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Systematic Review | Volume 18 Issue 10 (OCTOBER, 2026) | Pages 43 - 52
Intravascular Imaging-Guided Versus Angiography-Guided Percutaneous Coronary Intervention in Acute Coronary Syndromes: Cardiovascular and Renal Outcomes from a Systematic Review and Meta-analysis of Randomized Controlled Trials
 ,
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 ,
 ,
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1
Final-Year Medical Student, LUMHS, Jamshoro USMLE Aspirant Aspiring Internal Medicine Resident
2
People’s University of Medical and Health Sciences for Women, Nawabshah, Sindh, Pakistan PLAB 1 and 2 Cleared
3
MBBS, BSc, FCPS (Nephrology) King Edward Medical University
4
FCPS (Haematology) Bolan University of Medical and Health Sciences, Quetta
5
Ziauddin University
6
Ziauddin Medical College
Under a Creative Commons license
Open Access
Received
Aug. 21, 2026
Revised
Sept. 9, 2026
Accepted
Sept. 22, 2026
Published
Oct. 7, 2026
Abstract

Objective: To compare cardiovascular outcomes and renal safety of intravascular imaging-guided versus angiography-guided percutaneous coronary intervention (PCI) in acute coronary syndromes (ACS). Study Design: Systematic review with aggregate-data meta-analysis of randomized controlled trials and separately extractable randomized ACS subgroups. Place and Duration of Study: Global published evidence searched through 6 October 2026. Methodology: A reproducible PubMed search and targeted citation retrieval identified ACS-specific trial evidence. Compatible target-vessel failure (TVF) hazard ratios were pooled using inverse-variance random-effects analysis. Broader composite outcomes and differently defined kidney-injury events were examined separately. Conservative modified Hartung–Knapp intervals tested small-study uncertainty.

Results: Ten trial cohorts comprised 7,229 randomized ACS participants. Two compatible TVF cohorts included 4,337 participants: pooled HR 0.61 (95% CI 0.46–0.80; p=0.00046; I²=17.8%). The conservative interval was 0.10–3.67. Adding the broader OCCUPI ACS composite gave HR 0.59 (95% CI 0.47–0.73; I²=0%). Exploratory pooling of two differently defined renal endpoints in 1,072 participants gave RR 0.80 (95% CI 0.35–1.87; p=0.611). Conclusion: Imaging guidance supported lower cardiovascular event risk in selected ACS patients. Renal benefit remained uncertain. Sparse compatible trials and subgroup evidence require cautious interpretation.

Keywords
INTRODUCTION

Acute coronary syndromes require timely restoration of coronary blood flow and durable treatment of the culprit lesion. Angiography identifies stenosis and guides device delivery but principally depicts the vessel lumen. It cannot reliably define the vessel wall or every mechanism of an unsatisfactory stent result.

 

The 2025 American guideline recommends intracoronary imaging for procedural guidance in ACS patients undergoing stenting of left main or complex lesions. This recommendation concerns prevention of ischaemic events and does not establish a direct renal benefit. [1]

 

European guidance similarly places intravascular imaging within contemporary ACS management. Treatment decisions still depend on haemodynamic stability, lesion anatomy and the urgency of reperfusion. Imaging should answer a procedural question rather than become an isolated technical exercise. The 2023 European guideline and the 2024 Japanese procedural consensus describe its role in assessing lesion preparation and stent optimisation. Their recommendations provide a clinical framework for interpreting randomized comparisons without assuming that all ACS presentations respond identically. [2,3]

 

Recent randomized studies have strengthened the general imaging evidence but have not uniformly demonstrated benefit. ILUMIEN IV improved minimum stent area with optical coherence tomography (OCT) without a significant reduction in its primary target-vessel failure endpoint. OCTOBER supported OCT guidance in complex bifurcations.

 

RENOVATE-COMPLEX-PCI and OCCUPI reported favourable outcomes in complex lesions using imaging-based strategies. These trials enrolled mixed clinical presentations. Their overall populations therefore cannot automatically be treated as ACS populations in a condition-specific meta-analysis. [4–7]

 

Imaging modality and kidney function further complicate interpretation. OCTIVUS and OPINION ACS compared two imaging modalities rather than imaging against angiography. They answer a different question and cannot supply the comparator required here. A RENOVATE kidney-disease substudy examined cardiovascular outcomes in patients with chronic kidney disease but did not equate improved cardiovascular prognosis with preserved renal function. More recent IVUS-CHIP and DKCRUSH VIII results also differed across complex-lesion settings.

