STrategic Reperfusion in Elderly Patients Early After Myocardial Infarction: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for STrategic Reperfusion in Elderly Patients Early After Myocardial Infarction (NCT02777580), a randomized phase 4 study. The primary outcome is Successful Reperfusion.

2. Clinical Question

The study frames the comparison as one between two reperfusion strategies rather than a comparison of a single drug with a procedure. The pharmaco-invasive strategy combines early fibrinolytic treatment and antiplatelet and antithrombin therapy with planned angiography or rescue intervention. The comparator is primary PCI with accompanying treatment according to local standards. The posted primary outcome concerns the ECG change after angiography or PCI, not a longer-term clinical event.

The registry summary describes the intended population and timing, but does not report detailed eligibility criteria, such as exclusions or the precise clinical criteria used to identify eligible patients. It also does not report a more detailed definition of the local standards used in the comparator group. Those omissions limit how specifically the intended treatment contrast can be characterized from the registry record alone.

3. Trial Design

The registry describes a randomized, open-label, parallel-group phase 4 trial. Randomization means assignment to the strategies was intended to be determined by chance; open-label means masking was not used. The posted record lists KU Leuven as sponsor and gives the status as completed. Enrollment is listed as 609. The registry dates are 2017-08-01 for study start and 2022-10-13 for primary completion.

The intervention was a treatment pathway: half-dose tenecteplase, a 300 mg clopidogrel loading dose, aspirin, and antithrombin therapy, followed by coronary angiography within 6-24 hours or rescue coronary intervention as required. The comparator was primary PCI with a P2Y12 antagonist and antithrombin treatment according to local standards. This means the study compares strategies that include multiple treatment components and different timing or pathways, not isolated components.

The posted primary-outcome group counts are 358.0 for the pharmaco-invasive strategy and 190.0 for standard primary PCI. The registry separately lists serious-adverse-event risk groups of 401 and 203. These different denominators are both part of the record; the reason for the differences is not reported in the registry record. The enrollment figure and outcome denominators should therefore not be treated as interchangeable.

The registry record does not report the randomization procedure, allocation concealment, site count, trial locations, or details of adherence and crossover. It also does not report a detailed protocol or the original design assumptions. The trial's status and dates describe its registry history, but do not supply those methodological 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.

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.

6. Primary Endpoint

The registry lists the primary outcome as Successful Reperfusion, measured over 30 min post angiogram/PCI.

The primary endpoint is a count of participants meeting the registry's definition of successful reperfusion. Success was defined as worst-lead ST-segment elevation resolution ≥ 50% at 30 min post angiogram/PCI. The measurement is therefore based on an ECG change after the relevant angiography or PCI, rather than on a later event such as survival or reinfarction.

In general, ST-segment resolution is used as an indicator of change in the ECG pattern associated with acute myocardial infarction after reperfusion treatment. A threshold-based endpoint turns a continuous ECG change into a binary classification: a participant either meets the stated threshold or does not. The record's definition specifies the worst lead and the threshold, as well as the time point after the procedure. Those details matter because a different lead-selection rule, threshold, or measurement time could define a different endpoint.

The endpoint captures an early physiologic response. It does not by itself describe all aspects of recovery, later clinical outcomes, or treatment-related harms. The registry reports participants meeting the endpoint as counts for the two groups. It does not report the measurement procedures, who assessed the ECGs, or whether endpoint assessment was independently adjudicated. Because the trial was unmasked, the record does not establish that assessment was blinded.

7. Results Posted in the Registry

• Pharmaco-invasive Strategy: 85.2% (305/358) versus 78.4% (149/190) on control; risk difference 6.8 percentage points (95% CI -0.1 to 13.7), risk ratio 1.09 (1.00–1.18); unadjusted two-proportion z-test p = 0.045.

