Computed from this object's own state — a structural condition is unmet. This is not a fixed disclaimer: the conditions below are each testable, and a build in which they are met renders READY.
In Dabigatran, apixaban and edoxaban in atrial fibrillation, what do the contributing trials show?
In this section: Registration and administrative information (PROSPERO field set) · What this object claims to contain
| Review title | Dabigatran, apixaban and edoxaban in atrial fibrillation |
|---|---|
| Review question (PICO) | In Dabigatran, apixaban and edoxaban in atrial fibrillation, what do the contributing trials show? |
| Population | Adults with non-valvular atrial fibrillation eligible for oral anticoagulation (CHADS2 >=1 or CHA2DS2-VASc >=2) |
| Intervention | Direct oral anticoagulant (dabigatran, rivaroxaban, apixaban, or edoxaban) at the phase-3 licensed dose |
| Comparator | Dose-adjusted warfarin (VKA) targeting INR 2.0-3.0 |
| Background / rationale | Not recorded — this object holds no background field, and an introduction generated without one would be argument that no source in this review supports |
| Eligibility criteria | not recorded on the page this object was extracted from |
| Information sources | 0 source layers, listed on the Extraction tab |
| Search strategy | The executed strings, datetimes, filters and hit counts are on the Search tab |
| Study selection process | Not recorded — no screening record was recoverable from the page this object was extracted from, so who screened and how cannot be stated |
| Number of screeners | Not recorded — this object records no screener count |
| Data extraction items | Extracted per trial on this object: registry id; primary publication; arms; per-arm counts and the published effect; the randomised total, separately from the analysed denominator. Fields not listed here were not extracted. |
| Outcomes and prioritisation | Multiple trial-declared outcomes: Yearly Event Rate for Composite Endpoint of Stroke/SEE | The Composite Event of Stroke/Non-CNS Systemic Embolism: Primary Efficacy (Non-Inferiority) | Number of Participants With First Event of Ischemic/Unspecified Stroke, Hemorrhagic Stroke, or Systemic Embolism (SE) Du | Compare Edoxaban to Warfarin for Composite of Stroke and Systemic Embolic Events (SEE). |
| Risk of bias method | Not recorded — no per-domain RoB-2 assessment exists yet |
| Synthesis methods | Not recorded — no outcome on this object carries a pooled estimate, so no synthesis method was applied |
| Subgroup analyses | Not recorded — this object records no subgroup-analysis field at all, so whether any were prespecified is UNKNOWN -- which is not the same as none having been |
| Meta-bias assessment | Not recorded — no funnel, Egger or Peters value is held on this object, so no meta-bias assessment is claimed |
| Certainty assessment | Not recorded — no GRADE record was recoverable from the page this object was extracted from |
| Funding | Not recorded — no funding statement is recorded for this review |
| Competing interests | Not recorded — no declaration is recorded |
| Built | 2026-08-17T12:06Z |
| Schema | 2-converted-from-extractor |
not recorded on the page this object was extracted from
In this section: Extracted values, and where each came from · References · Included studies · Regulatory documents · Methods and guidance · Sources · Multiple trial-declared outcomes: Yearly Event Rate for Composite Endpoint of Stroke/SEE | The Composite Event of Stroke/Non-CNS Systemic Embolism: Primary Efficacy (Non-Inferiority) | Number of Participants With First Event of Ischemic/Unspecified Stroke, Hemorrhagic Stroke, or Systemic Embolism (SE) Du | Compare Edoxaban to Warfarin for Composite of Stroke and Systemic Embolic Events (SEE) · Multiple trial-declared outcomes: Yearly Event Rate for Composite Endpoint of Stroke/SEE | The Composite Event of Stroke/Non-CNS Systemic Embolism: Primary Efficacy (Non-Inferiority) | Number of Participants With First Event of Ischemic/Unspecified Stroke, Hemorrhagic Stroke, or Systemic Embolism (SE) Du | Compare Edoxaban to Warfarin for Composite of Stroke and Systemic Embolic Events (SEE) · What was measured · Pooled result · Contributing trials · Endpoint definitions, read from the registry · Named on this review, contributing nothing to its pool
One row per extracted value. Every row carries the value, the verbatim sentence it was read from, a resolvable link to the source, and whether the number was read or derived. Where any of those is absent the row says so rather than omitting the value.
