)
sp  <- c(10.8)
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  Patients With Peripheral Artery Disease Receiving   24  0.710  10.800  -3.850  5.270

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists five outcome measures: the primary ADP-induced aggregation measure and secondary measures concerning collagen-induced aggregation, SFFLRN-induced aggregation, activated P-selectin-positive platelets, and TEG MAKH. When a study evaluates multiple outcomes or multiple comparisons, the chance of at least one apparently unusual result can increase if no adjustment or prespecified testing strategy is used. As general statistical context, multiplicity procedures can control specified error rates, but they may also affect the precision or interpretation of individual tests. The registry record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or an approach to interpreting secondary analyses.

The registry lists no analysis entries and gives no numerical outcome findings. It does not report whether the primary outcome was analyzed according to a prespecified plan, whether secondary outcomes were treated as exploratory, or whether there were interim analyses. Those details are not reported in the registry record; their absence from the record does not establish what procedures were or were not carried out outside it.

Missing-data methods are not reported in the registry record. The number enrolled is listed as 30, but the record does not state how many participants had measurements at V2 and V5, whether any observations were missing, or how missing measurements were handled. It also does not report whether analyses used complete cases, imputation, or another approach. No analysis population, such as an intention-to-treat or per-protocol population, is specified. These omissions matter because the participants and measurements included in an analysis determine what population the estimated change describes.

The registry record also does not report a statistical analysis plan, model specification, or rules for excluding measurements. Without these details and the endpoint results, readers cannot assess how multiplicity, missing observations, or analysis-population choices affected the study's estimates.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiac intervention (11.5%).

The registry record lists adverse-event figures for the high-dose statin period and the high-dose statin plus evolocumab period. For high-dose statins, 30 participants are listed as at risk for serious adverse events and 0 as affected; the corresponding figures for other adverse events are 30 at risk and 1 affected. For high-dose statins plus evolocumab, 26 are listed as at risk for serious adverse events and 3 as affected; the figures for other adverse events are 26 at risk and 5 affected. Deaths are listed as 0 in each period. The most frequent serious adverse-event term is reported as cardiac intervention, at 11.5%.

These figures should be read as registry counts for the listed periods, not as a randomized comparison of safety. The record cautions that the arms are not a like-for-like control comparison and does not state allocation. The numbers at risk differ between periods, and the record does not explain why. The figures alone cannot establish that a treatment caused an event, or support a direct comparison of event rates.

The registry record does not provide further detail about event timing, duration, severity criteria, relatedness assessments, or the specific definition used for the non-serious category. The 11.5% figure is reported for the leading serious-event term, but its context and adjudication are not described. Adverse-event entries are descriptive registry information and should not be treated as a causal safety estimate.

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

The record establishes that a study was registered to examine platelet measures in people with PAD during high-dose statin therapy and after evolocumab was added. It identifies ADP-induced percentage maximum platelet aggregation as the primary outcome and defines a comparison from V2 to V5. It also lists secondary platelet-related measures and adverse-event summaries. These elements describe the research question and the information recorded about the study.

The record does not report the numerical result for the primary endpoint or for the secondary outcomes. It therefore cannot show whether platelet aggregation changed, in which direction it changed, how large the change was, or how precise an estimate might be. A stated endpoint is not itself a finding. Likewise, the study's enrollment figure and status do not substitute for participant-level outcome data or an analysis.

Even if a change between V2 and V5 were reported, the sequence would need to be interpreted in light of the design. The record does not state that allocation was randomized and cautions that the arms are not a like-for-like control comparison. A change over time during continued statin therapy and the addition of evolocumab would not, on its own, separate the effect of evolocumab from other changes over the same period.

The endpoint is a laboratory measure, not a clinical endpoint. As a general principle, a biological measurement can be useful for characterizing a response, but it does not by itself establish a change in clinical outcomes. The record does not report clinical outcome results for the primary question. Nor does it report statistical uncertainty, an analysis population, missing-data handling, or multiplicity procedures that would help evaluate the strength and robustness of any estimate.

