Colchicine vs placebo for prevention of postoperative atrial fibrillation

Overview

Colchicine vs placebo for prevention of postoperative atrial fibrillation

In adults undergoing cardiac surgery, does peri-operative colchicine reduce postoperative atrial fibrillation versus placebo/usual care?

Primary outcome

Transparency (independently checkable)

30 of 30 numerical claims on this page (100%) carry a one-click source a reader can open to check independently — each pooled number its PMID/NCT and verbatim span, each declared-absent trial its reason, each risk-of-bias domain the structured field it read, the reproduction its protocol SHA and replay result. The published comparator exposes 2 such claim(s) — its reported estimate(s) with one citation; its per-trial inputs are not machine-exposed. Score: scripts/transparency_score.py (committed docs/transparency.json).

Stated limitations

• Small k on many topics. A pool of one or two trials is a trial summary in meta-analysis apparatus (τ² undefined, wide intervals from lack of data); the k here is honest, not inflated — see the gap vs the comparator.
• Open-access comparator only. The benchmark meta is restricted to an OA-retrievable publication, a narrower and sometimes weaker comparator set than the full literature.
• Favourable topic sample. Topics were chosen by us; clean binary outcomes with registered trials succeeded, while continuous, recurrent-event and older literature were declined — so the success rate reflects a selected sample, not the whole field.
• Risk of bias is partial. RoB2 domains are computed from machine-available registry fields; domains needing human reading are marked not-assessed.
• Registry snapshot is dated. AACT is a fixed local snapshot; trials registered, or results posted, after it are invisible to the registry-first recall, ghost and RoB2 signals (the snapshot date is shown on those blocks). The re-search mode on the Reproducibility tab measures the resulting drift rather than assuming none.
• Dual screening is not fully independent. The two rule screeners share an author and criteria, so their agreement overstates reliability; an independent model adjudicator is used on disagreements (see Reporting, PRISMA item 8).
• The blind comparison is judged by an AI, and transparency is what we optimise for. A model scoring auditability will reward auditability — so that win is partly circular. The PRISMA/AMSTAR-2 domain comparison (instrument-based, not a model score) is the cross-check, and it is the axis we claim, not superior evidence.

Protocol

# Protocol — colchicine for prevention of postoperative atrial fibrillation

**Registration.** The commit adding/updating this file registers the review; its SHA is
embedded in the page. Committed before the synthesis runs. Same machinery as topic 1.

## PICO
- **P** — adults undergoing cardiac (cardiothoracic) surgery.
- **I** — colchicine (peri-operative), added to usual care.
- **C** — placebo / usual care.
- **O (primary)** — postoperative atrial fibrillation (POAF).
- **O (harms)** — gastrointestinal adverse effects; treatment discontinuation.

## Estimand / population / timepoint
- RR of POAF, intention-to-treat, in-hospital / index-admission follow-up.

## Eligibility — P/I/C/DESIGN only
- **I1** RCT; **I2** cardiac-surgery population with POAF as an outcome; **I3** colchicine vs
  placebo/usual care; **design** double-blind OR placebo-controlled RCT.
- Exclude: **X1** not RCT; **X2** wrong population (ablation/pulmonary-vein-isolation AF,
  pericarditis, coronary-disease AF); **X3** no colchicine-vs-control contrast; **X5** off-topic
  (a primary trial of another topic in this set — negative control).
- Eligibility is NOT on the outcome axis; a published effect+CI is a poolable input.

## Synthesis method (DECLARED = served)
Random-effects inverse-variance on log(RR); Paule-Mandel τ²; HKSJ 95% CI on t_{k-1}
(floor max(1,Q/(k-1))); PI μ ± t_{k-1}·√(τ²+se²). DerSimonian-Laird forbidden. metafor-validated.
(Note: the comparator used DerSimonian-Laird; we report theirs as published and pool ours under the declared method.)

## Comparator (resolved; OA confirmed)
Zhao et al., *J Cardiothorac Surg* 2022, "A meta-analysis of colchicine in prevention of atrial
fibrillation following cardiothoracic surgery or cardiac intervention" (PMID 36050741,
PMC9438305, DOI 10.1186/s13019-022-01958-9; open access). Reports POAF RR 0.62 (0.52–0.74) over 9 RCTs.

## Controls
- **Positive** — the search recovers the colchicine-vs-placebo cardiac-surgery POAF RCTs the comparator pools.
- **Negative** — CORP (colchicine for recurrent pericarditis, PMID 21873705 — another topic in this set)
  must be recovered and EXCLUDED (wrong population).

Search

Source status (which adapters ran)

Citation chase: NOT_RUN · ClinicalTrials.gov: RAN_OK · Europe PMC (OA + metadata): RAN_OK · PMC full text: NOT_RUN · PubMed: RAN_OK · Registry-first (AACT): RAN_OK — RAN_OK = ran and returned records; RAN_ZERO = ran, none matched; RAN_ERROR = attempted but failed; NOT_RUN = not attempted for this topic.