| Trial / outcome | Value as extracted | Verbatim source sentence | Source links | Read or derived |
|---|---|---|---|---|
| RE-LY primary | OR 0.66 (95% CI 0.529 to 0.824) | no source sentence recorded — this value cannot be checked against a quoted line here | NCT00262600 | DERIVED by us from extractor recovery from the published page The point estimate and interval shown here are DERIVED, not read: the extractor recovered an estimate and a variance on the analysis scale, and the interval is estimate +/- 1.96*sqrt(variance) back-transformed. No source document was consulted and no source sentence is recorded. |
| ARISTOTLE primary | OR 0.792 (95% CI 0.659 to 0.951) | no source sentence recorded — this value cannot be checked against a quoted line here | NCT00412984 | DERIVED by us from extractor recovery from the published page The point estimate and interval shown here are DERIVED, not read: the extractor recovered an estimate and a variance on the analysis scale, and the interval is estimate +/- 1.96*sqrt(variance) back-transformed. No source document was consulted and no source sentence is recorded. |
| ENGAGE AF-TIMI 48 primary | OR 0.873 (95% CI 0.744 to 1.02) | no source sentence recorded — this value cannot be checked against a quoted line here | NCT00781391 | DERIVED by us from extractor recovery from the published page The point estimate and interval shown here are DERIVED, not read: the extractor recovered an estimate and a variance on the analysis scale, and the interval is estimate +/- 1.96*sqrt(variance) back-transformed. No source document was consulted and no source sentence is recorded. |
| Layer | Source | How it was obtained |
|---|
| Comparator | not recorded on the page this object was extracted from |
|---|---|
| Estimand | not recorded on the page this object was extracted from — random-effects |
| Effect scale | reported on the log scale; nothing is pooled on this outcome |
What is confirmed, stated as prominently as what is wrong. (1) the four endpoint definitions agree in their components. All four registry records count the first occurrence of stroke or systemic embolism: RE-LY 'stroke or systemic embolic event', rocket af 'a stroke or non-CNS systemic embolism', ARISTOTLE 'Ischemic/Unspecified Stroke, Hemorrhagic Stroke, or Systemic Embolism', ENGAGE 'the composite of stroke and Systemic Embolic Events'. That is real agreement, read from four independent records, and it is not the reason this estimate is withdrawn. (2) aristotle's per-trial value on the page is exactly right. The page publishes 0.79 (0.66 to 0.95) and the registry's own Cox analysis is 0.79 (.66 .95), digit for digit. (3) aristotle's and engage's stored counts reconcile exactly to the registry -- 212 = 159 + 38 + 15 and 265 = 173 + 76 + 16 for ARISTOTLE; 296 of 7035 and 337 of 7036 are ENGAGE's registered superiority row. (4) every comparison points the right way. On all three pooled trials the arm carrying role treatment holds the doac's counts. The arm labels were wrong on all three and have been corrected here from the registry's arm sizes; not one role moved. What this withdrawal does not establish, written here so it is not read for more than it says: Not that these four trials cannot be pooled. Their components agree, and the published literature pools exactly these four for exactly this composite. What cannot stand is this pool: three count-derived odds ratios where four registered hazard ratios exist, a fourth trial dropped in silence, and a headline that is the comparator. The replacement question is identified and deliberately not taken. It is to pool the four registered hazard ratios rather than derive odds ratios from counts. It is not taken because reading the registry to establish the above meant reading those hazard ratios, so their answer is already known to whoever would choose the question -- the same rule that parked ABLATION_AF and SGLT2_CKD. It also has a real obstacle that has to be decided by a person and not guessed: ENGAGE registers five primary analyses of one composite whose hazard ratios run 0.79, 0.86 and 0.87, and rocket af's registered analyses are both 'while on treatment' while ARISTOTLE's is an intended-treatment period. Choosing among those is choosing the estimand. Parked.
Multiple trial-declared outcomes: Yearly Event Rate for Composite Endpoint of Stroke/SEE | The Composite Event of Stroke/Non-CNS Systemic Embolism: Primary Efficacy (Non-Inferiority) | Number of Participants With First Event of Ischemic/Unspecified Stroke, Hemorrhagic Stroke, or Systemic Embolism (SE) Du | Compare Edoxaban to Warfarin for Composite of Stroke and Systemic Embolic Events (SEE).. k = 3.
| Trial | Analysed treatment / control |
OR (95% CI), or events | Source of this cell |
|---|---|---|---|
| RE-LY NCT00262600 | intervention: 6,076 control: 6,022 | 0.6599 (0.5285 to 0.8239) | : |
| ARISTOTLE NCT00412984 | intervention: 9,120 control: 9,081 | 0.7917 (0.6593 to 0.9507) | : |
| ENGAGE AF-TIMI 48 NCT00781391 | intervention: 7,035 control: 7,036 | 0.8731 (0.7442 to 1.024) | : |
This outcome's name is a concatenation of the trial-declared outcome titles the converter found, produced automatically. It therefore names a trial the pool does not contain -- rocket af, whose title is the second segment -- while the pool holds k=3. The mismatch is left in place rather than tidied away, because it is the artefact that shows the missing trial was expected; see the card below headed 'Named on this review, contributing nothing to its pool'. The definition that matters is recorded per trial, from each trial's own registry record, under inputs.trials[].by_outcome.primary.outcome_definition, and is rendered on this page under 'Endpoint definitions, read from the registry'.