 

An updated network synthesis supports imaging in broader PCI populations yet leaves the need for an ACS-specific renal assessment. This review therefore examined separately extractable randomized ACS evidence, prioritised comparable cardiovascular endpoints and evaluated renal events without substituting contrast exposure for kidney injury. [8–13]

MATERIAL AND METHODS

Review Design and Eligibility The review used PRISMA 2020 reporting principles to describe identification, selection and synthesis. No prospective protocol registration was available. The population comprised adults with ACS undergoing a coronary intervention. The intervention was an imaging-guided strategy using intravascular ultrasound (IVUS), OCT or multimodality imaging. The comparator was angiography-guided management. Dedicated ACS trials and randomized ACS subgroups were eligible when their results could be verified separately. Trials of stent selection or drug treatment with imaging used only for measurement were excluded. Imaging-versus-imaging trials, nonrandomized comparisons and duplicated subgroup publications were not treated as independent intervention cohorts. [14] Search and Report Selection PubMed was searched on 6 October 2026 from database inception. The query combined “intravascular ultrasound” OR “optical coherence tomography” OR “intravascular imaging” with randomized OR randomised, “coronary intervention” OR PCI and “acute coronary” OR “myocardial infarction” OR NSTEMI OR STEMI. All terms were searched in title/abstract fields. Publication dates were restricted through the search date. The query returned 353 records. Targeted citation retrieval added the ULTIMATE ACS report. Trial acronyms and bibliographies were checked against primary reports. Scopus, Embase and Web of Science were not directly searched. The archived query, PMID list and selection log preserved the actual retrieval process. Selection and Extraction Titles and abstracts were assessed against the population, randomized intervention and comparator criteria. Twenty-four candidate reports were examined using abstracts and accessible full reports or investigator presentations. This was an access-limited evidence assessment rather than a claim that every candidate full text was obtained. Ten distinct ACS trial cohorts were retained. Fourteen candidate reports were excluded: six lacked sufficiently extractable ACS-specific primary-report data, three duplicated trial populations, two compared imaging modalities, two were nonrandomized and one was a protocol. Numerical extraction retained randomized denominators, endpoint definitions, follow-up and published effect estimates. Counts were distinguished from Kaplan–Meier percentages. No patient-level data were reconstructed and no study-selection counts were estimated. Outcomes and Appraisal The primary cardiovascular endpoint was TVF comprising cardiac death, target-vessel myocardial infarction and clinically driven target-vessel revascularisation. A separate exploratory analysis admitted the broader OCCUPI composite that also included stent thrombosis and any myocardial infarction. Secondary outcomes were component cardiovascular events and trial-defined acute kidney injury or contrast-induced nephropathy. Contrast volume remained a procedural exposure. Risk-of-bias considerations followed the RoB 2 domains of randomization, deviations, missing outcomes, measurement and selective reporting. Appraisal was limited to available reporting. Independent duplicate screening and a completed author-verified domain assessment were not claimed. Subgroup selection and secondary endpoint multiplicity were treated as additional interpretive concerns. [15] Statistical Analysis Published hazard ratios were analysed on the logarithmic scale. Standard errors were calculated from the reported 95% confidence intervals using their logarithmic width divided by 3.9199. An inverse-variance random-effects model used the DerSimonian–Laird between-study variance estimator. Heterogeneity was described by Q, I² and τ². A modified Hartung–Knapp sensitivity interval used a t distribution with k−1 degrees of freedom and a variance multiplier bounded below by one. This conservative approach explicitly addressed the instability of two-study pooling. A fixed-effect sensitivity estimate and a one-year broader-composite analysis were also calculated. Different follow-up durations were not converted into artificial one-year event counts. Renal Synthesis and Reproducibility Renal risk ratios were calculated from verified event counts and randomized group sizes. Only the RENOVATE ACS subgroup and DOCTORS supplied directly checkable paired counts for this exploratory synthesis. Their kidney-injury definitions differed, so the combined estimate was designated exploratory and accompanied by separate trial results. No renal noninferiority margin was specified. Dialysis and longer-term kidney outcomes were not inferred from creatinine-based short-term endpoints. Analyses were performed in Python with NumPy and SciPy. Two-sided p<0.05 described conventional statistical significance without resolving clinical importance or reporting limitations. Funnel plots, meta-regression and publication-bias tests were omitted because too few compatible cohorts were available. Ethical Considerations The analysis used published aggregate results and did not recruit participants or access identifiable clinical records. No new institutional approval or consent procedure was asserted. Eligibility and modelling decisions were documented for reproducibility. Trial reports remained the authority for their individual ethics approvals. The review did not establish that the listed authors independently screened records or performed the original clinical trials.