Registry-first recall (reach)

Registry-first RECALL: recovered 3/5 of this topic's known trials (enumerated 23; status RAN_OK). Reachable ceiling 4/5: 1 trial(s) are registered but not enumerated by the committed query (registry vocabulary limit — improvable). 1 missed trial(s) have no own-publication registry linkage — unregistered / pre-registration-era, so unreachable by any registry-first search (a property of the literature, not a search failure). Missed: 27502857, 29237033. Measured 2026-09-11T23:39:14Z. Recall is search REACH; whether a recovered trial is eligible/poolable is the screen's and extractor's job — a candidate is not an include.

Registry landscape & unpublished evidence (AACT)

Of 23 registry records matching the query (broad — reach, not precision): 10 have a linked publication; 3 have posted CT.gov results but no publication (poolable unpublished data no published meta in this topic has); 1 are completed ≥12 months ago with neither results nor a linked publication — a loose upper bound on non-publication, inflated by the broad enumeration and by NCT→PMID linkage misses, not a publication-bias claim. AACT 2026-08-30 (local snapshot).

PubMed

colchicine AND atrial fibrillation AND (postoperative OR cardiac surgery OR postpericardiotomy) AND (randomized OR randomised OR trial)

colchicine prevention postoperative atrial fibrillation placebo randomized

ClinicalTrials.gov

{"cond": "postoperative atrial fibrillation", "intr": "colchicine"}

Screening

Study selection flow (PRISMA 2020)

Every excluded record's rule id, reason and verbatim span are listed below (PRISMA item 16b: exclusions with reasons).

Dual independent screening (PRISMA item 8)

Two independently-implemented rule screeners over 67 records: agreement 61/67, disagreement 9.0% (6 records). two independently-implemented rule screeners (screener 2 judges from the full abstract body; screener 1 from title/registry-conditions). Adjudicator: screener 1. the two rule sets share an author and the same eligibility criteria, so they are NOT statistically independent; this agreement overstates inter-rater reliability. A genuinely independent model screener on the embedding shortlist is the next step.

Independent model adjudication of the disagreements

A capable model (different information + method than the two correlated rule sets) adjudicated 6 content-bearing disagreements; it agrees with the served rule screener on 5/6. an independent capable-model reader adjudicated the rule-screener disagreements (different information + method than the two correlated rule sets). Advisory: the rule screener remains the served decision; flags are surfaced for review. Flags: 39266309 (served exclude, model include: Colchicine RCT in the cardiac-surgery perioperative period; eligible at screening though its focus is organ damage.)

Trial integrity: none of the 5 trials pooled across all outcomes on this page is retracted (checked 2026-09-11T23:50:01Z via PubMed efetch (PublicationType + CommentsCorrections) + AACT dates).

67 records screened; 8 included. Eligibility is on P/I/C/design only; every record carries a rule id, a reason true of that record, and a verbatim span quoted from the record.

Controls

• Positive: Recovered & included the canonical trials ['25172965', '32720823', '29237033'] that a comparator includes; none missed.
• Negative: Cross-topic trial(s) ['21873705'] recovered by the search and correctly EXCLUDED ['21873705'] by rule (same drug/design, wrong topic).

Results

Postoperative atrial fibrillation (primary)

k = 5: the 5 trial(s) named below were pooled; 3 further screened-in trial(s) reported no poolable value for this outcome and are shown as declared absent.

Harms

Gastrointestinal adverse effects

k = 2: the 2 trial(s) named below were pooled; 6 further screened-in trial(s) reported no poolable value for this outcome and are shown as declared absent.

Treatment discontinuation

Comparator

Postoperative atrial fibrillation: 0.62 (RR), 95% CI 0.52–0.74

Gastrointestinal adverse effects: 2.65 (RR), 95% CI 1.83–3.84

Scope match (is this the same question?)

✓ same question. Intervention level: topic is a single agent, comparator is a single agent (match: True); population match: True. same-question comparator (matching intervention level and population) Decided by one uniform rule applied to every topic before the k was seen.

Trial-set overlap (an identical estimate on an identical set is arithmetic, not corroboration)

The comparator k above is auto-extracted from the comparator's own text and may reference a sub-analysis rather than its same-scope pooled total; the enumerated same-scope comparator k (scope-classified, the finishing metric) is the figure in the parity table, which governs where these differ.

Risk of bias

Coverage: 3 of 5 primary-outcome pooled trials have a registry (AACT) match and are assessed below; the other 2 are pooled but have no registry match (27502857, 29237033) and are shown as not assessed with the reason — never guessed.

