Antiplatelet therapy after coronary artery bypass surgery: five year follow-up of randomised DACAB trial.
Zhu Y, Zhang W, Dimagli A, Han L, Cheng Z, Mei J, Chen X, Wang X, Zhou Y, Xue Q, Hu J, Tang M, Wang R, Song Y, Kang L, Redfors B, Gaudino M, Zhao Q
- DOI
- 10.1136/bmj-2023-075707
- Record issued
- 2026-08-16
- Engine
- 7.39.0
- Exported
- 2026-09-22
Prepared by Alpha1. This document is confidential: it is intended for the recipient it was shared with and must not be redistributed. The live record at alpha1science.com/verify/cbc57b8c-0009-419d-ad42-255baf69bf31 is authoritative.
How this rating was calculated
- IntegrityIntegrity concern−0.5★
- ReportingData & code availability partially met−0.25★
- No data or code availability links were detected to verify.
This Kaimen Rigor review uses Kaimen Rigor reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.
This is a well-conducted and clearly reported five-year follow-up of a randomized controlled trial, with strong methodology, ethical compliance, and transparent reporting. The main weakness is the absence of a data availability statement, which limits reproducibility. Minor copyedit issues and a few reporting gaps (e.g., no explicit reporting guideline) are present but do not undermine the scientific integrity.
Both reviewers classified the study as interventional, and I adopted that. The evaluation covered all eight dimensions; several sub-criteria were not applicable (e.g., animal housing, cell line authentication) due to the human clinical trial nature. The statistics verification covered only a subset of reported tests (6 of many), so the absence of flagged errors does not confirm all statistics.
Numerical inconsistencies
1 finding · worst lowValues that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.
- Internal contradictions in the reported numbersAssessed
Recomputed 6 tests: 6 consistent, 0 inconsistent; 1 recomputed directly from the reported test statistics, 5 via agent-written checks.
- CONSISTENTreported p = .040 · recomputed p = .043Recomputed hazard ratio 0.65 (95% CI 0.43–0.99), reported p=0.04
“hazard ratio 0.65, 95% confidence interval 0.43 to 0.99; P=0.04”
Taken as given: 0.43–0.99 is a two-sided 95% confidence interval for the hazard ratio of 0.65, not a range, an IQR, or a different interval level; the hazard ratio is a RATIO measure, so the interval is symmetric on the log scale; p=0.04 is the p for THIS estimate, not for another comparison in the same sentenceMethod: back the two-tailed p out of the log-scale CI width and compare it against the printed pHow we recomputed it: pCI(0.65, 0.43, 0.99, 1) - CONSISTENTreported p = .040 · recomputed p = .043Reviewer 1Primary MACE comparison: Ticagrelor+aspirin vs aspirin monotherapy
“hazard ratio 0.65, 95% confidence interval 0.43 to 0.99; P=0.04”
Taken as given: The hazard ratio is 0.65 with 95% CI 0.43 to 0.99.; The CI is two-sided at 95%.; The p-value is two-tailed.Method: Recomputed p-value from the hazard ratio and its 95% confidence interval using the normal approximation for the log hazard ratio.How we recomputed it: pCI(0.65, 0.43, 0.99, 1) - CONSISTENTreported p = .050 · recomputed p = .047Reviewer 1Primary MACE comparison: Ticagrelor+aspirin vs ticagrelor monotherapy
“hazard ratio 0.66, 95% confidence interval 0.44 to 1.00; P=0.05”
Taken as given: The hazard ratio is 0.66 with 95% CI 0.44 to 1.00.; The CI is two-sided at 95%.; The p-value is two-tailed.Method: Recomputed p-value from the hazard ratio and its 95% confidence interval using the normal approximation for the log hazard ratio.How we recomputed it: pCI(0.66, 0.44, 1.00, 1) - CONSISTENTreported p = .970 · recomputed p = .958Reviewer 1Primary MACE comparison: Ticagrelor monotherapy vs aspirin monotherapy
“hazard ratio 0.99, 95% confidence interval 0.68 to 1.44; P=0.97”
Taken as given: The hazard ratio is 0.99 with 95% CI 0.68 to 1.44.; The CI is two-sided at 95%.; The p-value is two-tailed.Method: Recomputed p-value from the hazard ratio and its 95% confidence interval using the normal approximation for the log hazard ratio.How we recomputed it: pCI(0.99, 0.68, 1.44, 1) - CONSISTENTreported p = .050 · recomputed p = .047Reviewer 2Check p-value for MACE comparison (T+A vs ticagrelor) from HR and CI.
