Tailored vs. Anatomical Ablation Strategy for Persistent Atrial Fibrillation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Tailored vs. Anatomical Ablation Strategy for Persistent Atrial Fibrillation (NCT04702451), a randomized na study. The primary outcome is Number of Participants Free From Documented AF After One Ablation Procedure.

2. Clinical Question

The registry states the hypothesis that adding dispersion-targeted ablation to pulmonary vein isolation would be superior to pulmonary vein isolation alone. The primary outcome therefore focuses on a specific clinical and procedural result: documented atrial fibrillation status after a single index procedure. It is not the same as freedom from atrial fibrillation or atrial tachycardia after one or two procedures, which is a secondary outcome. The outcome definition also allows anti-arrhythmic drug use, so it does not represent freedom from arrhythmia without medication.

3. Trial Design

This was a randomized, double-masked, parallel-group study listed as completed. The registry lists the phase as not applicable. Enrollment was 377 participants. The study began on 2021-02-12, and primary completion was recorded as 2023-12-27. Volta Medical is listed as the sponsor.

Participants were assigned to a tailored strategy or an anatomical strategy. The tailored arm is described as tailored ablation, and the anatomical arm as anatomical ablation. The study summary clarifies the distinction: the tailored approach targeted areas of spatio-temporal dispersion in addition to pulmonary vein isolation, while the anatomical approach targeted pulmonary vein isolation alone. The registry lists dispersion ablation plus pulmonary vein isolation, VX1 and pulmonary vein isolation among the interventions.

The primary outcome was assessed at 12 months and counted participants free from documented atrial fibrillation after one ablation procedure. Its population was a modified intention-to-treat group rather than every randomized participant: specified exclusions included participants deemed ineligible before ablation, participants who had no ablation, and participants lost to follow-up during the 3-month blanking period. The record does not describe the sequence generation or allocation concealment, how masking was implemented, or which roles were masked. The trial's original sample-size assumptions and detailed statistical analysis plan are 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.

Before assignment: Among the 377 patients enrolled, 3 patients did not receive any ablation, because their ablation was cancelled or postponed. They were therefore not randomized and exited the study.

Overall Study

Analysis population for the primary outcome, as defined in the registry: mITT: all randomized participants except for those who were deemed ineligible after randomization and before the ablation procedure, those who did not have any ablation procedure, and those lost to follow-up during the 3-month blanking 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.

Population: The baseline safety population included all randomized participants who underwent their first ablation procedure.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Free From Documented AF After One Ablation Procedure, measured over 12 months.

The primary endpoint counts participants who were free from documented atrial fibrillation at 12 months after a single index ablation procedure. The registry defines freedom as no documented atrial fibrillation episode longer than 30 seconds, whether or not anti-arrhythmic drugs were used. The result is a participant count in each group, with the analysis population defined by the registry's modified intention-to-treat criteria.

This endpoint addresses a specific question about arrhythmia status following one procedure. Counting participants makes the outcome directly interpretable as the number meeting the defined criterion in each group; the comparison can also be expressed as a difference in the proportions meeting it. General statistical context: a binary endpoint records whether each participant meets a defined condition, rather than measuring a continuous quantity such as time or symptom intensity.

The endpoint does not by itself capture freedom from atrial tachycardia, freedom after repeat procedures, or freedom from anti-arrhythmic drugs. Those distinctions matter because the registry lists broader AF/AT outcomes after one or two procedures as secondary outcomes. The primary endpoint is therefore a deliberately specific measure, not a complete account of every possible outcome after ablation.

7. Results Posted in the Registry

• Anatomical: 70.1% (124/177) versus 87.8% (158/180) on control; risk difference -17.7 percentage points (95% CI -26.0 to -9.4), risk ratio 0.80 (0.71–0.89); unadjusted two-proportion z-test p = <0.001.

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.

Number of Participants Free From Documented AF/AT After One or Two Ablation Procedures

• 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:
  • Anatomical: 71.2% (126/177) versus 75.6% (136/180) on control; risk difference -4.4 percentage points (95% CI -13.5 to 4.8), risk ratio 0.94 (0.83–1.07); unadjusted two-proportion z-test p = 0.350.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Anatomical and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants Free From Documented AF/AT After One Ablation Procedure

• 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:
  • Anatomical: 59.9% (106/177) versus 60.0% (108/180) on control; risk difference -0.1 percentage points (95% CI -10.3 to 10.1), risk ratio 1.00 (0.84–1.18); unadjusted two-proportion z-test p = 0.983.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Anatomical and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcome pattern is less decisive than the primary result. The two posted AF/AT comparisons have intervals that span no difference on the risk-difference scale, and their unadjusted p-values do not provide strong evidence against a no-difference model. This uncertainty should not be translated into a claim that the strategies are equivalent: the intervals allow for effects in more than one direction.