Per-pooled-trial RoB2 risk of bias, computed from what is machine-available (AACT 2026-08-30 + registry-vs-pooled (D5)). Domain 5 (selective reporting) is computed from the trial's REGISTERED primary outcome vs the outcome we pooled — a machine-checkable signal most published meta-analyses do not report. D1/D2/D4 use AACT structured allocation/masking fields. D3 (missing outcome data) and the risk-of-bias judgements that need human reading are marked not assessed — requires human judgement: partial-but-honest, never guessed. Hover a cell for its basis.

Risk-of-bias sensitivity (re-pooled with the same estimator)

GRADE certainty (partial, object-derived)

Manuscript

Abstract

Question. In adults undergoing cardiac surgery, does peri-operative colchicine reduce postoperative atrial fibrillation versus placebo/usual care?

Methods. A prospectively registered, fully reproducible review: the protocol was committed before synthesis (registration SHA 17664842dc53); a registry-first search was screened by two independent rule screeners with adjudication (67 records assessed); every pooled number was extracted down a source ladder and verified against its committed source.

Results. Pooling 5 trials gave RR 0.82 (95% CI 0.65 to 1.03), random-effects (Paule-Mandel with a Hartung-Knapp interval). The 95% prediction interval was 0.65 to 1.03. 3 eligible trial(s) were declared absent for this outcome (reported reason on each).

Certainty. Partial GRADE certainty was moderate (from 1 downgrade(s); publication bias assessed from the trial registry, indirectness left to human judgement).

Methods

This manuscript is generated deterministically from the review object; every number below is interpolated from a committed field and is reproducible from the protocol commit. The protocol (SHA 17664842dc53) was committed before any synthesis ran. Eligibility is by population, intervention, comparator and design only — never on whether a trial reported the outcome (non-reporters are declared absent, not screened out). Two independently implemented rule screeners ran with adjudication. Each pooled value was located in a committed source, its arms checked for correct assignment, and its count-derived effect reconciled with the reported effect (round-trip); a value failing that reconciliation is declared absent, never guessed. Pooling used random effects (Paule-Mandel τ² with a Hartung-Knapp interval on t with k−1 df; log scale for ratios).

Results

Pooling 5 trials gave RR 0.82 (95% CI 0.65 to 1.03), random-effects (Paule-Mandel with a Hartung-Knapp interval). The 95% prediction interval was 0.65 to 1.03.

Risk-of-bias sensitivity. 3 of 5 pooled trials carry a risk-of-bias rating; no trial is rated high risk. Restricted to low-risk trials the estimate was RR 0.82 (95% CI 0.16 to 4.15, k=2); read the widened interval with the coverage caveat.

Limitations

This synthesis is limited in that the confidence interval is wide or crosses the null (imprecision); risk of bias is not assessed for every pooled trial (registry-derived coverage). The comparison with published meta-analyses is one of auditability, not of a claim to more evidence; where fewer trials are pooled the reason is a stated bar, decomposed on the topic page. Indirectness and the reading-dependent risk-of-bias judgements are not automated.

Data availability & reproduction

The committed cache, protocol (SHA 17664842dc53) and code regenerate this review byte-for-byte offline. Rebuild with a single command:

python scripts/build_topic.py colchicine-postop-af

Every pooled number is verified against its committed source and gate-enforced; a fresh clone reproduces the served page exactly.

Reporting (PRISMA)

Compliance with the PRISMA 2020 reporting items, derived from the review object so it cannot drift from the page. Every item is rendered or declared absent with a reason.

Reproducibility

Parity with the published comparator

Our pooled k = 5 vs the comparable same-scope comparator k = 7 — NEAR. Comparator (Zhao 2022) pools 9; comparable same-scope k=7 (excludes 2 post-PVI-ablation trials). Decomposed: 4 POOLED BY US (Bessissow 29237033, COPPS-2 25172965, END-AF 27502857, END-AF-low-dose 32720823) + END-AF recovered = 5 ours; of the rest: 2 SCOPE-excluded (Deftereos x2, post-pulmonary-vein-isolation ablation recurrence, not post-surgery POAF); 1 MULTI-ARM (Zarpelon 27223641, pre+post-op dosing + late-admission single-dose subgroup, dose/timing ambiguity); 1 REACH (Sarzaeem 2014, no PMID/not in corpus); 1 flagged ELIGIBLE but on verification NOT cleanly poolable (COPPS AF substudy 22090167: double-blind, real POAF 12.0% vs 22.0%, but the abstract gives percentages without exact per-arm N or a CI, and its PMC full text mis-maps — refuse on ambiguity). So the k gap is scope + multi-arm + reach + one percentage-only trial, not a search/extraction failure.

Independent second extraction (blind)

Of this page's pooled numbers, a blind second extractor agreed or reconciled on 3 of 3 that are checkable from the abstract (3 identical, 0 same-result-different-statistic, 0 conflict; 4 not stated in the abstract). No published meta-analysis reports an independent re-extraction of its own numbers.