“hazard ratio 0.66, 95% confidence interval 0.44 to 1.00; P=0.05”
Taken as given: The HR is 0.66 with 95% CI 0.44 to 1.00.; The CI is two-sided at 95%.; The p-value is two-tailed.Method: Recomputed p from HR and CI using the normal approximation for the log hazard ratio.How we recomputed it: pCI(0.66, 0.44, 1.00, 1) - CONSISTENTreported p = .970 · recomputed p = .958Reviewer 2Check p-value for MACE comparison (ticagrelor vs aspirin) from HR and CI.
“hazard ratio 0.99, 95% confidence interval 0.68 to 1.44; P=0.97”
Taken as given: The HR is 0.99 with 95% CI 0.68 to 1.44.; The CI is two-sided at 95%.; The p-value is two-tailed.Method: Recomputed p from HR and CI using the normal approximation for the log hazard ratio.How we recomputed it: pCI(0.99, 0.68, 1.44, 1)
- lowinternal contradictionThe abstract reports 148 MACE events, but the sum of events in the three groups (39+54+55=148) is consistent. However, the cumulative incidence percentages (22.6%, 32.9%, 29.9%) do not exactly match the event counts divided by group sizes (39/168=23.2%, 54/166=32.5%, 55/166=33.1%). This is likely due to censoring and time-to-event analysis, so not a true contradiction.
“148 patients had major adverse cardiovascular events, including 39 in the dual antiplatelet therapy group, 54 in the ticagrelor monotherapy group, and 55 in the aspirin monotherapy group.”
AbstractFind in source
Overstated conclusions
1 finding · worst lowConclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.
- Conclusions only partially backed by the presented evidenceAssessed
4 major claims checked against the paper's own evidence: 1 only partially supported (evidence backs part of the claim; gaps or caveats remain); the rest adequately supported.
- partialReviewers 1, 2The beneficial effect of ticagrelor dual antiplatelet therapy seemed to continue after the first year.The landmark analysis for years 2-5 showed a numerically lower risk but not statistically significant (HR 0.76, 95% CI 0.43-1.34, P=0.34). The claim is supported by the direction of effect but not by statistical significance.Evidence: Landmark analysis results in Sensitivity analyses.
“The beneficial effect of ticagrelor dual antiplatelet therapy seemed to continue after the first year”
Discussion ¶1Find in source - supportedReviewers 1, 2Treatment with ticagrelor dual antiplatelet therapy for one year after surgery reduced the risk of major adverse cardiovascular events at five years after coronary artery bypass grafting compared with aspirin monotherapy or ticagrelor monotherapy.The primary outcome analysis shows a statistically significant reduction in MACE for dual antiplatelet therapy vs aspirin monotherapy (HR 0.65, 95% CI 0.43-0.99, P=0.04) and vs ticagrelor monotherapy (HR 0.66, 95% CI 0.44-1.00, P=0.05). The results are consistent across sensitivity analyses.Evidence: Primary outcome results in Table 3 and sensitivity analyses.
“Treatment with ticagrelor dual antiplatelet therapy for one year after surgery reduced the risk of major adverse cardiovascular events at five years after coronary artery bypass grafting compared with aspirin monotherapy or ticagrelor monotherapy.”
ConclusionFind in source - supportedReviewer 1The increased incidence of mortality in the dual antiplatelet therapy group was based on a low number of events and was not accompanied by an increase in bleeding events.The paper reports numerically higher all-cause mortality in the DAPT group (9.3% vs 6.2% and 6.3%) but the difference is not statistically significant. Major bleeding rates were not significantly different. The claim is consistent with the presented data.Evidence: Table 2 and safety outcomes.
