Fractional Flow Reserve-Guided Complete vs Culprit-Only Revascularization in Non-ST-Elevation Myocardial Infarction and Multivessel Disease: The SLIM Randomized Clinical Trial.
Pustjens TFS, Veenstra L, Camaro C, Ruiters AW, Lux Á, Ruzsa Z, Piroth Z, Ilhan M, Vainer J, Gho B, Winkler PJC, Stein M, Theunissen RALJ, Kala P, Polad J, Berta B, Gabrio A, van Royen N, van 't Hof AWJ, Rasoul S
- DOI
- 10.1001/jama.2025.16189
- Record issued
- 2026-08-15
- Engine
- 7.39.0
- Exported
- 2026-09-20
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/8362d1dd-6769-4ebc-9b60-c6f4c746d2c0 is authoritative.
How this rating was calculated
- IntegrityIntegrity concern ×3−1.5★
- 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 well-reported randomized clinical trial with a clear scientific premise, rigorous design, and transparent reporting. The main weakness is the vague data availability statement, which lacks concrete access details. Minor gaps include incomplete specification of some reagents and minor copyedit issues.
Both reviewers independently scored all eight dimensions and agreed on all statuses, so no divergence needed reconciliation. The study type is interventional (randomized controlled trial). Non-applicable sub-criteria (e.g., animal housing, cell line authentication) were excluded from scoring. The statistics verification covered only a subset of tests; the rest remain unverified but no errors were found.
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 3 tests: 3 consistent, 0 inconsistent; 3 via agent-written checks.
- CONSISTENTreported p = .003 · recomputed p = .003Reviewers 1, 2Primary outcome hazard ratio p-value from reported HR and 95% CI
“HR, 0.38 [95% CI, 0.20-0.72]; P = .003”
Taken as given: The HR is 0.38 and the 95% CI is 0.20 to 0.72.; The CI is two-sided at 95%.; The p-value is two-tailed.Method: Recomputed two-tailed 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(0.38, 0.20, 0.72, 1) - CONSISTENTreported p < .001 · recomputed p = <.001Reviewers 1, 2Any revascularization hazard ratio p-value from reported HR and 95% CI
“HR, 0.24 [95% CI, 0.11-0.56]; P < .001”
Taken as given: The HR is 0.24 and the 95% CI is 0.11 to 0.56.; The CI is two-sided at 95%.; The p-value is two-tailed.Method: Recomputed two-tailed 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(0.24, 0.11, 0.56, 1) - CONSISTENTreported p = .002 · recomputed p = .002Reviewers 1, 2Net adverse clinical events hazard ratio p-value from reported HR and 95% CI
“HR, 0.39 [95% CI, 0.21-0.70]; P = .002”
Taken as given: The HR is 0.39 and the 95% CI is 0.21 to 0.70.; The CI is two-sided at 95%.; The p-value is two-tailed.Method: Recomputed two-tailed 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(0.39, 0.21, 0.70, 1)
- lowinternal contradictionThe abstract reports 478 randomized patients, but the CONSORT diagram shows 478 randomized, which is consistent. However, the text states '5 withdrew consent and 2 did not meet the inclusion criteria' while the figure shows 4 withdrew consent in the complete group and 1 in the culprit-only group, totaling 5, and 2 enrolled inappropriately in the culprit-only group. This is consistent.
Of these patients, 5 withdrew consent and 2 did not meet the inclusion criteria (Figure 1).
Figure 1reviewer’s wording - lowinternal contradictionThe text states 'crossover occurring in 7 patients in the culprit-only group' and Figure 1 shows 7 protocol violations in the culprit-only group, but the figure also lists 3 received nonculprit PCI and 4 had negative FFR, which sums to 7. This is consistent.
“with crossover occurring in 7 patients in the culprit-only group”
Figure 1
Overstated conclusions
None foundConclusions 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.
Checked — nothing surfaced.
4 major claims checked against the paper's own evidence: all adequately supported.
- supportedReviewers 1, 2FFR-guided complete revascularization reduces the composite of all-cause death, nonfatal myocardial infarction, any revascularization, and stroke at 1 year compared with culprit-only revascularization.The primary outcome result directly supports this claim with a statistically significant hazard ratio.Evidence: Primary outcome: 13 (5.5%) vs 32 (13.6%); HR 0.38 (95% CI 0.20-0.72); P=.003.
“The primary outcome occurred in 13 patients (5.5%) in the FFR-guided complete revascularization group vs 32 patients (13.6%) in the culprit-only group (hazard ratio [HR], 0.38 [95% CI, 0.20-0.72]; P = .003).”
Abstract - supportedReviewer 1The reduction in the primary outcome is mainly driven by reduced repeat revascularization.The secondary outcome of any revascularization shows a significant reduction, while other components (death, MI, stroke) are not significantly different, supporting the claim.Evidence: Any revascularization: 7 (3.0%) vs 27 (11.5%); HR 0.24 (95% CI 0.11-0.56); P<.001. Other components not significant.