RESULT

The documented retrieval comprised 354 unique records after the supplementary ULTIMATE report was added. Of these, 330 were excluded before candidate assessment. Ten retained cohorts represented 7,229 randomized ACS participants. This total included the randomized EROSION III population rather than its smaller per-protocol population. Participants were counted once per trial. Two cohorts provided compatible TVF hazard ratios for the primary synthesis. A third provided a broader ACS cardiovascular composite. Several smaller randomized trials contributed mechanistic or procedural findings rather than interchangeable clinical endpoints. Figure 1 shows the documented selection and synthesis pathway.

IVUS-ACS randomized 3,505 participants across centres in China, Pakistan, Italy and the United Kingdom. At one year, TVF occurred in 70/1,753 patients assigned to IVUS and 128/1,752 assigned to angiography. The published Kaplan–Meier rates were 4.0% and 7.3% with HR 0.55 (95% CI 0.41–0.74; p=0.0001). In the RENOVATE ACS subgroup, 560 participants received imaging-guided PCI and 272 received angiography-guided PCI. Reported TVF estimates were 10.4% versus 14.6% with HR 0.74 (95% CI 0.48–1.15; p=0.18) over median 2.1-year follow-up. [16,17]

 

The primary random-effects synthesis of these 4,337 participants produced HR 0.61 (95% CI 0.46–0.80; p=0.00046). Heterogeneity was I²=17.8%, Q=1.22 and τ²=0.00784. The fixed-effect sensitivity estimate was HR 0.60 (95% CI 0.47–0.77). The modified Hartung–Knapp interval widened to 0.10–3.67. Thus conventional and conservative intervals differed materially despite the same pooled point estimate. Exploratory component estimates were HR 0.45 (95% CI 0.24–0.84) for cardiac death, 0.79 (0.46–1.37) for target-vessel myocardial infarction and 0.53 (0.33–0.86) for target-vessel revascularisation. These comparisons used only two cohorts and were not adjusted for multiplicity.

 

The OCCUPI ACS analysis included 790 participants. Its one-year composite occurred at reported rates of 4.9% with OCT and 9.5% with angiography: HR 0.50 (95% CI 0.29–0.87; p=0.011). Adding this broader endpoint to the two TVF cohorts produced HR 0.59 (95% CI 0.47–0.73; p<0.00001; I²=0%). Its modified Hartung–Knapp interval was 0.36–0.96. Restricting the broader synthesis to the two one-year reports gave HR 0.54 (95% CI 0.42–0.70). These estimates were sensitivity results because endpoint composition and subgroup design differed. Table II and Figure 2 distinguish the primary and exploratory analyses. [18]

 

In DOCTORS, 240 patients with non-ST-elevation ACS were randomized equally between OCT and angiography. Post-PCI fractional flow reserve was 0.94 ± 0.04 versus 0.92 ± 0.05 (p=0.005). Acute kidney injury occurred in two patients per group, reported as 1.6% in each arm. The RENOVATE ACS report recorded contrast-induced nephropathy in 11/560 versus 7/272 patients. Exploratory pooling of these 22 events in 1,072 participants gave RR 0.80 (95% CI 0.35–1.87; p=0.611; I²=0%). The conservative interval was extremely wide. The trial-specific renal definitions and procedural findings appear in Table III. [19]

 

OCTACS randomized 100 NSTEMI patients and found less uncovered stent strut burden at six months with OCT guidance. ROBUST randomized 201 STEMI patients and demonstrated improved imaging-derived stenosis outcomes without a significant difference in nine-month major adverse events. HONEST randomized 75 NSTEMI patients receiving magnesium bioresorbable scaffolds and found similar six-month healing-stage results between guidance strategies. These surrogate outcomes were not combined with TVF. EROSION III randomized 246 patients with early infarct-artery patency; its per-protocol comparison showed fewer stent implantations with OCT but similar one-year cardiocerebrovascular event rates. [20–23]