What each trial COUNTED, in its own registry record's words, before anything here was pooled. A sentence saying what HAPPENED is not a sentence saying what was COUNTED, and only the second one licenses a pool. Read from the registry on 2026-08-18. Follow the registration link to disagree with any row.
| Trial | Rank in its own trial | Registered outcome measure | Description, verbatim | Analysis set / window |
|---|---|---|---|---|
| RE-LY NCT00262600 | PRIMARY -- this trial's own primary outcome measure | Yearly Event Rate for Composite Endpoint of Stroke/SEE | Time to first occurrence of stroke or systemic embolic event. Yearly event rate (%) = number of subjects with event / subject-years \* 100. Subject years = sum(date of study termination - date of randomization + 1) of all randomized subjects / 365.25 | Randomised, 36 months. The registered primary is a rate, not a count: 'Yearly event rate (%) = number of subjects with event / subject-years * 100'. The registry record carries no event counts for this outcome at all -- only yearly rates (dabigatran 150 mg 1.11, warfarin 1.71) against participant denominators. The 134 and 199 this object holds are not in this registry record. |
| ARISTOTLE NCT00412984 | PRIMARY -- this trial's own primary outcome measure | Number of Participants With First Event of Ischemic/Unspecified Stroke, Hemorrhagic Stroke, or Systemic Embolism (SE) During the Intended Treatment Period | All suspected efficacy events were adjudicated by the Central Events Committee (CEC). Diagnosis of stroke=the nontraumatic focal neurological deficit lasting at least 24 hours, and includes ischemic stroke, hemorrhagic stroke, ischemic stroke with hemorrhagic conversion, stroke of uncertain type, and retinal ischemic event (embolism, infarction). Diagnosis of SE=clinical history consistent with an acute loss of blood flow to a peripheral artery (or arteries), supported by evidence of embolism from surgical specimens, autopsy, angiography, vascular imaging, or other objective testing. | Intended treatment period -- randomisation to a pre-set efficacy cut-off date (30-Jan-2011), fixed before unblinding. |
| ENGAGE AF-TIMI 48 NCT00781391 | PRIMARY -- this trial's own primary outcome measure | Compare Edoxaban to Warfarin for Superiority for Composite of Stroke and Systemic Embolic Events (SEE). | Compare edoxaban to warfarin for the composite of stroke and Systemic Embolic Events (SEE) during the overall study period in the ITT analysis set with a superiority analysis. | Overall study period, ITT analysis set, superiority analysis. The record carries five separate registered primary measures of the same composite -- on-treatment mITT, overall mITT, on-treatment per-protocol, overall per-protocol, and this one. They are not interchangeable: the registered hazard ratios for high-dose edoxaban against warfarin run 0.79, 0.86 and 0.87 across them. |
Rocket af (NCT00403767) is listed on this review's page and contributes nothing to its pool, and nothing on the page says so. The page's own AUTO_INCLUDE_TRIAL_IDS names four registrations and its embedded record for this one carries tE:null and cE:null -- no event counts. This review's per-trial values are odds ratios derived from 2x2 counts, so a trial with no counts silently drops out. k on the index card is 4. k in this object is 3. The missing trial is the one whose registered result is closest to no effect.
| Trial | Why it contributes nothing | What the registry holds |
|---|---|---|
| ROCKET AF NCT00403767 | no event counts on the page to derive an odds ratio ; the page carries only denominators (7081 and 7090) and a published hazard ratio | counts and a hazard ratio for both registered analyses: rivaroxaban 188 of 6958 against warfarin 241 of 7004, HR 0.79 (0.66 to 0.96), non-inferiority; and 189 of 7061 against 243 of 7082, HR 0.79 (0.65 to 0.95), superiority. The page publishes HR 0.88 (0.75 to 1.03) for this trial, which is neither, and its denominators 7081 and 7090 are neither registered analysis population. |
In this section: Multiple trial-declared outcomes: Yearly Event Rate for Composite Endpoint of Stroke/SEE | The Composite Event of Stroke/Non-CNS Systemic Embolism: Primary Efficacy (Non-Inferiority) | Number of Participants With First Event of Ischemic/Unspecified Stroke, Hemorrhagic Stroke, or Systemic Embolism (SE) Du | Compare Edoxaban to Warfarin for Composite of Stroke and Systemic Embolic Events (SEE) · Forest plot · Risk of bias · GOSH · Trial-sequential analysis · Meta-regression
Drawn from the same stored estimates the table above lists. Box area is proportional to inverse-variance weight.
x-axis range
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All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: 63cfd55b4af47c3d), at 600 dpi for a 6-inch print width, on a white ground. They are not screenshots of the page and do not change with the theme you are reading in.
Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — forest_fit.eps, 4 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — forest_fit.tiff, 12,129 KB.
⬇ SVG (vector) 2 KB ⬇ PNG 4500x920 118 KB
All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: 6cf51934d0d9b71b), at 600 dpi for a 6-inch print width, on a white ground. They are not screenshots of the page and do not change with the theme you are reading in.
Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — forest_w1.eps, 4 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — forest_w1.tiff, 12,129 KB.
