RESEARCH

BMJ: first published as 10.1136/bmj-2023-077848 on 16 November 2023. Downloaded from http://www.bmj.com/ on 1 December 2023 by guest. Protected by copyright.
Intravascular imaging guided versus coronary angiography
guided percutaneous coronary intervention: systematic review
and meta-analysis
Safi U Khan,1 Siddharth Agarwal,2 Hassaan B Arshad,1 Usman Ali Akbar,3 Mamas A Mamas,4,5
Shilpkumar Arora,6 Usman Baber,7 Sachin S Goel,1 Neal S Kleiman,1 Alpesh R Shah1
1
Department of Cardiology, Abstract intervention was associated with a reduced risk of
Houston Methodist DeBakey Objective cardiac death (rate ratio 0.53, 95% confidence interval
Heart and Vascular Center,
Houston, TX, USA
To assess the absolute treatment effects of 0.39 to 0.72), myocardial infarction (0.81, 0.68 to
2
Department of Medicine,
intravascular imaging guided versus angiography 0.97), stent thrombosis (0.44, 0.27 to 0.72), target
University of Oklahoma Health guided percutaneous coronary intervention in patients vessel revascularization (0.74, 0.61 to 0.89), and
Sciences Center, Oklahoma City, with coronary artery disease, considering their target lesion revascularization (0.71, 0.59 to 0.86) but
OK, USA baseline risk. not all cause death (0.81, 0.64 to 1.02). Using SYNTAX
3
Department of Medicine, risk categories, high certainty evidence showed that
West Virginia University - Design
Camden Clark Medical Center, Systematic review and meta-analysis. from low risk to high risk, intravascular imaging was
Parkersburg, WV, USA likely associated with 23 to 64 fewer cardiac deaths,
Data sources
4
Keele Cardiovascular Research 15 to 19 fewer myocardial infarctions, 9 to 13 fewer
Group, Keele University, Stroke- PubMed/Medline, Embase, and Cochrane Library
stent thrombosis events, 28 to 38 fewer target vessel
On-Trent, UK databases up to 31 August 2023.
5
revascularization events, and 35 to 48 fewer target
Department of Medicine, Study selection
Jefferson University, lesion revascularization events per 1000 people.
Philadelphia, PA, USA Randomized controlled trials comparing intravascular
Conclusions
6
University Hospitals Cleveland imaging (intravascular ultrasonography or optical
Compared with coronary angiography guided
Medical Center/Case Western coherence tomography) guided versus coronary
Reserve University, Cleveland,
percutaneous coronary intervention, intravascular
angiography guided percutaneous coronary
OH, USA imaging guided percutaneous coronary intervention
intervention in adults with coronary artery disease.
7
Department of Cardiology, was associated with significantly reduced cardiac
University of Oklahoma Health Main outcome measures death and cardiovascular outcomes in patients with
Sciences Center, Oklahoma City, Random effect meta-analysis and GRADE (grading of coronary artery disease. The estimated absolute
OK, USA recommendations, assessment, development, and effects of intravascular imaging guided percutaneous
Correspondence to: S U Khan evaluation) were used to assess certainty of evidence.
safinmc@gmail.com or coronary intervention showed a proportional
sukhan@houstonmethodist.org Data included rate ratios and absolute risks per 1000 relation with baseline risk, driven by the severity and
(or @safinmc on Twitter/X; people for cardiac death, myocardial infarction, stent complexity of coronary artery disease.
ORCID 0000-0003-1559-6911) thrombosis, target vessel revascularization, and target
Additional material is published Systematic review registration
lesion revascularization. Absolute risk differences
online only. To view please visit PROSPERO CRD42023433568.
the journal online. were estimated using SYNTAX risk categories for
Cite this as: BMJ 2023;383:e077848 baseline risks at five years, assuming constant rate Introduction
http://dx.doi.org/10.1136/ ratios across different cardiovascular risk thresholds.
bmj‑2023‑077848 The advent of drug eluting stents and advances
Results in intravascular imaging modalities, such as
Accepted: 10 October 2023 In 20 randomized controlled trials (n=11 698),
intravascular ultrasonography or optical coherence
intravascular imaging guided percutaneous coronary
tomography, have improved cardiovascular outcomes
in patients undergoing percutaneous coronary
intervention.1 Randomized controlled trials have
What is already known on this topic shown evidence supporting intravascular imaging
Randomized controlled trials have illustrated the potential benefits of guided percutaneous coronary intervention, primarily
intravascular imaging guided percutaneous coronary intervention (PCI) due to reduced rates of revascularization and stent
Notably, lower rates of target vessel failure and stent thrombosis have been thrombosis. For instance, the IVUS-XPL (Impact of
reported compared with angiography guided PCI Intravascular Ultrasound Guidance on the Outcomes
of Xience Prime Stents in Long Lesions) trial, involving
However, most trials were not adequately powered to evaluate individual
1400 participants, showed a sustained reduction in
cardiovascular endpoints, such as cardiac death or myocardial infarction
major adverse cardiovascular events over five years
What this study adds with intravascular ultrasonography in patients with
This meta-analysis of 20 randomized controlled trials showed that intravascular long lesions.2 However, most trials examining use of
imaging guided PCI was associated with reduced risk of cardiac death and intravascular ultrasonography in complex lesions were
cardiovascular outcomes relatively small and not sufficiently powered to assess
individual clinical endpoints.
These benefits were consistently observed across disease complexity, and
Two recent trials, OCTOBER (Optical Coherence
imaging modalities
Tomography Optimized Bifurcation Event Reduction)3
The greatest absolute benefits were observed in patients with the highest and ILUMIEN IV: OPTIMAL PCI (Optical Coherence
baseline risk, indicated by the severity and complexity of coronary artery disease Tomography Guided Coronary Stent Implantation