These endpoints differ from the primary outcome in what they count. One combines freedom from documented AF/AT after one or two ablation procedures, while another concerns AF/AT after one procedure. The primary outcome is specifically freedom from documented AF after one procedure. The broader endpoints can therefore provide complementary context, but they do not replace the primary comparison or test exactly the same outcome definition.

The registry lists a safety composite endpoint among the secondary outcomes, but a comparative analysis for that endpoint is not posted with the secondary outcome comparisons. The adverse-event counts are reported separately and should not be mistaken for a complete statistical comparison of the named composite endpoint.

Unadjusted secondary results carry less weight when several outcomes are examined because repeated testing can increase the chance of at least one apparently notable result arising by chance. General statistical context: multiplicity procedures can address this issue, but the registry does not report whether any correction or hierarchy was prespecified. The secondary p-values should therefore be treated as unadjusted evidence, alongside the endpoint definitions and intervals, rather than as definitive confirmation or refutation of the primary finding.

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

• Number of Participants Free From Documented AF/AT After One or Two Ablation Procedures
• Number of Participants Free From Documented AF/AT After One Ablation Procedure
• Number of Participants With Complications (Safety Composite Endpoint)

9. Statistical Interpretation

10. Statistical Methods Explained

The posted primary outcome is binary at the participant level: each person either met the definition of freedom from documented AF or did not. The registry reports the number meeting the definition and the number in the analysis population for each group. It also reports a risk difference, relative risk, odds ratio, interval estimates and an unadjusted p-value for the comparison. These express the same group contrast on different scales; they are not separate outcomes.

What does the risk difference express?

The risk difference compares the proportion meeting the endpoint in one group with the proportion in the other. In the posted comparison, the direction is anatomical relative to tailored. A negative risk difference means the observed proportion meeting the endpoint was lower in the anatomical group. The estimate is -0.177. This scale expresses an absolute contrast in proportions, rather than a ratio. General statistical context: an absolute difference can be read as a direct separation between group probabilities, while a ratio describes one probability relative to another.

Why are relative risk and odds ratio also reported?

The relative risk compares the proportions in the two groups as a ratio. The odds ratio compares the odds of meeting the endpoint, where odds are the probability of the event divided by the probability of not meeting it. Both are relative measures, but they answer different mathematical questions and need not have the same numerical value. For common outcomes, odds ratios can be less intuitive as a description of relative probabilities. These measures should be interpreted with their stated direction and intervals, not treated as interchangeable with the risk difference.

What does a p-value tell the reader?

General statistical context: a p-value describes how unusual data at least as incompatible with a specified null model would be if that model and the test assumptions held. It is not the probability that the groups are truly identical, nor is it a measure of clinical importance. The primary result has an unadjusted p-value of <0.001. The registry record does not specify the testing procedure, whether the test was one- or two-sided, or a multiplicity adjustment. The sample-size planning illustration does state a two-sided significance level of 0.05, but that illustration is not a full description of the trial's original analysis plan.

How should the interval be read?

General statistical context: an interval expresses uncertainty around an estimate under a specified statistical method. For the primary risk difference, the posted endpoints are -0.260 and -0.095. Both are below zero, so the reported interval excludes the no-difference value on this scale. The registry does not state the interval's confidence level or how it was calculated. The interval describes uncertainty in the estimated group contrast; it does not cover every source of uncertainty, such as possible limitations in outcome ascertainment or analysis choices.

What population does the comparison represent?

The primary analysis population is called modified intention-to-treat in the record. It includes randomized participants except those deemed ineligible after randomization and before the ablation procedure, those without any ablation procedure, and those lost to follow-up during the 3-month blanking period. This is narrower than the full randomized enrollment. The registry does not report how many participants were excluded under each criterion, how other missing outcome data were handled, or whether any imputation was used.

The primary outcome is a count, but the comparison is naturally understood through the corresponding proportions because the group denominators differ. General statistical context: counts alone can be misleading when group sizes differ, so a comparison of proportions uses both the number meeting the endpoint and the number assessed. No new calculations are needed to interpret the posted comparison: the registry provides the group proportions and effect estimates. The record does not provide enough detail to reconstruct the full analysis or verify its model assumptions.

11. Confidence Intervals and Precision

The primary risk-difference estimate is -0.177 for anatomical relative to tailored. Its reported interval extends from -0.260 to -0.095. Both endpoints are negative, so the interval excludes zero, the no-difference value on the risk-difference scale. The interval therefore supports a direction consistent with a lower observed proportion meeting the primary endpoint in the anatomical group, while also showing uncertainty about the size of that contrast.