⬇ SVG (vector) 2 KB ⬇ PNG 4500x920 118 KB
All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: 534383e49333cb5b), at 600 dpi for a 6-inch print width, on a white ground. They are not screenshots of the page and do not change with the theme you are reading in.
Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — forest_w2.eps, 4 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — forest_w2.tiff, 12,129 KB.
Changing the range moves the axis window only. The guides stay labelled with the null and the extremes of the plotted intervals, so no plotted value and no printed number differs between these views — and that is checked at build time, not asserted. Ranges not offered because they would crop the data: 0.7 to 1.3.
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Only the vector format is offered for this figure, by choice: it is line art — discrete marks, glyphs and labels — which SVG reproduces exactly at any size, so a raster would add weight without adding fidelity. The build was able to rasterise; it was asked not to.
Not drawn, because there is nothing to draw it from.
⬇ SVG (vector) 1 KB ⬇ PNG 3500x540 80 KB
All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: dd33d4f986f7c7c5), at 600 dpi for a 6-inch print width, on a white ground. They are not screenshots of the page and do not change with the theme you are reading in.
Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — gosh.eps, 2 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — gosh.tiff, 5,537 KB.
Deliberately not drawn. Every subset meta-analysis of 3 trials is 7 points; a cloud that small cannot show the multimodality GOSH exists to reveal, and a reader would take the picture as evidence of its absence.
⬇ SVG (vector) 1 KB ⬇ PNG 3500x650 87 KB
All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: 25ed9800fdf56614), at 600 dpi for a 6-inch print width, on a white ground. They are not screenshots of the page and do not change with the theme you are reading in.
Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — tsa.eps, 2 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — tsa.tiff, 6,665 KB.
TSA boundaries depend entirely on a target information size that must be pre-specified. This review's protocol registers none, so any boundary drawn here would be a parameter chosen after seeing the data -- which is the practice TSA exists to protect against.
⬇ SVG (vector) 1 KB ⬇ PNG 3500x540 87 KB
All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: 2316b730fa24744e), at 600 dpi for a 6-inch print width, on a white ground. They are not screenshots of the page and do not change with the theme you are reading in.
Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — bubble.eps, 2 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — bubble.tiff, 5,537 KB.
The protocol pre-specifies no moderator, and at k = 3 a meta-regression would be fitted on 3 points. Not drawn rather than drawn with a caveat: a bubble plot invites reading a slope, and there is no slope here that any reader should read.
In this section: Summary of findings · Reproducibility artifact · Other recorded qualifications
| Outcome | k | Pooled effect | Certainty |
|---|---|---|---|
| Multiple trial-declared outcomes: Yearly Event Rate for Composite Endpoint of Stroke/SEE | The Composite Event of Stroke/Non-CNS Systemic Embolism: Primary Efficacy (Non-Inferiority) | Number of Participants With First Event of Ischemic/Unspecified Stroke, Hemorrhagic Stroke, or Systemic Embolism (SE) Du | Compare Edoxaban to Warfarin for Composite of Stroke and Systemic Embolic Events (SEE). | 3 | not pooled | See comment12 |
| Canonical object | — |
|---|---|
| Registered at | — — |
| Schema | 2-converted-from-extractor |
| Object last updated | 2026-08-17T12:06Z |
| Source object SHA-256, first 16 hex characters | 1eaf82ac3c842406 |
| Page generated | 2026-08-28 07:27 UTC |
| Generator build | 59b484ca7. The standard this page was built to is NOT ESTABLISHED: this object carries no build_stamp, so the version above is the standard that exists now, not the one this page was built against. |
This page CANNOT be rebuilt from what is recorded here: no canonical object is recorded and no registered commit is recorded. Each figure on the Analysis tab downloads as an SVG carrying exactly the values shown.
Statements this review records about the limits of what it establishes, which are not shown elsewhere on this page. They are reproduced from the object verbatim and are not summarised.
| What the registry holds that the page does not | counts and a hazard ratio for both registered analyses: rivaroxaban 188 of 6958 against warfarin 241 of 7004, HR 0.79 (0.66 to 0.96), non-inferiority; and 189 of 7061 against 243 of 7082, HR 0.79 (0.65 to 0.95), superiority. The page publishes HR 0.88 (0.75 to 1.03) for this trial, which is neither, and its denominators 7081 and 7090 are neither registered analysis population. |
|---|---|
| Components as the registry states them | stroke (any type); systemic embolic event. First occurrence. |
| Analysis set as the registry states it | Randomised, 36 months. The registered primary is a rate, not a count: 'Yearly event rate (%) = number of subjects with event / subject-years * 100'. The registry record carries no event counts for this outcome at all -- only yearly rates (dabigatran 150 mg 1.11, warfarin 1.71) against participant denominators. The 134 and 199 this object holds are not in this registry record. |
| Components as the registry states them | ischaemic or unspecified stroke; haemorrhagic stroke; systemic embolism. The registry's stroke definition also admits ischaemic stroke with haemorrhagic conversion, stroke of uncertain type, and retinal ischaemic event. First occurrence. |
| Analysis set as the registry states it | Intended treatment period -- randomisation to a pre-set efficacy cut-off date (30-Jan-2011), fixed before unblinding. |
| Components as the registry states them | stroke (any type); systemic embolic event (SEE). First occurrence. |
| Analysis set as the registry states it | Overall study period, ITT analysis set, superiority analysis. The record carries five separate registered primary measures of the same composite -- on-treatment mITT, overall mITT, on-treatment per-protocol, overall per-protocol, and this one. They are not interchangeable: the registered hazard ratios for high-dose edoxaban against warfarin run 0.79, 0.86 and 0.87 across them. |
In this section: Paper · Title · Abstract · Introduction · Methods — search · Methods — eligibility criteria · Methods — outcomes sought at every registered rank · Results · Disagreements between sources · Limitations · Reporting guidelines · Note on registration · References · Figure legends · Figures · Trial characteristics · Notes on this record — sections not written, and why · Not reported in this record
Each statement below cites the record it came from; those sources are listed at the end of every section. Where the record holds nothing, the section says so by name rather than being left out, so a procedure that was not carried out can be told from one that simply was never mentioned.