the bmj | BMJ 2023;383:e077848 | doi: 10.1136/bmj-2023-077848 1

 RESEARCH
Compared with Angiography: A Multicenter
Randomized Trial in Percutaneous Coronary
Intervention) 4 have shown conflicting results among
participants undergoing optical coherence tomography
guided versus angiography guided percutaneous
coronary intervention. Although OCTOBER showed
a reduction in cardiovascular outcomes with optical
coherence tomography guided percutaneous coronary
intervention at two years in complex coronary artery
bifurcation lesions, ILUMIEN IV: OPTIMAL PCI did
not show differences in outcomes between optical
coherence tomography and angiography guided
percutaneous coronary intervention at two years.
In this context, the absolute effects of intravascular
imaging seem likely to be influenced by an individual’s
baseline risk, primarily determined by the complexity
and severity of coronary artery disease.5 Furthermore,
concerns exist about the link between the increased
procedural time and potential exposure to radiation
associated with intravascular imaging guided
percutaneous coronary intervention. Therefore, we
did a meta-analysis of contemporary randomized
controlled trials to evaluate the absolute effects of
therapy considering the patient’s baseline risk and to
evaluate the balance between additional procedural
time and cardiovascular risk reduction in intravascular
imaging guided percutaneous coronary intervention.
Methods
We conducted this trial level meta-analysis according
to the Cochrane Collaboration guidelines and reported
5782
Records identified
2561 Embase 518 PubMed
2145 Medline 558 Cochrane
3456
Duplicates
2326
Records screened
2290
Excluded
1993 Irrelevant articles
268 Editorials or review articles
29 Systemic reviews and meta analyses
36
Full text articles assessed for eligibility
16
Excluded
9 Conference abstracts of included RCTs
7 Systemic reviews and meta analyses
20
Randomized controlled trials
included in quantitative synthesis
Fig 1 | Flowchart of study selection
2
BMJ: first published as 10.1136/bmj-2023-077848 on 16 November 2023. Downloaded from http://www.bmj.com/ on 1 December 2023 by guest. Protected by copyright.
it following the PRISMA (Preferred Reporting Items for
Systematic Reviews and Meta-Analysis).6 7
Data sources, searches, and study selection
We did a comprehensive literature search without
language restriction using PubMed/Medline, Embase,
and the Cochrane Library databases through 31
August 2023. We also searched websites of major
cardiovascular and medicine journals (www.nejm.org;
https://www.thelancet.com/; https://jamanetwork.
com; https://annals.org/aim; https://academic.
oup.com/eurheartj; www.onlinejacc.org; and www.
ahajournals.org/journal/circ) and bibliographies
of relevant studies.8-11 We used broad search terms
(“angiography”, “intravascular ultrasound”,
“IVUS”, “optical coherence tomography”, “OCT”,
“percutaneous coronary intervention”, and “PCI”)
(supplementary tables A-C).
The pre-specified inclusion criteria were randomized