The benefit was mainly driven by reduced repeat revascularization procedures.
Discussion ¶1reviewer’s wording - supportedReviewers 1, 2FFR-guided complete revascularization is safe and feasible during the index procedure.The trial reports a slightly higher rate of PCI-related adverse events in the complete revascularization group, but these were not significantly different and the primary outcome was improved, supporting feasibility.Evidence: PCI-related adverse events: 10 (4.2%) vs 3 (1.3%) in Table 2.
A slightly higher occurrence of index PCI related adverse events was found in the complete revascularization group (10 [4.2%] vs 3 [1.3%]).
Resultsreviewer’s wording - supportedReviewer 2The benefit is mainly driven by reduced repeat revascularization.The secondary outcome of any revascularization shows a significant reduction, supporting this claim.Evidence: Any revascularization: 7 (3.0%) vs 27 (11.5%), HR 0.24 (95% CI 0.11-0.56), P<.001.
“Among the independent primary outcome components, a significant reduction of any revascularization was observed in the complete revascularization group (7 [3.0%] vs 27 [11.5%]; HR, 0.24 [95% CI, 0.11-0.56]).”
Results
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, nonfatal myocardial infarction, any revascularization, and stroke. These are clinical outcomes, not surrogate biomarkers. The intervention is a revascularization strategy, and the primary endpoint directly measures clinical events.
“The primary outcome was a composite of all-cause death, nonfatal myocardial infarction, any revascularization, and stroke at 1 year.”
- ADEQUATEEffect sizeThe primary outcome occurred in 5.5% of the complete revascularization group vs 13.6% in the culprit-only group, with an absolute risk reduction of 8.1% and a hazard ratio of 0.38 (95% CI, 0.20-0.72). This is a substantial reduction in a composite of hard clinical events, and the effect is statistically significant. The magnitude is clinically meaningful.
“The primary outcome occurred in 13 patients (5.5%) in the FFR-guided complete revascularization group vs 32 patients (13.6%) in the culprit-only group (hazard ratio [HR], 0.38 [95% CI, 0.20-0.72]; P = .003).”
Data authenticity concerns
1 finding · worst lowAn 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.
- Other integrity concernAssessed
3 integrity concerns flagged (0 high).
- lowotherThe trial was stopped early? No, it enrolled the planned sample size. The interim analysis adjusted the sample size, which is acceptable.
“After a prespecified interim analysis including 215 patients with 1-year follow-up data, the adjusted event rate in the control group was 10.52%.”
Methods
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 observational data and randomized trials (e.g., FIRE, SMILE) and notes the limitations of existing evidence, including reliance on visual assessment and mixed STEMI/NSTEMI populations. The rationale for using FFR-guided complete revascularization is clearly linked to the study objective. Limitations of prior research are addressed by the study design (e.g., broader NSTEMI population, FFR-guided approach).
“Therefore, this study aimed to investigate whether use of FFR-guided complete revascularization of all significant nonculprit lesions improved clinical outcomes compared with culprit-only revascularization during the index procedure in patients with NSTEMI and multivessel disease.”
“Therefore, this study aimed to investigate whether use of FFR-guided complete revascularization of all significant nonculprit lesions improved clinical outcomes compared with culprit-only revascularization during the index procedure in patients with NSTEMI and multivessel disease.”
Randomization method (computer-generated, block size 4) and unit (patient) are reported. Blinding is not possible due to the interventional nature, but the open-label design is acknowledged and outcome adjudication was blinded. A sample size calculation with updated event rate is provided. Inclusion/exclusion criteria are pre-specified. Outlier handling is not explicitly described, but the analysis population (as randomized) and per-protocol/as-treated analyses are defined. Controls are inherent in the comparator arm. Independent replication is not applicable for a single pivotal trial.
“eligible patients were randomized in a 1:1 ratio using a computer-generated online randomization tool to receive either immediate FFR-guided complete revascularization or culprit-only PCI, with a block size of 4.”
“Using this updated estimate, a sample size of 226 patients per group was needed to achieve 80% power with a 2-sided α of 5%.”
“eligible patients were randomized in a 1:1 ratio using a computer-generated online randomization tool to receive either immediate FFR-guided complete revascularization or culprit-only PCI, with a block size of 4.”
“Using this updated estimate, a sample size of 226 patients per group was needed to achieve 80% power with a 2-sided α of 5%.”
Sex is reported for all participants (72.9% male). Age and health status (comorbidities, GRACE score) are reported. Demographics include age, sex, and comorbidities; race/ethnicity is not reported, which is common in cardiovascular trials. Species/strain and housing conditions are not applicable for a human trial.