“We observed an absolute increase in mortality in patients who received dual antiplatelet therapy. This increased incidence of mortality was based on a low number of events and was not accompanied by an increase in bleeding events; further investigation is needed.”
DiscussionFind in source - supportedReviewer 2The DACAB-FE study provides evidence of a significant five year clinical benefit of one year of ticagrelor dual antiplatelet therapy after coronary artery bypass grafting compared with aspirin monotherapy or ticagrelor monotherapy.The primary outcome and sensitivity analyses support a significant benefit for the primary composite outcome, though the effect on individual outcomes like mortality was not significant.Evidence: Primary outcome results and sensitivity analyses.
“The DACAB-FE study provides evidence of a significant five year clinical benefit of one year of ticagrelor dual antiplatelet therapy after coronary artery bypass grafting compared with aspirin monotherapy or ticagrelor monotherapy.”
ConclusionFind in source
Efficacy claim is anchored to an adequate endpoint and a meaningful effect.
- ADEQUATESurrogate endpointThe primary outcome is a composite of hard clinical events (all-cause death, myocardial infarction, stroke, coronary revascularisation), not a surrogate. The efficacy claim is based on this clinical composite.
“The primary outcome was major adverse cardiovascular events (a composite of all cause death, myocardial infarction, stroke, and coronary revascularisation)”
- ADEQUATEEffect sizeThe effect size is reported as a hazard ratio of 0.65 (95% CI 0.43 to 0.99) for MACE with dual antiplatelet therapy versus aspirin monotherapy, with absolute risk reduction from 29.9% to 22.6% at five years. This is a clinically meaningful reduction in a hard outcome, and the result is statistically significant.
“Risk of major adverse cardiovascular events at five years was significantly lower with dual antiplatelet therapy versus aspirin monotherapy (22.6% v 29.9%; hazard ratio 0.65, 95% confidence interval 0.43 to 0.99; P=0.04)”
Data authenticity concerns
None foundAn adversarial read for patterns associated with data that may not be genuine: results that look too clean, implausibly large effects, duplicated data or images, and methods that do not match the results reported.
Checked — nothing surfaced.
Reporting gaps
1 finding · worst mediumRequired detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.
- Data/code availability incompleteAssessed
The introduction cites prior randomized and observational studies suggesting dual antiplatelet therapy is more effective than aspirin monotherapy for vein graft patency, but notes inconclusive evidence on clinical outcomes. The rationale for the DACAB-FE study is clearly linked to the need to assess long-term clinical outcomes. Limitations of prior work are implicitly addressed by the design of the DACAB trial and the extended follow-up.
“Findings from randomised and observational studies suggest that dual antiplatelet therapy is more effective than aspirin monotherapy in preventing saphenous vein graft failure.”
“We have now extended the clinical follow-up of patients included in the DACAB trial to five years (DACAB-Follow-up Extension (DACAB-FE) study), with the aim of investigating the effect of different antiplatelet strategies on clinical outcomes at five years after coronary artery bypass grafting.”
“However, the evidence is inconclusive with regard to the effect of dual antiplatelet therapy on clinical outcomes”
“Findings from randomised and observational studies suggest that dual antiplatelet therapy is more effective than aspirin monotherapy in preventing saphenous vein graft failure.”
“We have now extended the clinical follow-up of patients included in the DACAB trial to five years (DACAB-Follow-up Extension (DACAB-FE) study), with the aim of investigating the effect of different antiplatelet strategies on clinical outcomes at five years after coronary artery bypass grafting.”
The original DACAB trial was randomized 1:1:1 with an open-label, evaluator-blind design. The follow-up study uses intention-to-treat analysis, pre-specified outcomes, and multiple sensitivity analyses. The sample size was based on the original trial's power calculation, and the follow-up did not perform a new power calculation, which is acceptable for a follow-up study.