controlled trials comparing intravascular imaging
(intravascular ultrasonography or optical coherence
tomography) guided versus coronary angiography
guided percutaneous coronary intervention in adults
with coronary artery disease, studies using drug eluting
stents, and studies reporting cardiovascular outcomes
of interest. We removed duplicates and screened the
remaining articles at the title and abstract level and
then at the full text level (fig 1). Two authors (SUK and
SA) independently conducted the study search and
selection process and resolved conflicts by discussion
and mutual consensus.
Data extraction
Two reviewers (SA and UAA) independently abstracted
the data into the data collection sheets, appraised the
accuracy of the data, did a risk of bias assessment,
and resolved discrepancies by discussion or referral
to the original publication. We abstracted data on
characteristics of trials (supplementary table D),
procedural and angiographic characteristics of patients
in the trials (supplementary table E), definition of
complex lesions used in trials (supplementary table F),
demographic and clinical characteristics of participants
(table 1), point estimates with 95% confidence intervals,
number of events, and sample sizes. We abstracted data
on the intention-to-treat principle.
Risk of bias in individual studies
We used a Cochrane risk of bias assessment tool for
assessing the risk of bias in randomized controlled
trials (supplementary figure A).29 We assessed the risk
of bias at the study level across the following domains:
bias due to the randomization process; bias due to
deviation from the intended intervention; bias due
to missing outcome data; bias in the measurement of
the outcomes; and bias in the selection of the reported
results, including divergence from the registered
protocol or owing to early termination for benefit. Two
reviewers (SA and UAA) independently appraised the
potential risks of bias, and discrepancies were resolved
by discussion or adjudication by a third party.
doi: 10.1136/bmj-2023-077848 | BMJ 2023;383:e077848 | the bmj
 Table 1 | Baseline demographics of trials and populations included in meta-analysis. Values are percentages unless stated otherwise
Median age, Previous Stable
Trial, year No of patients years Men Smoking HTN HLD Diabetes Previous MI Previous PCI CABG LVEF angina ACS
IVUS versus coronary angiography guided PCI
HOME DES IVUS, 105/105 59/60 73/71 40/35 67/71 63/66 42/45 37/32 17/14 14/10 NR 38/40 62/60
200912
RESET, 201313 269/274 63/64 66/55 22/17 61/66 61/62 32/30 1/3 - - 55/54 53/52 47/48
AVIO, 201314 142/142 64/64 82/77 35/31 70/67 70/77 24/27 - - - 55/56 70/64 30/26
Wang et al, 201415 38/42 56/54 60/67 50/59 39/24 26/24 21/12 - - - 50/48 0/0 100/100
MOZART, 201416 41/42 67/62 61/57 42/40 98/100 - 73/81 - 274/12 15/17 NR 76/71 15/17
AIR CTO, 201517 115/115 67/66 89/80 39/39 75/70 22/28 30/27 21/30 - - 55/56 71/76 29/24
CTO-IVUS, 201518 201/201 61/61 81/81 35/34 63/64 - 35/34 8/8 15/16 2/3 57/57 100/100 0/0