“the majority of patients were male (347 [72.9%])”
“The mean (SD) age was 65.9 years (10.6)”
“Diabetes 65 (27.3) 41 (17.2)”
“the majority of patients were male (347 [72.9%])”
“The mean (SD) age was 65.9 years (10.6)”
“Diabetes 65 (27.3) 41 (17.2)”
The protocol was approved by a named ethics committee (medical ethical committee of the Zuyderland Medical Center, protocol number 17-T-142). Informed consent was obtained orally in the presence of an independent third person and subsequently in writing. Regulatory compliance is implied by adherence to CONSORT and the Declaration of Helsinki is not explicitly named, but the approval statement is sufficient.
The trial uses everolimus-eluting stents (Xience) as the preferred stent, which is named with manufacturer. FFR wires and adenosine are mentioned but not fully specified (vendor/catalog not given), which is a minor gap. Statistical software (SPSS version 29.0) is identified. No antibodies, cell lines, or mycoplasma testing are applicable.
“All analyses were performed with SPSS version 29.0 (IBM).”
“All analyses were performed with SPSS version 29.0 (IBM).”
All statistical tests are named (t-test, Mann-Whitney U, chi-square, Fisher exact, Cox proportional hazards, log-rank). Assumptions are handled by design (e.g., non-Gaussian distributions use non-parametric tests). Exact p-values are reported for primary and key secondary outcomes. Effect sizes with 95% CIs are provided. Software is identified. Data presentation includes Kaplan-Meier curves and per-group n. Mathematical plausibility checks were not performed due to lack of raw data, but no obvious inconsistencies were noted.
“Baseline variables with non-Gaussian distributions were analyzed using the Mann-Whitney U test and summarized as median (IQR).”
“0.38 (0.20 to 0.72)”
“0.38 (0.20 to 0.72)”
The paper states 'Data Sharing Statement: See Supplement 3.' The content of Supplement 3 is not available in the provided text, so the concreteness of the access route cannot be verified. No repository deposit or accession numbers are mentioned. Code sharing is not applicable as no custom code is described.
“Data Sharing Statement: See Supplement 3.”
“Data Sharing Statement: See Supplement 3.”
The trial is registered (NCT03562572). CONSORT reporting guideline is followed. All pre-specified outcomes are reported, including non-significant ones. Limitations are explicitly discussed. Conclusions are proportional to the evidence. Funding and conflicts of interest are disclosed.
“TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03562572”
“TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03562572”
Registered (1 ID: ClinicalTrials.gov). Reporting guideline cited: CONSORT.
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 47 references by DOI: 46 verified — 1 no DOI (shown, not verified).
- NO DOIThe SYNTAX Score: an angiographic tool grading the complexity of coronary artery diseaseNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
Copyediting
3 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 3 minor suggestions below.
3 copyedit issues flagged: mostly consistency, typo.
- MINORtypoTable 2, header“Circumflex artery, No. (%), No. (%)”→ Remove duplicate 'No. (%)'Duplicate text in table header.
- MINORconsistencyResults, Primary and Secondary Outcomes“P = .003”→ Ensure p-values are consistently formatted (e.g., P vs p).Inconsistent capitalization of p-value.
- MINORconsistencyResults, Primary and Secondary Outcomes“P = .003”→ Ensure p-values are consistently formatted (e.g., P = .003 vs P < .001).Minor inconsistency in p-value formatting.
The published work is robust and well-reported, with only minor reporting gaps. An informed reader should weigh the vague data availability statement and the incomplete specification of FFR wires/adenosine as minor limitations. No erratum or re-analysis is warranted based on the evidence reviewed.
- 1.HIGHdata codeIn the Article Information section, replace the vague 'Data Sharing Statement: See Supplement 3' with a detailed statement specifying the access mechanism (e.g., data access committee, contact, conditions) and any repository or DOI.A data sharing statement that merely points to a supplement without specifying access details is inadequate for a data-driven clinical trial and undermines reproducibility.
- 2.MEDIUMrigorIn the Methods section (FFR Management), specify the vendor and catalog numbers for the FFR wire and adenosine used in the study.Full identification of key reagents is necessary for reproducibility and is a standard expectation for interventional trials.
- 3.MEDIUMreportingIn the Methods section, explicitly state that the study was conducted in accordance with the Declaration of Helsinki or other relevant ethical standards.While ethics approval is documented, explicitly naming the ethical standard strengthens the ethics reporting.
- 4.MEDIUMreportingIn the Results section (Baseline Characteristics), consider adding a statement about race/ethnicity if data are available, or note their absence.Reporting race/ethnicity enhances generalizability assessment, though its absence is common in cardiovascular trials.
- 5.MEDIUMdata codeIf applicable, deposit de-identified aggregate data or statistical analysis code in a public repository with a DOI, and reference it in the data availability statement.Public data/code deposition would enhance reproducibility and move data_code_availability toward pass.
- 6.LOWcopyeditIn Table 2 header, remove the duplicate 'No. (%)' text.The duplicate text is a minor typo that should be corrected for professionalism.
- 7.LOWcopyeditIn the Results section, standardize p-value formatting (e.g., use 'P' consistently and format as 'P = .003' or 'P < .001' consistently).Consistent formatting of p-values improves readability and avoids minor inconsistencies.
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★
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