The safety entries should also be interpreted descriptively. Their period-specific counts are not a randomized comparison, and they do not by themselves establish causation. In sum, the registry record identifies what investigators planned to measure and gives limited enrollment, status, and safety information; it does not provide the endpoint results needed to judge the primary statistical question.

14. Why This Trial Matters Statistically

This trial is statistically relevant because its question concerns change in a continuous biological measure across treatment periods. That makes the definition of the contrast central: the primary endpoint compares V2, after 8 weeks of high-dose statin therapy, with V5, after 8 weeks of continued high-dose statin therapy plus evolocumab. Naming the visits and measure helps clarify what an estimate would represent, while the absence of the estimate makes clear that the registered question cannot be answered from the posted results alone.

The record also highlights why study design affects interpretation. A sequential change can describe what was observed over time, but without a stated randomized allocation and a like-for-like control comparison, it does not isolate a treatment effect. This distinction is important when readers encounter a numerical change in a laboratory marker: a measured change and a causal effect are not interchangeable statistical claims.

Another statistical issue is the range of outcomes. The registry lists several platelet measures in addition to the primary endpoint. Multiple outcomes can provide a broader description of biological response, but they also raise questions about which analyses were prespecified and how multiplicity was handled. Those analysis details are not reported in the registry record.

Finally, the record illustrates that enrollment, status, and adverse-event counts are not substitutes for outcome reporting. Without the primary estimate, its variability, an uncertainty interval, and details of the analysis population and missing-data approach, readers cannot assess precision or robustness. The statistical value of a clinical trial report depends not only on defining a question, but also on reporting the estimates and methods needed to interpret the 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.

Several limitations specific to this record constrain interpretation. The study status is listed as terminated, but the reason for termination is not reported in the registry record. The record lists enrollment of 30, but does not report how many participants contributed measurements to the primary endpoint at both V2 and V5. The endpoint's numerical result, standard deviation, confidence interval, and p-value are not reported, and no analysis entries are listed.

The registry describes a sequence of high-dose statin therapy followed by continued high-dose statin therapy plus evolocumab. Allocation is not stated, and the record explicitly warns that the arms are not a like-for-like control comparison. The schedule therefore does not support treating a period-to-period difference as an isolated, randomized estimate of the effect of evolocumab.

The record does not report a full statistical analysis plan, the test or model used, the analysis population, missing-data handling, or multiplicity procedures. It also does not state whether all listed secondary outcomes were analyzed or how they would be interpreted in relation to the primary endpoint. The registry description refers to assessments at baseline, after 8 weeks of statins, and 24 hours and 8 weeks after combination therapy, but the primary outcome is defined for V2 to V5; results for the other planned time points are not reported.

The brief eligibility description refers to adults with PAD, and the arm description begins to list qualifying PAD histories, but the full eligibility details are not reported in the registry record. Safety entries give counts for the named periods but do not explain the unequal numbers at risk or provide additional event context. These limitations concern what the record reports; they do not establish what information may exist outside the registry.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Antiplatelet Effects of Evolocumab in Patients With Peripheral Arterial Disease — NCT03247972.
• Registry record last updated 2024-02-16; status last verified 2023-06.
• Results first posted 2024-02-16.
• 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

NCT03247972 is a study of platelet measures in adults with peripheral arterial disease receiving high-dose statin therapy and evolocumab. Inova Health Care Services is listed as sponsor. The record reports enrollment of 30, status as terminated, a start date of 2017-08-11, and a primary completion date of 2019-09-01. The reason for termination is not reported in the registry record.

The primary outcome is the mean difference in 5uM ADP-induced percentage maximum platelet aggregation from V2, after 8 weeks of high-dose statin therapy, to V5, after 8 weeks of continued high-dose statin therapy plus evolocumab. Four secondary outcomes are listed. The record does not report numerical results or analysis entries for these outcomes.

The listed treatment periods are not a randomized, like-for-like control comparison, and allocation is not stated. The record includes adverse-event counts but does not establish causation. Missing-data handling, analysis populations, multiplicity procedures, and the statistical analysis plan are not reported in the registry record.