8. Statistical Interpretation

9. Statistical Methods Explained

The reported outcome is binary: each participant either met the specified ST-segment resolution threshold or did not. The posted group results are counts of participants meeting the endpoint and the group sizes used for that outcome. A comparison of binary outcomes can be expressed as a difference in proportions, a ratio of proportions, or a ratio of odds. These measures answer related but distinct questions, so their numerical values need not be similar.

What does the risk difference express?

The risk difference subtracts the outcome proportion in one group from the outcome proportion in the other, following the comparison's stated order. Its posted estimate is 0.068, and its interval runs from -0.001 to 0.137. Positive values indicate a greater endpoint proportion in the pharmaco-invasive group under that ordering; negative values indicate a greater proportion in the standard primary PCI group. A value of zero represents no difference in the proportions. The interval crosses zero, so its range includes no difference as well as values on either side.

A confidence interval, in general, conveys uncertainty about an estimate under a statistical procedure and its assumptions. A narrower interval indicates greater precision than a wider interval on the same scale. The registry does not report the confidence level for the listed intervals. It is therefore appropriate to discuss their bounds, but not to attach an unreported confidence level.

How do the ratio measures differ?

The risk ratio compares the endpoint proportions directly. The posted estimate is 1.086, with an interval from 0.997 to 1.184. A ratio of one represents equal proportions; values above or below one indicate relative differences according to the direction of the comparison. The odds ratio compares odds rather than proportions. Its posted estimate is 1.584, with an interval from 1.007 to 2.489. Odds and proportions are different quantities, so an odds ratio should not be read as a risk difference or as a direct percentage-point change.

The ratio estimates and intervals give another view of the same binary endpoint, but they do not remove uncertainty or resolve the discrepancy in the reported analyses. The registry does not report whether these ratio measures were part of the sponsor's prespecified analysis or how they were derived. Their presence should not be taken to imply that the sponsor's reported test used each measure.

What does the reported test do?

The registry reports a Chi-squared analysis and p = 0.05 for the comparison. In general, a Chi-squared test assesses whether observed counts across categories differ from counts expected under a null hypothesis of no association, given the test's assumptions. In a two-group binary-outcome setting, it uses the counts meeting and not meeting the endpoint in each group. The registry does not report additional details about the test implementation, any continuity correction, or whether the test was adjusted for other variables.

The simple unadjusted recalculation from the posted counts gives p = 0.045. It is not the sponsor's reported result. Since the record marks a discrepancy, the sponsor's own analysis takes precedence. This difference also illustrates why a p-value cannot be interpreted independently of the method and analysis specification: alternative implementations or data handling can produce differing results. The registry does not provide enough detail to identify the reason for this difference.

Why distinguish adjusted and unadjusted analyses?

An unadjusted comparison uses the group summaries without accounting for other covariates. In general, an adjusted analysis can account for prespecified participant or design characteristics, but its interpretation depends on the adjustment model and variables. No adjustment variables or adjusted estimate are reported in the registry record. The posted recalculation is explicitly unadjusted, and should not be described as an adjusted treatment effect.

Random assignment is intended to support a fair comparison of groups, but it does not eliminate the need to describe how outcomes were analyzed, how missing values were handled, or which participants were included. The registry record does not report an intention-to-treat or per-protocol population, a missing-data procedure, or a participant-flow account for the primary outcome. The different group sizes in the primary-outcome and safety listings make it especially important not to assume that the same analysis population was used for every result.

Multiplicity is another general statistical consideration when several outcomes or analyses are examined. Testing multiple hypotheses can increase the chance of at least one apparently notable result if no adjustment or prespecified hierarchy is used. The registry lists four outcome measures and four analyses, but does not report whether multiplicity was addressed, how outcomes were ordered, or which analysis was designated primary in the full statistical plan. The primary endpoint is identified in the registry, but the broader analysis strategy is not reported.

10. Confidence Intervals and Precision

The primary-outcome risk-difference estimate is 0.068, with an interval from -0.001 to 0.137. This interval spans zero. In practical statistical terms, the posted estimate is not highly precise enough to exclude a small difference in the opposite direction under the interval's bounds, and it also includes larger positive differences. The point estimate should not be read as though it were known without uncertainty.