the bmj | BMJ 2023;383:e077848 | doi: 10.1136/bmj-2023-077848

IVUS-XPL, 20202 700/700 64/64 69/69 22/26 65/63 67/65 36/37 5/4 11/10 3/2 63/62 51/51 49/49
Tan et al, 201519 61/62 77/76 62/69 44/47 41/47 - 34/30 16/21 - - 55/53 30/34 70/66
Liu et al, 201920 167/169 65/65 64/64 37/36 70/72 38/38 34/31 17/14 20/17 1/1 56/58 12/11 86/87
ULTIMATE, 202121 724/724 65/66 74/73 35/32 71/72 54/55 30/31 9/12 17/20 1/1 61/60 13/13 79/78
OCT versus coronary angiography guided PCI
OCTACS, 201522 50/50 62/63 72/68 46/36 56/56 44/38 16/10 4/0 6/4 0/0 - 0/0 100/100
DOCTORS, 201623 120/120 61/60 79/76 42/41 42/49 47/48 16/19 - - - - 0/0 100/100
ROBUST, 201824 105/96 57/59 83/87 64/59 50/52 - 17/26 1/6 4/4 0/0 - 0/0 100/100
OPTIMUM, 202025 56/54 69/69 79/74 23/18 77/74 86/85 52/46 16/15 4/0 21/35 61/60 91/91 9/9
ILUMIEN IV: OPTIMIZE 1233/1254 65/66 78/76 19/20 71/74 66/69 42/42 20/24 13/13 63/53 55/55 27/29 63/61
PCI 20234
OCTOBER, 20233 600/601 66/66 69/69 50/51 70/75 76/78 17/16 28/30 41/43 1/2 59/58 55/53 45/47
IVUS/OCT versus coronary angiography guided PCI
iSIGHT, 202126 50/51/49 59/60/59 36/31/38 14/17/14 42/46/39 30/36/28 - - - - - 35/34/35 36/33/36
ILUMIEN III: OPTIMIZE 136/153/142 66/66/67 74/69/73 13/17/23 78/78/75 75/73/77 36/33/28 - - - - 35/34/35 36/33/36
PCI, 202127
RENOVATE-COMPLEX- 1092/547 65/66 79/79 19/17 62/59 51/51 36/41 7/8 24/23 - 58/59 49/50 51/50
PCI, 202328
ACS=acute coronary syndrome; AVIO=Angiography Versus IVUS Optimization; CABG=coronary artery bypass graft; CTO IVUS=Chronic Total Occlusion InterVention with drUg-eluting Stents guided by IVUS; DOCTORS=Does Optical Coherence Tomography
Optimize Results of Stenting; HLD=hyperlipidemia; HTN=hypertension; ILUMIEN IV=Optical Coherence Tomography (OCT) Guided Coronary Stent Implantation Compared with Angiography: A Multicenter Randomized Trial in PCI; iSIGHT=Optical Coherence
Tomography Versus Intravascular Ultrasound and Angiography to Guide Percutaneous Coronary Interventions; IVUS=intravascular ultrasonography; IVUS-XPL=Impact of Intravascular Ultrasound Guidance on the Outcomes of Xience Prime Stents in Long
Lesions; LVEF=left ventricular ejection fraction; MI=myocardial infarction; MOZART=Minimizing cOntrast utiliZation With IVUS Guidance in coRonary angioplasty; OCT=optical coherence tomography; OCTACS=Optical Coherence Tomography Guided
Percutaneous Coronary Intervention With Nobori Stent Implantation in Patients With Non-ST-Segment-Elevation Myocardial Infarction; OCTOBER=OCT or Angiography Guidance for PCI in Complex Bifurcation Lesions; OPTIMUM=Online 3-Dimensional
Optical Frequency Domain Imaging to Optimize Bifurcation Stenting Using UltiMaster Stent; PCI=percutaneous coronary intervention; RENOVATE COMPLEX-PCI=Randomized Controlled Trial of Intravascular Imaging Guidance versus Angiography-Guidance
on Clinical Outcomes after Complex Percutaneous Coronary Intervention; RESET=Real Safety and Efficacy of a 3-Month Dual Antiplatelet Therapy Following Zotarolimus-Eluting Stents Implantation; ULTIMATE=Intravascular Ultrasound Guided Drug Eluting
Stents Implantation in “All-Comers” Coronary Lesions.
RESEARCH