 

NIRVUS randomized 104 myocardial-infarction patients to multimodality imaging or angiographic guidance. Imaging increased minimum stent area and six-month strut coverage but its principal endpoint was vascular healing. The ULTIMATE ACS report contributed 1,136 participants with three-year TVF counts of 43/569 versus 66/567 (log-rank p=0.019). Its longer follow-up and absence of a directly extractable ACS hazard ratio in the accessible abstract prevented inclusion in the hazard-ratio pool. It remained part of the qualitative cardiovascular synthesis. Baseline characteristics and outcome availability are summarised in Table I. [24,25]

 

Figure 1: Documented search and synthesis flow

Candidate assessment included abstracts and accessible primary reporting. The flow does not imply that 24 full-text reports were retrieved.

 

Table I: Characteristics and outcome availability of included randomized ACS cohorts

Trial / cohort

Randomized ACS population

Setting and follow-up

Outcome contribution

IVUS-ACS

3,505; IVUS 1,753 / angiography 1,752

Multinational; ACS; 1 year

TVF

RENOVATE ACS

832; imaging 560 / angiography 272

Korea; prespecified ACS subgroup; median 2.1 years

TVF and renal events

OCCUPI ACS

790; randomized ACS subgroup

Korea; post hoc ACS subgroup; 1 year

Broader MACE

DOCTORS

240; OCT 120 / angiography 120

France; NSTE-ACS; procedural / 6 months

Post-PCI FFR and AKI

OCTACS

100; OCT 50 / angiography 50

Denmark; NSTEMI; 6 months

Strut coverage

ROBUST

201; OCT 105 / angiography 96

STEMI; 9 months

Imaging endpoints and MACE

HONEST

75; randomized 1:1

NSTEMI; magnesium scaffolds; 6 months

Healing stage

EROSION III

246 randomized; 226 per protocol

STEMI with early artery patency; 1 year

Stent use and clinical events

NIRVUS

104 randomized

Acute MI; multimodality imaging; 6 months

Strut coverage

ULTIMATE ACS

1,136; IVUS 569 / angiography 567

China; ACS subgroup; 3 years

TVF counts; qualitative synthesis

ACS: acute coronary syndrome; FFR: fractional flow reserve; MI: myocardial infarction; NSTE-ACS: non-ST-elevation ACS; TVF: target-vessel failure. Cohort total excludes stable-disease participants and avoids duplicated secondary reports.

 

Table II: Primary cardiovascular estimates and exploratory analyses

Outcome / analysis

Cohorts / n

Effect (95% CI)

p-value; I²

TVF, primary

2 / 4,337

HR 0.61 (0.46–0.80)

0.00046; 17.8%

TVF, conservative sensitivity

2 / 4,337

HR 0.61 (0.10–3.67)

Modified Hartung–Knapp

Cardiac death, exploratory

2 / 4,337

HR 0.45 (0.24–0.84)

0.011; 0%

Target-vessel MI, exploratory

2 / 4,337

HR 0.79 (0.46–1.37)

0.401; 55.8%

Target-vessel revascularisation, exploratory

2 / 4,337

HR 0.53 (0.33–0.86)

0.0099; 25.8%

Broader composite sensitivity

3 / 5,127

HR 0.59 (0.47–0.73)

<0.00001; 0%

Broader composite, conservative

3 / 5,127

HR 0.59 (0.36–0.96)

Modified Hartung–Knapp

Kidney injury, exploratory

2 / 1,072

RR 0.80 (0.35–1.87)

0.611; 0%

Primary TVF: IVUS-ACS and RENOVATE ACS. Broader composite adds OCCUPI ACS and is not an identical endpoint. Component comparisons are exploratory. Conservative intervals widen materially with only two cohorts.

 

Figure 2: Cardiovascular and renal forest plots

Diamonds show conventional random-effects estimates. Cardiovascular and renal effect measures differ. Conservative primary TVF interval: 0.10–3.67. Renal pooling is exploratory because definitions differ.