“randomised 1:1:1 to ticagrelor 90 mg twice daily plus aspirin 100 mg once daily (dual antiplatelet therapy), ticagrelor monotherapy 90 mg twice daily, or aspirin monotherapy 100 mg once daily”
“open label, evaluator blind, randomised, controlled trial”
“For the DACAB-FE study, we did no formal power calculation.”
“eligible patients were enrolled from 31 July 2014 through 3 November 2015 and randomised 1:1:1 to ticagrelor 90 mg twice daily plus aspirin 100 mg once daily (dual antiplatelet therapy), ticagrelor monotherapy 90 mg twice daily, or aspirin monotherapy 100 mg once daily for one year after coronary artery bypass graft surgery.”
“The DACAB trial was a prospective, multicentre, open label, evaluator blind, randomised, controlled trial”
“The sample size for the DACAB trial was based on a calculated statistical power of 80% to detect a significant difference in the primary outcome of vein graft patency. For the DACAB-FE study, we did no formal power calculation.”
Sex is reported (81.8% male, 18.2% female). Age is reported as mean (SD). Demographics include body mass index, coronary syndrome status, medical history, and other characteristics. Since both sexes are enrolled, sex_justified is not applicable. Species/strain and housing conditions are not applicable for a human trial.
“Most of the patients enrolled were men (81.8%)”
“Mean (SD) age, years | 63.1 (8.2)”
“Most of the patients enrolled were men (81.8%), and the mean age was 63.1 years.”
“Mean (SD) age, years | 63.1 (8.2) | 63.0 (8.1) | 62.9 (8) | 63.5 (8.1)”
The protocol was approved by the institutional review board of Ruijin Hospital (KY-2019-49). Written informed consent was obtained from all patients. The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.
“The protocol for DACAB-FE (available as an online supplement) was reviewed and approved by the independent institutional review board of Ruijin Hospital Shanghai Jiao Tong University School of Medicine (KY-2019-49).”
“Written informed consent was obtained from all patients.”
“This study was conducted in accordance with the Declaration of Helsinki and Guidelines for Good Clinical Practice.”
“The protocol for DACAB-FE (available as an online supplement) was reviewed and approved by the independent institutional review board of Ruijin Hospital Shanghai Jiao Tong University School of Medicine (KY-2019-49).”
“Written informed consent was obtained from all patients.”
“This study was conducted in accordance with the Declaration of Helsinki and Guidelines for Good Clinical Practice.”
The study uses ticagrelor and aspirin as investigational products, which are identified with manufacturer (AstraZeneca) and dosing regimen. Statistical software (SAS 9.4) is identified. No antibodies, cell lines, or other bench reagents are used, so those criteria are not applicable.
“ticagrelor 90 mg twice daily plus aspirin 100 mg once daily (dual antiplatelet therapy; n=168), ticagrelor monotherapy 90 mg twice daily (n=166), or aspirin monotherapy 100 mg once daily (n=166)”
“We used SAS version 9.4 for statistical analyses.”
“AstraZeneca provided the study medication free of charge”
“ticagrelor 90 mg twice daily plus aspirin 100 mg once daily (dual antiplatelet therapy; n=168), ticagrelor monotherapy 90 mg twice daily (n=166), or aspirin monotherapy 100 mg once daily (n=166)”
“We used SAS version 9.4 for statistical analyses.”
The paper names the statistical tests (Cox regression, Fine-Gray, etc.), reports exact p-values and 95% confidence intervals, and identifies the software. The Cox proportional hazards assumption was tested. Data presentation includes Kaplan-Meier curves and per-group event counts. Mathematical plausibility checks were not performed due to the nature of the data (time-to-event, large N).
“We used Kaplan-Meier curves to describe the event-free survival in the groups and univariate Cox regression models to compare the risk of outcomes between treatment groups.”
“We tested the Cox proportionality assumption by means of scaled Schoenfeld residuals.”
“hazard ratio 0.65, 95% confidence interval 0.43 to 0.99; P=0.04”
“We used Kaplan-Meier curves to describe the event-free survival in the groups and univariate Cox regression models to compare the risk of outcomes between treatment groups.”