The registry does not report the confidence level or the procedure used to construct the interval. It should therefore be described as the posted interval without assigning a confidence percentage. In general, an interval's width reflects statistical precision under its method: narrower intervals indicate less sampling uncertainty than wider ones, all else being equal. An interval does not account automatically for unreported design limitations, outcome measurement issues, or analytic choices.

For both secondary AF/AT comparisons, the posted intervals include zero on the risk-difference scale. That means the estimates are compatible with no difference as well as with effects in either direction under the interval method. This is a statement about uncertainty, not proof that the groups are equivalent. The registry does not report an equivalence margin or a non-inferiority margin, and no such conclusion should be inferred from intervals that include zero.

Precision also depends on the endpoint and analysis population. The primary result concerns freedom from documented AF after one procedure, while secondary endpoints include AF/AT and outcomes after one or two procedures. Their estimates and intervals address distinct questions. The study enrollment and endpoint counts alone do not establish the precision of every possible outcome comparison.

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

For the primary comparison, planning for 100% of the observed effect gives 82 participants per arm for 80% power and 110 participants per arm for 90% power. Planning for 75% of the observed effect gives 135 participants per arm for 80% power and 181 participants per arm for 90% power. Planning for 50% of the observed effect gives 277 participants per arm for 80% power and 370 participants per arm for 90% power. Smaller effects require more participants in these illustrations.

In general, power is the chance that a study will reject a specified null hypothesis under a particular assumed effect and analysis plan. The 80% and 90% columns describe different target chances of detecting the assumed effect if it is present, subject to the stated planning assumptions. They do not describe the chance that the trial result is correct. These figures are not observed power; they are prospective planning illustrations calculated from the observed effect, not evidence about the trial's original planning process.

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 = 0.878; treatment proportion p₁ = 0.701; average p̄ = 0.789.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5769 = 1.1306.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5631 = 0.4739.
4. n = (1.1306 + 0.4739)² / (-0.1772)² = 82.0, rounded up to 82 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 <- 0.877777777777778                          # control proportion
p1 <- 0.700564971751412                          # 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(4702451)
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 = 82 (80% power), 110 (90% power)
 75% of observed effect: n per arm = 135 (80% power), 181 (90% power)
 50% of observed effect: n per arm = 277 (80% power), 370 (90% power)
power.prop.test: 82 
Simulated power at n = 82 per arm: 0.815 (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. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and several secondary outcomes, but it does not report a prespecified multiplicity strategy. It is therefore not possible to determine from the registry record whether the primary endpoint was protected as the sole confirmatory test, whether secondary outcomes followed a testing hierarchy, or whether any adjustment was planned. The posted secondary p-values are unadjusted. When several outcomes are tested, the chance of at least one small p-value under a collection of no-effect hypotheses can increase; general statistical context, not a claim about what occurred in this trial.

The primary population is explicitly described as modified intention-to-treat and includes exclusions for participants deemed ineligible after randomization and before ablation, participants who did not undergo any ablation, and participants lost during the 3-month blanking period. This definition helps identify who contributed to the primary analysis, but it differs from a population containing every randomized participant. The registry does not provide counts for each exclusion category or explain why each participant was excluded.

Other missing-data details are not reported in the registry record. These include the number of missing primary endpoint assessments beyond the stated lost-to-follow-up exclusion, the handling of missing data at the 12-month assessment, any imputation method, and any sensitivity analyses for missing outcomes. The record also does not state whether participants were analyzed according to their assigned group in all circumstances or describe protocol deviations.

These omissions limit assessment of how robust the estimates are to analysis choices. They do not establish that a particular bias occurred; they mean the registry entry does not document enough information to evaluate it. The trial's original statistical analysis plan, detailed adjustment strategy, and procedures for controlling multiplicity are not reported in the registry record.

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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: fluid overload (4.8%), pericarditis or pericardial effusion (2.1%), vascular access complications (1.6%), cardiac tamponade or perforation (1.1%), bradycardia (0.5%).

The safety figures give counts for participants affected by serious and other adverse events in each group. Serious adverse events affected 21 of 187 participants in the tailored group and 11 of 183 in the anatomical group. Other adverse events affected 12 of 187 and 10 of 183, respectively. The registry also records 2 deaths in the tailored group and 0 in the anatomical group. These safety denominators differ from the primary endpoint analysis denominators.

The registry lists fluid overload at 4.8%, pericarditis or pericardial effusion at 2.1%, vascular access complications at 1.6%, cardiac tamponade or perforation at 1.1%, bradycardia at 0.5%, and severe cardiac decompensation at 0.5% among the top serious event terms. The denominator and event-counting rules for these percentages are not reported in the registry record.

These figures are descriptive counts, not a reported adjusted comparison of safety risk. The registry does not provide a statistical analysis for the safety composite endpoint in the posted outcome comparisons. Counts alone do not establish a causal relationship or explain differences between groups.