 

 

 

Table III: Renal events, definitions and contrast exposure

Evidence

Imaging vs angiography

Renal definition / scope

Procedural exposure / interpretation

RENOVATE ACS

11/560 (2.0%) vs 7/272 (2.6%)

Creatinine rise ≥0.5 mg/dL or ≥25% within 48–72 hours

Contrast: 198.8 ± 127.8 vs 198.3 ± 121.6 mL; p=0.96

DOCTORS

2/120 (1.6%) vs 2/120 (1.6%)

Absolute creatinine rise 0.5 mg/dL from baseline

Contrast: median 190 (IQR 140–250) vs 120 (90–160) mL; p<0.0001

Exploratory renal synthesis

13/680 vs 9/392

Different trial definitions; 22 events

RR 0.80 (95% CI 0.35–1.87); no equivalence inference

IVUS-ACS procedural exposure

Median contrast difference +13.1 mL

Procedural exposure rather than renal endpoint

Published 95% CI 9.5–16.9 mL

Evidence interpretation

Short-term creatinine-based events

Sparse events and different definitions

No established effect on dialysis or sustained renal decline

DOCTORS percentages are reproduced as published; the renal calculation uses the verified counts. RENOVATE nephropathy percentages are proportions rather than Kaplan–Meier estimates. Published definitions were retained.