“hazard ratio 0.65, 95% confidence interval 0.43 to 0.99; P=0.04”
“The global Schoenfeld residuals test verified the Cox proportionality assumption (P=0.63).”
The paper does not include an explicit data availability statement in the text provided. The only mention is in the funding section, which does not specify data access. No repository deposit or accession numbers are mentioned. Since this is a clinical trial, patient-level data may be subject to controlled access, but no mechanism is described.
The trial is registered (NCT03987373). Methods are detailed enough for replication. Limitations are discussed in the Discussion. Conclusions are proportional to the evidence. Funding sources and competing interests are declared. No reporting guideline is explicitly mentioned, but the paper follows standard reporting for clinical trials.
“Trial registration NCT03987373”
“The main limitation is that the randomised allocation to antiplatelet therapy was for the first year only.”
“Funding: The DACAB and DACAB-FE studies were funded as an investigator initiated trial by AstraZeneca.”
“Trial registration NCT03987373ClinicalTrials.gov NCT03987373 .”
“Funding: The DACAB and DACAB-FE studies were funded as an investigator initiated trial by AstraZeneca.”
“The main limitation is that the randomised allocation to antiplatelet therapy was for the first year only.”
Registered (1 ID: ClinicalTrials.gov). No reporting guideline cited.
Broken references and links
None found · partly checkedReferences checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.
Nothing surfaced — but not everything feeding this category ran (missing: data/code link verification), so read this as a partial clean bill.
Checked 34 references by DOI: 34 verified.
Every extracted reference resolved against Crossref/OpenAlex with no retraction flags.
Copyediting
6 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 6 minor suggestions below.
6 copyedit issues flagged: mostly consistency, grammar, other.
- MINORconsistencyAbstract, Results“22.6% v 29.9%”→ Use 'vs' instead of 'v' for consistency with the rest of the text.The abbreviation 'v' is used in the abstract but 'vs' is used elsewhere.
- MINORgrammarDiscussion, Strengths and limitations“the intention-to-treat analysis is of principal interest for inference as it describes the practical consequences of the specific antiplatelet treatment over the first year (and collider stratification, confounding by indication, and unmeasured bias may be present in the as-treated analyses).”→ Consider rephrasing for clarity, as the parenthetical is long and complex.The sentence is grammatically correct but could be clearer.
- MINORotherTable 1 footnote“* Defined as systolic/diastolic blood pressure ≥140/90 mm Hg.”→ Ensure footnote markers are correctly placed in the table.The footnote markers are not visible in the text provided.
- MINORconsistencyAbstract“Trial registration NCT03987373ClinicalTrials.gov NCT03987373 .”→ Remove duplicate registration number and fix spacing.Registration number appears twice.
- MINORgrammarDiscussion“The change in antiplatelet treatment could be seen as an intercurrent event, and we presented the intention-to-treat analysis and two as-treated analyses to describe the effect of the interventions both from a treatment policy estimand perspective and from a hypothetical strategy perspective.”→ Consider splitting into two sentences for clarity.Long sentence.
- MINORclarityMethods, Statistical analysis“We used a univariate Cox regression model to analyse treatment effects in key patient subgroups (age group; sex; coronary syndrome status; history of myocardial infarction, hypertension, diabetes, hyperlipidaemia, and peripheral arterial disease; pump use; and bleeding risk based on the CRUSADE score).”→ Use commas instead of semicolons for readability.Semicolons may be stylistically heavy.
The published work is robust and methodologically sound; an informed reader should weigh the lack of a data availability statement and the absence of a formal power calculation for the follow-up as minor limitations. No erratum is warranted based on the evidence reviewed, but the authors should consider adding a data availability statement and clarifying the follow-up power analysis in any correction or re-analysis.
- 1.HIGHdata codeAdd a data availability statement in the Methods or a dedicated section, specifying how de-identified patient data can be accessed (e.g., via a data access committee or on reasonable request with conditions).The paper currently has no data availability statement, which is a reproducibility gap that readers and journals expect to be addressed.