Dabigatran, apixaban and edoxaban in atrial fibrillation1
titleQuestion. In Dabigatran, apixaban and edoxaban in atrial fibrillation, what do the contributing trials show?1
questionBackground. This review asks: In Dabigatran, apixaban and edoxaban in atrial fibrillation, what do the contributing trials show? It examines 3 randomised trials and does not pool them. The outcome sought is Multiple trial-declared outcomes: Yearly Event Rate for Composite Endpoint of Stroke/SEE | The Composite Event of Stroke/Non-CNS Systemic Embolism: Primary Efficacy (Non-Inferiority) | Number of Participants With First Event of Ischemic/Unspecified Stroke, Hemorrhagic Stroke, or Systemic Embolism (SE) Du | Compare Edoxaban to Warfarin for Composite of Stroke and Systemic Embolic Events (SEE).1
manuscript.introductionPrimary trials. No bibliographic search for primary trials was run. The 3 included trials were identified by reading named registrations on the dates recorded on each entry. The basis on which this object was verified is not recorded. What this object does not claim is not recorded. The bar this object had to clear is not recorded.1
bookkeeping_2026_08_21.the_search_its_date_and_its_databasesnot recorded on the page this object was extracted from1
screening.eligibilityEvery registered rank -- primary, secondary and other -- was read for 3 of 3 contributing trials before any decision about which outcomes could be combined; each records the time it was read.1
inputs.trials[].all_ranks_read_utcMultiple trial-declared outcomes: Yearly Event Rate for Composite Endpoint of Stroke/SEE | The Composite Event of Stroke/Non-CNS Systemic Embolism: Primary Efficacy (Non-Inferiority) | Number of Participants With First Event of Ischemic/Unspecified Stroke, Hemorrhagic Stroke, or Systemic Embolism (SE) Du | Compare Edoxaban to Warfarin for Composite of Stroke and Systemic Embolic Events (SEE).. These 3 trials are not pooled, and the reason is stated rather than the outcome being quietly omitted: The published estimate is the comparator, not the finding. The index card served 'Published: HR 0.81 (0.73 to 0.91), k=4'. This page's own bytes embed PUBLISHED_META_BENCHMARKS = Ruff 2014, 'Ruff pooled doac vs warfarin MA (stroke/SE)', measure RR, estimate .81, lci .73, uci .91, k 4, Lancet 2014;383:955-962 -- a locked local database of published syntheses this review is meant to be compared against. All four numbers on the card are those four numbers. This object's own pooled value is OR 0.7817 (0.6710 to 0.9108) at k=3 and shares no digit with the card. The one place the page held a correct external value is the value that migrated into the claim position, and the measure was relabelled from RR to HR on the way. Separately and sufficient on its own: k is overstated. The card and the page's AUTO_INCLUDE_TRIAL_IDS both say four trials; three are pooled. Rocket af carries no event counts on the page, so a pool derived from 2x2 counts drops it in silence, and it is the trial whose registered result is closest to no effect. Separately again: the measure is misnamed. Every per-trial value here is an odds ratio this project derived from 2x2 counts -- the object says so in its own its recorded note on how the value was derived -- while all four registry records register a Cox proportional-hazards analysis of time to first event and report a hazard ratio. A derived odds ratio was published under the label HR.1
outcomes[id=primary].name, results.by_outcome.primary.pooled.withdrawn_reasonnot recorded on the page this object was extracted from1
not recorded on the page this object was extracted from2
reconciliation.why_this_step_existsreconciliation.clean_becauseEligible trials that do not contribute: Rocket af (NCT00403767) is listed on this review's page and contributes nothing to its pool, and nothing on the page says so. The page's own AUTO_INCLUDE_TRIAL_IDS names four registrations and its embedded record for this one carries tE:null and cE:null -- no event counts. This review's per-trial values are odds ratios derived from 2x2 counts, so a trial with no counts silently drops out. k on the index card is 4. k in this object is 3. The missing trial is the one whose registered result is closest to no effect.1
1 claim(s) previously made about this review were corrected and the corrections are retained on the object rather than overwritten.2
What this review does not give a clinician: the number of events in each arm, any absolute effect or number needed to treat and any measure of harm. A relative effect cannot be turned into the benefit or the risk facing one patient without them, so this review can support a judgement about what these trials found and not a judgement about what to do.3
eligible_but_not_contributing.noteclaims_correctedresults.by_outcomeThis review reports against PRISMA 2020. A screening record is held on this object and the flow it supports is shown in the Methods. The completed PRISMA checklist and FLOW diagram are not held here: the venue requires them deposited in an approved repository with a DOI cited in the Data Availability Statement, and minting that DOI is an author action rather than a build step.1