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

The posted primary data show a higher observed proportion meeting the defined freedom-from-AF endpoint in the tailored group than in the anatomical group. The reported risk difference and its interval indicate a contrast that is below zero when expressed as anatomical relative to tailored, and the unadjusted p-value is <0.001. These statements describe the registry's endpoint and analysis; they do not establish that every individual would have the same outcome under either strategy.

The result applies to documented AF after one procedure at 12 months, with or without anti-arrhythmic drugs, in the stated modified intention-to-treat population. It does not directly establish differences in freedom from AF/AT after repeat procedures, medication-free outcomes, long-term outcomes beyond the stated timeframe, or outcomes not reported in the registry. The secondary results do not provide equally clear evidence of a difference, and they are unadjusted.

General statistical context: statistical evidence, clinical relevance and applicability are related but distinct. A small p-value is not a measure of clinical importance, and an estimated group difference does not show what will happen to a particular participant. The registry record does not provide a threshold for a clinically important difference, so the posted estimates cannot be classified against such a threshold from this information alone.

The registry entry also does not document detailed methods for missing outcomes, multiplicity control, interval construction, or the original sample-size rationale. Those gaps constrain how fully the result can be assessed. The appropriate interpretation is bounded by the posted endpoint, populations, effect estimates and uncertainty; no conclusion about unreported outcomes or individual treatment decisions follows from these statistics.

17. Why This Trial Matters Statistically

This trial is statistically informative because it compares two distinct ablation strategies using a randomized parallel-group design and reports a defined primary endpoint with group counts and comparative estimates. Randomization is intended, in general, to support a fair comparison by balancing factors across groups on average, although the registry entry does not describe the allocation procedure in detail. The posted estimate can therefore be read as a randomized group comparison within the population and endpoint definition recorded.

The contrast between a patient-tailored strategy and a predefined anatomical strategy raises a methodological question beyond the specific treatment comparison: whether individualizing the target changes a measurable outcome. The primary endpoint is narrowly defined and the registry states the study's hypothesis, making the statistical question explicit. At the same time, the secondary endpoints show why a trial's conclusion depends on exactly what is measured: AF after one procedure is not identical to AF/AT after one or two procedures.

The record also illustrates the importance of effect estimates and intervals alongside p-values. The primary comparison has a reported effect estimate and an interval, while the secondary comparisons are more uncertain. Planning illustrations further show that required sample sizes depend strongly on the effect size being targeted. They should not be mistaken for the study's original design assumptions or for evidence of achieved power.

Finally, this record highlights the value of complete statistical reporting. Details about the analysis plan, multiplicity, missing data and interval methods would help readers evaluate the strength and scope of the findings. Distinguishing documented results from unreported methods is essential when interpreting clinical trial statistics.

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.

The registry entry does not report the original sample-size justification or the detailed statistical analysis plan. The sample-size figures available are illustrations based on observed effects, not a substitute for the trial's prospective design rationale. The record also does not state the confidence level or construction method for the posted intervals, or the test procedure used for the p-values.

Important details about allocation concealment and implementation of double masking are not reported in the registry record. The extent to which participants, clinicians, outcome assessors or analysts were masked is not specified. The entry does not describe how AF was monitored or how documented episodes were captured, beyond the endpoint's episode-duration definition.

The modified intention-to-treat definition excludes specified participants, but the registry does not give exclusion counts by reason or explain handling of other missing endpoint data. Multiplicity control and the analysis population for secondary outcomes are not described. No comparative analysis is posted for the safety composite endpoint, and the denominators and event-counting rules behind the listed serious-event percentages are not stated.

These are reporting limitations, not evidence that a particular procedure was used incorrectly or that bias necessarily occurred. They limit independent assessment of the trial's analytic choices, missing-data sensitivity, and the relationship between the posted estimates and a prespecified analysis plan. The findings should be interpreted only for the outcomes, timeframes and populations described in the registry record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Tailored vs. Anatomical Ablation Strategy for Persistent Atrial Fibrillation — NCT04702451.
• Registry record last updated 2025-09-12; status last verified 2025-09.
• Results first posted 2025-09-12.
• 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 record describes a completed randomized, double-masked, parallel-group study of tailored ablation and anatomical ablation for persistent atrial fibrillation. Enrollment was 377. The primary endpoint was freedom from documented AF after one procedure at 12 months in a modified intention-to-treat population.

The posted primary comparison favors the tailored group in the observed endpoint proportions, with an unadjusted p-value of <0.001 and an interval for the risk difference that excludes zero. Secondary AF/AT comparisons are less conclusive, and the registry does not report a multiplicity strategy or detailed analysis plan. Safety counts are descriptive, with no posted comparative analysis for the safety composite endpoint.