The registry also reports a risk ratio of 1.086, with an interval from 0.997 to 1.184, and an odds ratio of 1.584, with an interval from 1.007 to 2.489. For ratio measures, the null value is one rather than zero. The risk-ratio interval includes one, whereas the odds-ratio interval as listed does not. These intervals are based on different scales and can convey different impressions; neither should be substituted for the other. The confidence level is not reported in the registry record.

The sponsor's reported Chi-squared p-value is 0.05, while the simple unadjusted recalculation gives p = 0.045. The discrepancy means the recalculated value should not be treated as the sponsor's result. The sponsor's own analysis takes precedence. Neither p-value gives a direct measure of the precision or importance of the effect; the estimate and interval are needed to understand the range of values compatible with the analysis.

Precision is also limited by what the registry makes available. It does not report the full analysis plan, handling of missing outcome data, or the confidence level. The endpoint group sizes are not the same as the serious-adverse-event risk groups, and the reason is not reported. These gaps make it difficult to assess whether the displayed estimates account for all randomized participants or whether other analyses would materially change the uncertainty.

11. 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 planning figures are participants per arm, not total participants, and they are illustrations based on the observed effect rather than the trial's original design. The assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning row uses the stated fraction of the observed effect as the effect to detect. The trial's own original sample-size assumptions and justification are not reported in the registry record.

For planning for 100% of the observed effect, the figures are 508 participants per arm for 80% power and 680 participants per arm for 90% power. For planning for 75% of the observed effect, they are 937 participants per arm for 80% power and 1,253 participants per arm for 90% power. For planning for 50% of the observed effect, they are 2,179 participants per arm for 80% power and 2,916 participants per arm for 90% power.

In general, power is the chance that a study would meet a defined statistical criterion if a specified effect were the true effect, under the planning assumptions. The 80% column describes a planned design with 80% power for the effect used in that row; the 90% column describes a planned design with 90% power for that effect. The figures are not guarantees about a future result. The listed planning curve corresponds to these assumptions and effect choices. Smaller effects require more participants to achieve the same planned power. These figures are not observed power.

12. 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 = 0.784; treatment proportion p₁ = 0.852; average p̄ = 0.818.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5456 = 1.0693.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5435 = 0.4574.
4. n = (1.0693 + 0.4574)² / (0.0677)² = 507.9, rounded up to 508 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 <- 0.784210526315789                          # control proportion
p1 <- 0.85195530726257                          # 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(2777580)
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 = 508 (80% power), 680 (90% power)
 75% of observed effect: n per arm = 937 (80% power), 1,253 (90% power)
 50% of observed effect: n per arm = 2,179 (80% power), 2,916 (90% power)
power.prop.test: 507.9 
Simulated power at n = 508 per arm: 0.800 (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.

13. Analyses Reported by the Sponsor

The registry reports the sponsor's analysis as a Chi-squared test with p = 0.05. The simple unadjusted recalculation from the posted outcome counts gives p = 0.045 and a risk difference of 0.068, with an interval from -0.001 to 0.137. The record flags a discrepancy between the sponsor's analysis and the recalculation. The sponsor's own analysis takes precedence; the recalculated result is a descriptive check of the posted summary counts, not a replacement for the sponsor's reported analysis.

The registry does not explain why the p-values differ. It does not provide the sponsor's full test specification, the underlying analysis dataset, details of missing-data handling, or a reconciliation of analysis populations. Consequently, the difference cannot be attributed to a particular statistical choice or data issue. The reported p = 0.05 should be identified as the sponsor's result, while p = 0.045 should be identified only as the unadjusted recalculation.