screeningNo PROSPERO registration or protocol record is held on this object. That is not the same as knowing this review was not registered, and neither claim is made. It is recorded here as an absence so that a reader does not have to infer it from silence.1
bookkeeping_2026_08_21.whether_this_review_was_prospectively_registered| Trial | Registration | Registry | Read |
|---|---|---|---|
| NCT00262600 | ClinicalTrials.gov | ||
| NCT00412984 | ClinicalTrials.gov | ||
| NCT00781391 | ClinicalTrials.gov |
| Cited for | Reference |
|---|---|
| the reporting guideline this manuscript is written against | Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi:10.1136/bmj.n71 |
manuscript.referencesmanuscript.references| Outcome | Figure | What it shows |
|---|---|---|
| Multiple trial-declared outcomes: Yearly Event Rate for Composite Endpoint of Stroke/SEE | The Composite Event of Stroke/Non-CNS Systemic Embolism: Primary Efficacy (Non-Inferiority) | Number of Participants With First Event of Ischemic/Unspecified Stroke, Hemorrhagic Stroke, or Systemic Embolism (SE) Du | Compare Edoxaban to Warfarin for Composite of Stroke and Systemic Embolic Events (SEE). | Forest plot | not pooled; the reason is given in Results |
results.by_outcomeresults.by_outcome.primary.per_trial, results.by_outcome.primary.pooledresults.by_outcome.primary.per_trial, results.by_outcome.primary.pooled| Registration | Trial | Participants | Randomised | Primary outcome measured over | Design |
|---|---|---|---|---|---|
| NCT00262600 | RE-LY | not recorded on the page this object was extracted from | 18113 | 36 months | Dabigatran 150 mg (treatment, n=6076) vs Warfarin (control, n=6022) [+4 further fields recorded on the object] Dabigatran 150 mg (the recorded reason the label was corrected): registry arm size 6076 is the dabigatran 150 mg group Dabigatran 150 mg (the recorded note on the label correction): The label was wrong and the role was right, decided from the registry's own arm sizes. The converter took the protocol arm list in positional order -- first and last -- and attached those labels to counts that came from elsewhere. RE-LY's registry arms are Dabigatran dose 2, Warfarin and Dabigatran dose 1 and it skipped the middle one, which is the warfarin arm the numbers actually belong . Engage's are Warfarin/placebo edoxaban, high dose edoxaban/placebo warfarin and low dose edoxaban/placebo warfarin and it skipped the middle one again. Aristotle has two arms labelled '1' and '2' and it took them in order, putting the ACTIVE_COMPARATOR label on the apixaban counts. The direction of every comparison is correct: on all three trials the arm carrying role treatment holds the doac's counts. That is exactly why this survived -- the arithmetic is unaffected and every label a reader sees is on the wrong arm. Warfarin (the recorded reason the label was corrected): registry arm size 6022 is warfarin. The arm this object labelled 'Dabigatran dose 1' -- the 110 mg group -- has 6015. The two differ by 7 participants and that is what settles it. Warfarin (the recorded note on the label correction): The label was wrong and the role was right, decided from the registry's own arm sizes. The converter took the protocol arm list in positional order -- first and last -- and attached those labels to counts that came from elsewhere. RE-LY's registry arms are Dabigatran dose 2, Warfarin and Dabigatran dose 1 and it skipped the middle one, which is the warfarin arm the numbers actually belong . Engage's are Warfarin/placebo edoxaban, high dose edoxaban/placebo warfarin and low dose edoxaban/placebo warfarin and it skipped the middle one again. Aristotle has two arms labelled '1' and '2' and it took them in order, putting the ACTIVE_COMPARATOR label on the apixaban counts. The direction of every comparison is correct: on all three trials the arm carrying role treatment holds the doac's counts. That is exactly why this survived -- the arithmetic is unaffected and every label a reader sees is on the wrong arm. |
| NCT00412984 | ARISTOTLE | not recorded on the page this object was extracted from | 20976 | Time to first event in "Intended Treatment Period": started on day of randomization, ended at efficacy cut-off date (date target number of primary efficacy events [448] was expected to have occurred; set to 30-Jan-2011, prior to unblinding).; "Intended Treatment Period" started on the day of randomization and ended at the efficacy cut-off date (date on which it was expected that the target number of primary efficacy events [448] would have occurred; set to 30-Jan-2011, prior to unblinding). | Apixaban (treatment, n=9120) vs Warfarin (control, n=9081) [+4 further fields recorded on the object] Apixaban (the recorded reason the label was corrected): registry arm size 9120 is apixaban, and its registered primary counts 159 + 38 + 15 = 212, exactly the events this object holds Apixaban (the recorded note on the label correction): The label was wrong and the role was right, decided from the registry's own arm sizes. The converter took the protocol arm list in positional order -- first and last -- and attached those labels to counts that came from elsewhere. RE-LY's registry arms are Dabigatran dose 2, Warfarin and Dabigatran