- 2.HIGHdata codeConsider depositing the statistical analysis code (e.g., SAS scripts) in a public repository with a DOI to enhance reproducibility.Providing analysis code allows independent verification of the reported results and strengthens the paper's reproducibility.
- 3.MEDIUMreportingMention adherence to a reporting guideline such as CONSORT in the Methods or a footnote.Explicitly stating compliance with CONSORT improves transparency and helps readers assess reporting completeness.
- 4.MEDIUMrigorProvide a formal power calculation for the follow-up extension, even if post hoc, to justify the sample size for the primary outcome.The absence of a power calculation for the follow-up is a limitation that could be addressed to strengthen the study's design rationale.
- 5.MEDIUMrigorClarify the handling of missing data for patients lost to follow-up beyond the last visit date.Describing how missing data were handled (e.g., censoring, imputation) is important for interpreting the time-to-event analyses.
- 6.MEDIUMreportingInclude a statement on whether the study was registered prospectively and any deviations from the registered protocol.Transparency about registration timing and protocol deviations is important for assessing the risk of bias.
- 7.MEDIUMreportingProvide more detail on the randomization method (e.g., random number generator, allocation concealment) in the Methods.Detailed randomization procedures enhance the reproducibility and credibility of the trial design.
- 8.MEDIUMreportingInclude a statement on whether any analyses were pre-specified in a statistical analysis plan and whether post hoc analyses are clearly labeled as such.Distinguishing pre-specified from post hoc analyses is critical for interpreting the strength of the findings.
- 9.LOWcopyeditIn the Abstract, replace 'v' with 'vs' for consistency with the rest of the text.Consistent abbreviation usage improves readability and professionalism.
- 10.LOWcopyeditIn the Abstract, remove the duplicate trial registration number and fix spacing: 'Trial registration NCT03987373ClinicalTrials.gov NCT03987373 .'The duplicate registration number is a typographical error that should be corrected.
- 11.LOWcopyeditIn the Discussion, consider splitting long sentences (e.g., the one about intercurrent events and estimands) into two for clarity.Shorter sentences improve readability and reduce the risk of misinterpretation.
- 12.LOWcopyeditIn the Methods, Statistical analysis, use commas instead of semicolons in the subgroup list for readability.Commas are more conventional in lists and improve readability.
- 13.LOWcopyeditEnsure footnote markers in Table 1 are correctly placed and visible.Properly placed footnotes are essential for interpreting table data.
The star rating is the report’s one-glance summary. Every paper starts at 5★ and loses stars for the concrete problems the review finds — so a rating is never a vague average, it’s a running total you can read line by line under “How this rating was calculated.”
- Reporting — 8 dimensionseach dimension that fully fails−½★
- each dimension partially met−¼★
- Statistics · Integrity · Claimseach serious problem−1★
- each medium problem−½★
- Citationseach retracted or unverifiable reference−¼★
- Copyeditonly when the manuscript needs a full edit−½★
The rating never drops below 1★, and a demonstrable critical failure (an impossible statistic, a proven ethics violation) caps it at 1★ on its own — so the stars can never look healthy when the verdict is CRITICAL.
The rating draws on a panel of agents. Three independent Kaimen Rigor reviewers grade the eight dimensions below across several independent passes (the shown verdict is their majority vote — steadier than any single run), isolate the paper’s major claims and check its own evidence backs them, and flag integrity concerns. Alongside them, a citation agent resolves every reference against Crossref, OpenAlex, and Retraction Watch; a statistics agent recomputes reported tests; and rule-based checks verify that declared data/code links actually resolve. Full text is required — an abstract-only submission is not analyzed.
Graded against NIH, MDAR, ARRIVE 2.0, CONSORT, EQUATOR, and RRID guidelines. A dimension that doesn’t apply to the study type is skipped, never penalized.
This Kaimen Rigor review is model-assisted and is not a substitute for formal expert review. It complements human evaluation by surfacing potential methodological concerns — verify each finding against the source.