3
BMJ: first published as 10.1136/bmj-2023-077848 on 16 November 2023. Downloaded from http://www.bmj.com/ on 1 December 2023 by guest. Protected by copyright.
RESEARCH

Outcomes of interest
Our primary focus was cardiac death. Additional
endpoints included myocardial infarction, stent
thrombosis, target vessel revascularization, target
lesion revascularization, and all cause death. We also
evaluated differences in procedural characteristics—
that is, duration of procedure (minutes), fluoroscopy
time (minutes), and contrast volume (mL). We extracted
outcomes at the maximum follow-up duration.
Data synthesis and summary measures
We did a frequentist pairwise meta-analysis for all
patients and measured rate ratios for binary outcomes
and mean differences for continuous outcomes with
95% confidence intervals. We measured rate ratios per
person years to account for the difference in follow-
up duration as it assumes a constant risk over time.30
To calculate absolute risk differences, we applied the
pooled rate ratios from the meta-analysis to the baseline
risk. We used the baseline risk from the angiography
guided percutaneous coronary intervention arms of the
trials for all outcomes. To connect the two measures,
we used absolute risk difference = (rate ratio–1) ×
baseline risk per 1000 person years.
Baseline risk for clinical scenarios
To explore the applicability of the findings of our
meta-analysis to clinical practice, we did a series
of sensitivity analyses using data presented in the
SYNTAX (Synergy between Percutaneous coronary
intervention with Taxus and Cardiac Surgery) trials.5 31
Firstly, we determined the anticipated absolute effects
within distinct risk categories defined within the
SYNTAX trial. This trial delineated thirds of risk (mild
0-22, intermediate 23-32, and high ≥33) based on the
compilation of angiographic features. We then did
BMJ: first published as 10.1136/bmj-2023-077848 on 16 November 2023. Downloaded from http://www.bmj.com/ on 1 December 2023 by guest. Protected by copyright.
another sensitivity analysis using the SYNTAX-II trial
(supplementary table G), which used a scoring system
incorporating clinical and angiographic features.
We assumed that the pooled relative effects of
intravascular imaging guided versus coronary
angiographic guided percutaneous coronary
intervention are transportable across study
populations.32-35 We then took the event rates in the
percutaneous coronary intervention arm reported
for each SYNTAX risk category as baseline risks and
calculated anticipated absolute effects by multiplying
the pooled relative effects by the corresponding
baseline risks. We did a parallel analysis using data
from SYNTAX-II.31
Statistical analysis
We pooled outcomes by using a random effects model.
We applied the DerSimonian and Laird method to
estimate 𝜏.36 We used I2 statistics to measure the extent
of unexplained statistical heterogeneity: we considered
I2≥50% to be a high degree of between study statistical
heterogeneity.37 We assessed small study effects and
publication bias by using funnel plots and Egger’s
regression tests (supplementary figures B-G).
We did subgroup analyses according to age (<65 v
≥65 years), type of intravascular imaging (intravascular
ultrasonography versus optical coherence
tomography), setting (acute coronary syndrome versus
all comers), sample size (<500 v ≥500), and follow-
up duration (<1 v ≥1 year) (supplementary table H).
We did several sensitivity analyses: a leave-one-out
meta-analysis (supplementary table I); complex
coronary artery lesions (supplementary figures H-M);
absolute risk estimates using the SYNTAX score
categories (table 2); and absolute risk estimates
using the SYNTAX-II (supplementary table G). Finally,