dose 1 and it skipped the middle one, which is the warfarin arm the numbers actually belong . Engage's are Warfarin/placebo edoxaban, high dose edoxaban/placebo warfarin and low dose edoxaban/placebo warfarin and it skipped the middle one again. Aristotle has two arms labelled '1' and '2' and it took them in order, putting the ACTIVE_COMPARATOR label on the apixaban counts. The direction of every comparison is correct: on all three trials the arm carrying role treatment holds the doac's counts. That is exactly why this survived -- the arithmetic is unaffected and every label a reader sees is on the wrong arm. Warfarin (the recorded reason the label was corrected): registry arm size 9081 is warfarin, and its registered primary counts 173 + 76 + 16 = 265, exactly the events this object holds Warfarin (the recorded note on the label correction): The label was wrong and the role was right, decided from the registry's own arm sizes. The converter took the protocol arm list in positional order -- first and last -- and attached those labels to counts that came from elsewhere. RE-LY's registry arms are Dabigatran dose 2, Warfarin and Dabigatran dose 1 and it skipped the middle one, which is the warfarin arm the numbers actually belong . Engage's are Warfarin/placebo edoxaban, high dose edoxaban/placebo warfarin and low dose edoxaban/placebo warfarin and it skipped the middle one again. Aristotle has two arms labelled '1' and '2' and it took them in order, putting the ACTIVE_COMPARATOR label on the apixaban counts. The direction of every comparison is correct: on all three trials the arm carrying role treatment holds the doac's counts. That is exactly why this survived -- the arithmetic is unaffected and every label a reader sees is on the wrong arm. |
| NCT00781391 | ENGAGE AF-TIMI 48 | not recorded on the page this object was extracted from | 21105 | on-treatment period 2.5 years of median study drug exposure and 2.8 year of median follow-up; overall study period 2.5 years of median study drug exposure and 2.8 year of median follow-up | High Dose Edoxaban/Placebo Warfarin (treatment, n=7035) vs Warfarin/Placebo Edoxaban (control, n=7036) [+4 further fields recorded on the object] High Dose Edoxaban/Placebo Warfarin (the recorded reason the label was corrected): registry: 296 of 7035 is the HIGH dose edoxaban group in the superiority analysis. This object carried the warfarin arm's label on it. High Dose Edoxaban/Placebo Warfarin (the recorded note on the label correction): The label was wrong and the role was right, decided from the registry's own arm sizes. The converter took the protocol arm list in positional order -- first and last -- and attached those labels to counts that came from elsewhere. RE-LY's registry arms are Dabigatran dose 2, Warfarin and Dabigatran dose 1 and it skipped the middle one, which is the warfarin arm the numbers actually belong . Engage's are Warfarin/placebo edoxaban, high dose edoxaban/placebo warfarin and low dose edoxaban/placebo warfarin and it skipped the middle one again. Aristotle has two arms labelled '1' and '2' and it took them in order, putting the ACTIVE_COMPARATOR label on the apixaban counts. The direction of every comparison is correct: on all three trials the arm carrying role treatment holds the doac's counts. That is exactly why this survived -- the arithmetic is unaffected and every label a reader sees is on the wrong arm. Warfarin/Placebo Edoxaban (the recorded reason the label was corrected): registry: 337 of 7036 is the warfarin group. This object carried the LOW dose edoxaban arm's label on it -- that arm has 383 of 7034. Warfarin/Placebo Edoxaban (the recorded note on the label correction): The label was wrong and the role was right, decided from the registry's own arm sizes. The converter took the protocol arm list in positional order -- first and last -- and attached those labels to counts that came from elsewhere. RE-LY's registry arms are Dabigatran dose 2, Warfarin and Dabigatran dose 1 and it skipped the middle one, which is the warfarin arm the numbers actually belong . Engage's are Warfarin/placebo edoxaban, high dose edoxaban/placebo warfarin and low dose edoxaban/placebo warfarin and it skipped the middle one again. Aristotle has two arms labelled '1' and '2' and it took them in order, putting the ACTIVE_COMPARATOR label on the apixaban counts. The direction of every comparison is correct: on all three trials the arm carrying role treatment holds the doac's counts. That is exactly why this survived -- the arithmetic is unaffected and every label a reader sees is on the wrong arm. |
inputs.trialsOf the four properties this project requires of a completed topic, 0 are held (none) and 4 are refused with the obstacle named in the evidence (the number of published syntheses this review was a GRADE certainty rating for each pooled outcome, the statistical model's output, quoted as it was produced, a risk-of-bias judgement for each reported result).1
bookkeeping_2026_08_21.which_limbs_this_review_refusesThe items below were not written because the record does not hold what they would be composed from. They are named here so that an absence is not mistaken for an omission.