Both values should be interpreted with the estimated effect and interval, and neither alone indicates clinical importance. The analysis details available in the registry do not establish whether the sponsor's test was adjusted or whether it followed a prespecified plan.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures and four analyses, but does not post secondary outcome results. It identifies successful reperfusion as the primary outcome. The registry record does not report a hierarchy among outcomes, a multiplicity adjustment, or a plan for controlling the overall chance of a false-positive finding across analyses. The available information therefore does not establish how multiplicity was addressed in the trial's statistical plan.

In general, multiplicity matters when several statistical hypotheses are tested. If many tests are considered without an appropriate plan, the chance of at least one result appearing notable by chance can increase. This general concern does not establish that the trial's results are invalid; it identifies a design and interpretation detail that is not documented in the registry record. With secondary results absent, the primary outcome cannot be assessed in the context of a complete outcome set.

The registry does not report how missing primary-outcome data were handled, whether all randomized participants were included in the primary analysis, or whether an intention-to-treat, modified intention-to-treat, or per-protocol population was used. It also does not report exclusions from analysis, reasons for missingness, or sensitivity analyses. These omissions prevent a reader from determining from the registry alone how the analysis population was constructed.

The primary-outcome counts use group sizes of 358.0 and 190.0. Serious-adverse-event risk groups are listed as 401 and 203. The reason for these differing denominators is not reported in the registry record, so they should not be used to infer how many participants were missing from any specific analysis. The enrollment figure is 609, but the record does not provide a participant-flow explanation reconciling enrollment with the outcome-specific group counts.

15. 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

Serious events with the highest arm-level rate: cardiogenic shock (5.4%), heart failure (4.4%), reinfarction (2.5%), myocardial rupture (1.7%), intracranial hemorrhage (1.5%).

The serious-adverse-event listing gives a risk group of 401 for the pharmaco-invasive strategy, with 69 affected, and a risk group of 203 for standard primary PCI, with 32 affected. The record also lists deaths as 37 and 18, respectively. These are registry counts; no comparative effect estimate or interval for these safety outcomes is reported. The serious-adverse-event denominators differ from the primary-outcome group sizes, and the reason is not reported in the registry record.

The registry lists cardiogenic shock (5.4%), heart failure (4.4%), reinfarction (2.5%), myocardial rupture (1.7%), intracranial hemorrhage (1.5%), and major nonintracranial bleeding (1.2%) among the top serious terms. The record does not state the denominator or group attribution for these percentages in the listing, so they should not be assigned to a particular arm or used to calculate a between-group comparison.

Both groups have zero affected for the separately listed other-adverse-event category, with risk groups of 401 and 203. The record does not provide further detail about the category definition, ascertainment, follow-up duration, or causal attribution. Serious adverse events and deaths are important descriptive safety information, but these counts alone do not establish whether events were caused by the assigned strategy or whether the groups differed reliably in risk.

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

The posted primary-outcome counts show that more participants met the endpoint in the pharmaco-invasive group in absolute count, but the groups have different outcome denominators. The comparison is more appropriately read through the reported effect estimate: a risk difference of 0.068, with an interval from -0.001 to 0.137. The interval includes zero, so the estimate remains compatible with no difference and with differences in either direction within its bounds. The risk ratio and odds ratio are additional descriptions of the same binary outcome, not separate clinical endpoints.

The sponsor's Chi-squared result is p = 0.05. A simple unadjusted recalculation gives p = 0.045, and the record identifies a discrepancy. The sponsor's own analysis takes precedence. The registry does not report a full statistical plan, adjustment details, or the confidence level for the listed intervals, so strong conclusions based on a single threshold or test would exceed what the record supports.

The endpoint is an early ECG measure defined by ST-segment resolution at 30 min after angiography or PCI. It does not establish a difference in outcomes that were not posted, such as longer-term events, and no secondary results are available in the registry record. The serious-adverse-event counts and deaths are descriptive listings; the registry does not provide comparative estimates or enough detail to determine causality from these counts.