Table 2 | Anticipated absolute risk differences (ARD) per 1000 people with 95% confidence intervals (CI) of intravascular imaging on outcomes in
patients undergoing percutaneous coronary intervention (PCI) across different coronary artery disease risk categories at five years
Baseline risk for coronary ARD (95% CI) with intravascular imaging
Risk categories Rate ratio (95% CI) angiography guided PCI guided PCI per 1000 people Certainty of evidence (GRADE)
Low risk (SYNTAX: 0-22)
Cardiac death 0.53 (0.39 to 0.72) 48 per 1000 23 (29 to 13) fewer High
Myocardial infarction 0.81 (0.68 to 0.97) 78 per 1000 15 (25 to 2) fewer High
Stent thrombosis 0.44 (0.27 to 0.72) 16 per 1000 9 (12 to 4) fewer High
Target vessel revascularization 0.74 (0.61 to 0.89) 108 per 1000 28 (42 to 12) fewer High
Target lesion revascularization 0.71 (0.59 to 0.86) 121 per 1000 35 (50 to 17) fewer High
All cause death 0.81 (0.64 to 1.02) 89 per 1000 17 fewer (32 fewer to 2 more) Moderate
Intermediate risk (SYNTAX: 22-32)
Cardiac death 0.53 (0.39 to 0.72) 88 per 1000 41 (54 to 25) fewer High
Myocardial infarction 0.81 (0.68 to 0.97) 112 per 1000 21 (36 to 3) fewer High
Stent thrombosis 0.44 (0.27 to 0.72) 19 per 1000 11 (14 to 5) fewer High
Target vessel revascularization 0.74 (0.61 to 0.89) 113 per 1000 29 (44 to 12) fewer High
Target lesion revascularization 0.71 (0.59 to 0.86) 128 per 1000 37 (52 to 18) fewer High
All cause death 0.81 (0.64 to 1.02) 138 per 1000 26 fewer (50 fewer to 3 more) Moderate
High risk (SYNTAX ≥33)
Cardiac death 0.53 (0.39 to 0.72) 136 per 1000 64 (83 to 38) fewer High
Myocardial infarction 0.81 (0.68 to 0.97) 101 per 1000 19 (32 to 3) fewer High
Stent thrombosis 0.44 (0.27 to 0.72) 23 per 1000 13 (17 to 6) fewer High
Target vessel revascularization 0.74 (0.61 to 0.89) 145 per 1000 38 (57 to 16) fewer High
Target lesion revascularization 0.71 (0.59 to 0.86) 164 per 1000 48 (67 to 23) fewer High
All cause death 0.81 (0.64 to 1.02) 192 per 1000 36 fewer (69 fewer to 4 more) Moderate
GRADE=grading of recommendations, assessment, development, and evaluation; SYNTAX=synergy between percutaneous coronary intervention with taxus and cardiac surgery.