| Article area | Item not reported | Reason |
|---|---|---|
| Abstract | The Background sentence of the abstract | Background is argument -- why this question matters -- and no arrangement of the quantities this object holds yields it. It is emitted only from an authored field and there is no composition path for it here |
| Abstract | The Methods sentence of the abstract | None of the method facts this would be composed from -- databases searched, eligibility, pooling model, risk-of-bias tool, certainty approach -- is recorded on this object |
| Abstract | The Results sentence of the abstract -- no outcome on this object carries a pooled point estimate, so there is nothing to report and none is manufactured here | The reason each pool is declined is given in Results |
| Abstract | The Conclusions sentence of the abstract | A conclusion is argument -- what a reader should now believe -- and it is emitted only from an authored field. Composing one from the estimate would be this renderer telling the reader what to conclude, which no field supports |
| Keywords | The keyword list | A content gap; no keywords are recorded and inventing them would be indexing this review under terms nobody chose |
| Methods — search | A database search for primary trials, which was not carried out for this review; the included trials were identified from named registrations | No further reason is recorded. |
| Methods — how many studies at each stage | The k cascade | No further reason is recorded. |
| Methods — synthesis | The model/estimator sentence for multiple trial-declared outcomes: Yearly Event Rate for Composite Endpoint of Stroke/SEE | The Composite Event of Stroke/Non-CNS Systemic Embolism: Primary Efficacy (Non-Inferiority) | Number of Participants With First Event of Ischemic/Unspecified Stroke, Hemorrhagic Stroke, or Systemic Embolism (SE) Du | Compare Edoxaban to Warfarin for Composite of Stroke and Systemic Embolic Events (SEE) | -- no pooled estimate was produced for this outcome, so no model was fitted and none is described |
| Methods — synthesis | The claim that records were screened in duplicate by two independent reviewers | No further reason is recorded. |
| Methods — synthesis | The claim that risk of bias was assessed with a named tool | No further reason is recorded. |
| Methods — synthesis | The claim that certainty of evidence was graded | No further reason is recorded. |
| Methods — synthesis | The claim that the review methods were prespecified before data collection | No further reason is recorded. |
| Risk of bias in the included results | The risk-of-bias assessment | No further reason is recorded. |
| Risk of bias in the included results | The risk-of-bias distribution | No further reason is recorded. |
| Certainty of the evidence | Certainty of the evidence, by outcome, with every rating step | No further reason is recorded. |
| Certainty of the evidence | The certainty assessment | No GRADE record is held, so the certainty column elsewhere on this page is an em dash rather than a guess |
| Discussion | The Discussion -- this is a content gap | The object records no interpretive text, and none is generated here: text written by the renderer would be an argument no field supports |
| Comparison with published syntheses | The comparison with published syntheses | No published synthesis is recorded for this topic, so no denominator can be given |
| Conclusions | The Conclusions -- this is a content gap | The object records no interpretive text, and none is generated here: text written by the renderer would be an argument no field supports |
| Data availability | The data availability statement | No further reason is recorded. |
| Software availability | The software and environment statement | No further reason is recorded. |
| Author contributions | The author-contributions statement | Who did what is a fact about people, and this object records none |
| Competing interests | The competing-interests declaration | F1000Research requires this section on every article, and requires explicit text where there is nothing to declare. It is a statement about the author and not about the evidence: no field of this object implies it and none is invented here |
| Grant information | The grant information | The venue requires each funder's name, the grant number where applicable, and the person the grant was assigned . None of that is derivable from a synthesis |
| Funding and conflicts of interest | The funding and conflict-of-interest statement -- a content gap | A submission requires it and this object does not carry it; it is not inferable from anything held here |
| Note on registration | The registration note | No further reason is recorded. |
| Registration | A registration statement: no prospective registration is recorded for this review, and whether one exists elsewhere has not been established | No further reason is recorded. |
| Extended data: statistical output, quoted verbatim | The verbatim model output | No analysis output is stored on this object, so nothing can be quoted and nothing is paraphrased in its place |
| Submission conformance | The submission conformance statement | No further reason is recorded. |
| Notes on this record — sections not written, and why | The list of refused properties | No further reason is recorded. |
UNSTAMPED — unknown-version. This page carries no build_stamp, so the standard it was built to cannot be established. That is a statement about the record, not a claim that the page is below standard.
Every number on this page is projected from a single canonical object, and each measured cell names the source analysis it was read from. That is what is machine-checked. It does not establish that the underlying sources are right, only that this page faithfully reports them.