The result therefore describes the posted comparison for one specified early reperfusion endpoint. It does not isolate the contribution of tenecteplase, antiplatelet therapy, antithrombin therapy, or the subsequent procedure, because the randomized contrast is between treatment strategies containing multiple components. Nor does the registry record, on its own, establish a broader conclusion about all eligible patients, other treatment settings, or outcomes not reported.

17. Why This Trial Matters Statistically

This trial illustrates how a clinical comparison can be defined around treatment strategies rather than single interventions. The pharmaco-invasive pathway combines drug treatment and later angiography or rescue intervention, while the comparator is primary PCI with treatment according to local standards. Statistically, that means the main estimate concerns the contrast between these overall pathways; it cannot identify the effect of an individual component within either pathway.

It also illustrates why counts, effect estimates, intervals, and test results should be read together. The raw endpoint counts differ, but group sizes also differ. The risk difference gives an absolute-scale comparison, while the risk ratio and odds ratio express relative comparisons on different scales. The risk-difference interval includes zero, and the sponsor's reported p-value differs from the unadjusted recalculation. A single headline number would conceal these distinctions.

The discrepancy between the sponsor's Chi-squared result and the recalculated result highlights the value of transparent analysis reporting. The registry record does not explain the discrepancy or provide the full statistical plan. In addition, the primary-outcome and safety denominators differ, and secondary outcomes are not posted. Those details influence how completely the results can be interpreted.

Finally, the posted endpoint is an early physiologic measure. It is useful to distinguish what that measure directly records from broader questions about safety and later clinical outcomes. Statistical interpretation is strongest when the endpoint, population, analysis method, uncertainty, and missing information are kept in view together.

18. 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 are specific to the information available for this trial. The registry describes an open-label comparison, so masking was not used. It does not report whether ECG assessment was blinded or independently adjudicated. The endpoint depends on ECG measurement at a specified time after angiography or PCI, and the registry does not describe the measurement or adjudication procedures.

The comparator includes a P2Y12 antagonist and antithrombin treatment according to local standards. The record does not specify which agents or protocols were used across settings. The intervention is also a package of therapies and procedures, so the posted comparison cannot separate the contribution of its individual components. The registry summary does not report further details on treatment adherence, crossover, or protocol deviations.

There is a difference between the primary-outcome group sizes, 358.0 and 190.0, and the serious-adverse-event risk groups, 401 and 203. The reason is not reported in the registry record. Although enrollment is listed as 609, no participant-flow account explains the analysis-specific denominators. The record also does not report missing-data handling or the primary analysis population.

The sponsor's reported p-value is 0.05, while the simple unadjusted recalculation gives p = 0.045; the reason for this discrepancy is not reported. The registry also does not report the confidence level for the listed intervals, original sample-size assumptions, multiplicity handling, or secondary outcome results. These gaps limit assessment of analysis choices and the completeness of the outcome picture.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: STrategic Reperfusion in Elderly Patients Early After Myocardial Infarction — NCT02777580.
• Registry record last updated 2024-10-04; status last verified 2024-07.
• Results first posted 2024-10-04.
• 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.

22. Record Summary

The registry describes a completed randomized, open-label, parallel-group phase 4 trial sponsored by KU Leuven. It compares a pharmaco-invasive strategy with standard primary PCI in patients aged ≥ 60yrs with acute ST-elevation myocardial infarction randomized within 3 hours of symptom onset. Enrollment is listed as 609.

The primary endpoint is successful reperfusion, defined as worst-lead ST-segment elevation resolution ≥ 50% at 30 min post angiogram/PCI. The posted risk difference is 0.068, with an interval from -0.001 to 0.137. The sponsor reports a Chi-squared p-value of 0.05; the unadjusted recalculation gives p = 0.045, with a discrepancy noted, so the sponsor's own analysis takes precedence.

The registry lists serious adverse events and deaths, but does not post secondary outcome results or explain the difference between primary-outcome and safety denominators. Further statistical-plan and analysis details are not reported in the registry record.