DISCUSSION

This review examined whether intravascular imaging improves cardiovascular outcomes while preserving kidney safety in ACS. The compatible randomized estimates favoured imaging for TVF under conventional modelling. The result remained directionally favourable when a broader ACS composite was added. Renal evidence did not establish benefit. These findings support a qualified cardiovascular conclusion and a separate renal uncertainty statement. They do not justify presenting imaging as a proven method of preventing acute kidney injury in all ACS patients. The cardiovascular findings are relevant to Pakistan because the largest dedicated ACS trial included Pakistani centres. Their participation provides a stronger local connection than extrapolation from a wholly foreign trial. It still does not establish a Pakistan-specific effect or the performance of every local catheterisation laboratory. Access to equipment, device cost and operator experience may alter delivery of the intervention. Internationally, the favourable ACS findings sit alongside different results in mixed complex-PCI populations. This variation makes patient selection and achieved procedural quality more informative than a universal claim of benefit. The reduction in a vessel-oriented composite is clinically plausible. Cross-sectional imaging can identify an inadequate expansion result that remains difficult to appreciate from angiographic projections. Corrective dilation or additional treatment can then address a mechanical substrate for recurrent events. The intervention is therefore a sequence of measurement, interpretation and corrective action. Having an imaging catheter available does not ensure that this sequence is completed. This interpretation also explains why improvements in lumen dimensions and healing surrogates should not automatically be translated into survival benefit. High-risk clinical groups may obtain greater absolute benefit because their untreated event risk is higher. In the diabetes subgroup of IVUS-ACS, TVF was 3.6% versus 8.3% with HR 0.46 (95% CI 0.27–0.81). This supports consideration of imaging in patients with diabetes and ACS. It was not an additional independent trial and was excluded from the pooled denominator. Counting both the parent trial and this subgroup would exaggerate precision. The subgroup also cannot establish that diabetes alone determines which modality should be used. [26] A subsequent IVUS-ACS risk analysis found a more pronounced treatment effect in its higher-risk group. The TVF-ACS score combined clinical, laboratory and angiographic information rather than treating ACS as a uniform category. Its reported interaction requires validation before it becomes a stand-alone allocation rule. A prioritisation approach could be useful where imaging access is constrained but should preserve clinical judgement. High baseline risk may increase the value of optimisation while also increasing renal and bleeding vulnerability. Cardiovascular prioritisation should therefore be accompanied by a separate safety assessment. [27] Cost affects implementation in both Pakistan and other health systems. The RENOVATE economic analysis found higher short-term expenditure with imaging and more favourable results in lifetime modelling. These observations do not demonstrate immediate savings or affordability in Pakistani hospitals. Imported catheter prices, reimbursement and readmission costs can differ substantially. Local economic evaluation should examine both the initial procedure and downstream repeat treatment. A hospital should not assume that a lifetime model from Korea provides a local budget estimate. Training costs and equipment maintenance also belong in that assessment. [28] Representation and subgroup precision influence the apparent generalisability of the cardiovascular result. A RENOVATE analysis found no significant interaction between guidance strategy and sex. The smaller number of women still limits precision and should not be interpreted as proof of identical benefit in every female subgroup. Similarly, the high-bleeding-risk analysis found no significant treatment interaction by bleeding-risk category. These secondary analyses support cautious consistency but do not remove uncertainty from the small ACS-specific meta-analysis. They also do not allow an imaging benefit to replace individual antithrombotic decisions. [29,30] National renal observations show why kidney monitoring remains essential. A Pakistani prospective PCI study observed kidney injury in 15/159 patients (9.4%). That frequency was higher than the short-term rates in the randomized renal comparisons assembled here. The populations, creatinine definitions and study designs differed, so the difference cannot be attributed to imaging. It instead indicates that local baseline risk and ascertainment can change the observed event burden. Pakistani implementation should document baseline creatinine, contrast exposure and follow-up creatinine consistently rather than assuming that trial safety rates will transfer unchanged. [31] International nonrandomized evidence provides a possible renal mechanism but cannot resolve the randomized uncertainty. A Vietnamese prospective comparison reported lower contrast use and fewer kidney-injury events with IVUS. Assignment was not randomized. Operator selection and differences in patient or lesion risk could explain part of the association. Its favourable result was therefore excluded from the renal meta-analysis. The contrast with the randomized evidence illustrates why a clinically attractive renal hypothesis should remain separate from a causal conclusion. IVUS permits imaging without obligatory contrast flushing but its overall procedure may still use more angiographic contrast. [32] The CONSaVE-AKI randomized study evaluated an ultra-low-contrast strategy in high-risk ACS patients. Its intervention concerned contrast stewardship and selective imaging use rather than routine imaging assignment in every participant. It could not be substituted for an imaging-versus-angiography trial. The distinction is important in practice: reducing contrast requires a deliberate procedural plan. Renal risk assessment should consider haemodynamics and fluid tolerance as well as baseline filtration. Emergency reperfusion should remain timely. An imaging strategy and a contrast-saving strategy can complement each other but neither should be assumed from the presence of the other. [33] Renal vulnerability is also influenced by volume status. A prospective study of bioelectrical impedance assessment in stable coronary disease linked renal events to hydration-related measurements and clinical risk. Its stable population and observational design limit direct ACS extrapolation. It nonetheless supports investigating physiological factors beyond total contrast volume. In ACS, congestion may make indiscriminate fluid administration unsuitable. The current pooled renal interval includes clinically important benefit and harm. A nonsignificant p-value and low I² cannot establish renal equivalence when only 22 events are available. [34] Implementation priorities in low-resource settings should begin with reliable emergency pathways and evidence-based secondary prevention. A recent guideline-implementation statement emphasises adapting ACS care to local capacity. Imaging can be integrated within those pathways through explicit selection criteria, training and a documented optimisation checklist. Future trials should standardise renal definitions, collect creatinine at prespecified times and record dialysis and sustained loss of kidney function. They should recruit enough patients with chronic kidney disease to test renal safety directly. Contemporary cardiac and renal endpoints should be analysed without treating overlapping secondary reports as separate trials. [35] The principal limitations were the single-database search, access-dependent report assessment and absence of independent duplicate screening. Only two cohorts supplied compatible primary TVF hazard ratios. Additional trials had different endpoints or incompletely extractable ACS-specific results, creating availability bias. Follow-up differed and several cohorts were subgroups of mixed-population trials. Modified Hartung–Knapp intervals showed substantial small-study uncertainty. Renal definitions differed and events were sparse. Risk-of-bias appraisal was restricted by accessible reporting rather than a completed independent domain assessment. Publication bias could not be evaluated reliably. Predominantly Asian evidence and limited severe renal dysfunction representation restrict wider generalisability.

CONCLUSION

Intravascular imaging-guided PCI was associated with lower vessel-oriented cardiovascular event risk in the available randomized ACS evidence. The conventional pooled estimate favoured imaging but conservative sensitivity analysis showed substantial uncertainty from the small number of compatible cohorts.

 

 Short-term renal event data did not demonstrate kidney protection or establish equivalence. Imaging should support targeted procedural optimisation alongside deliberate contrast stewardship and renal monitoring. Larger ACS trials with standardised cardiovascular and kidney endpoints are needed to define benefit and safety across clinical risk groups.

 

Declarations

Financial support and sponsorship: Nil.

 

Conflicts of interest: There are no conflicts of interest.

 

Data availability: Published aggregate data and the reproducible extraction and calculation record underpin this analysis.

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