4 doi: 10.1136/bmj-2023-077848 | BMJ 2023;383:e077848 | the bmj

 RESEARCH

we estimated the trade-off between procedural
characteristics and cardiovascular outcomes; that is,
to evaluate the procedural compromises associated
with intravascular imaging, we calculated the absolute
number of cardiovascular events increased or averted
for one additional procedural or fluoroscopy minute
when using intravascular imaging compared with a
coronary angiogram. The supplementary methods
report a detailed method for estimating absolute risk
differences.
For all analyses, we set statistical significance as
P<0.05. We used RevMan V 5.4 and MAGICapp (www.
magicapp.org) for all analyses.
Certainty of the evidence
Two authors (SUK and HBA) rated the certainty of
evidence as high, intermediate, low, or very low by
using the grading of recommendations assessment,
development, and evaluation (GRADE) approach
(https://gdt.gradepro.org/app/) (supplementary table J).
Patient and public involvement
No patients were involved in setting the research
question, outcome measures, study design, or data
interpretation. Besides lack of funding, the place
where this research took place was restricted and we
lacked the permission to engage patients. However,
after the production of our first manuscript draft, we
consulted a member of the public with established
cardiovascular disease who has been advised on
percutaneous coronary intervention for coronary
artery disease. We received feedback that the estimate
table (table 2) and certainty of evidence statements
were very useful, allowing assessment of the impact of
BMJ: first published as 10.1136/bmj-2023-077848 on 16 November 2023. Downloaded from http://www.bmj.com/ on 1 December 2023 by guest. Protected by copyright.
intravascular imaging guided percutaneous coronary
intervention with respect to absolute risk reduction
and certainty of risk reduction.
Results
Description of included trials
Of 5782 citations, we reviewed 2326 after removal of
duplicates. We excluded an additional 2306 studies on
the basis of the title and abstract level screening and
a priori selection criteria (fig 1). Finally, we included
20 trials (n=11 698) in the analysis (table 1). Eleven
trials (n=5139) exclusively focused on intravascular
ultrasonography, six trials (n=4339) used optical
coherence tomography, and three trials (n=2220) used
both types of imaging. Twelve trials (n=6113) were
conducted in patients with complex coronary lesions.
The median age of participants was 64 (interquartile
range 61-66) years. The median follow-up duration
was 1 (1-2) years.
Our risk of bias assessment showed that 10% (2/20)
of trials raised some concerns with the randomization
process, 5% (1/20) had deviations from the intended
intervention, 15% (3/20) had missing outcome
data, and 20% (4/20) had concerns about outcome
measurement. Funnel plots did not show small study
effects, and Egger’s regression test did not indicate the
presence of publication bias (P>0.05).
Differences in procedural characteristics
Eleven trials (n=8358) reported procedural time, five
trials (n=4560) reported fluoroscopy time, and 13 trials
(n=8789) reported contrast volume. Compared with
coronary angiography, intravascular imaging guided
percutaneous coronary intervention was associated

No of events/person years
Study or subgroup Intravascular Angiography Risk ratio, M-H, Weight Risk ratio, M-H,
imaging random (95% CI) (%) random (95% CI)

AIR CTO 2015 3/230 5/230 4.8 0.60 (0.15 to 2.48)

AVIO 2013 0/284 2/284 1.1 0.20 (0.01 to 4.15)
CTO-IVUS 2015 0/201 2/201 1.1 0.20 (0.01 to 1.14)
ILUMIEN IV 2023 9/2466 16/2508 14.6 0.57 (0.25 to 1.29)
iSIGHT 2021 1/252 1/122 1.3 0.48 (0.03 to 7.67)
IVUS-XPL 2020 6/3500 14/3500 10.6 0.43 (0.16 to 1.11)
Liu et al 2019 3/167 10/169 6.0 0.30 (0.09 to 1.08)
OCTACS 2015 0/50 1/50 1.0 0.33 (0.01 to 7.99)
OCTOBER 2023 8/1200 15/1202 13.3 0.53 (0.23 to 1.26)
RENOVATE-COMPLEX-PCI 2023 16/2184 17/1094 21.0 0.47 (0.24 to 0.93)
RESET 2013 0/269 1/274 0.9 0.34 (0.01 to 8.30)
Tan et al 2015 2/122 3/124 3.1 0.68 (0.12 to 3.98)
ULTIMATE 2021 15/2142 19/2127 21.3 0.78 (0.40 to 1.54)
Total 63/13 067 106/11 885 100.0 0.53 (0.39 to 0.72)
Test for heterogeneity: τ2=0.00; χ2=2.44, df=12, P=0.99; I2=0%
0.01 0.1 1 10 100
Test for overall effect: Z=4.01, P<0.001 Favors imaging Favors angiography

Fig 2 | Forest plot comparing intravascular imaging guided with coronary angiography guided percutaneous intervention for cardiac death. Data
obtained from randomized controlled trials using random effect meta-analysis and expressed as rate ratio. CI=confidence interval; M-H=Mantel-
Haenszel

the bmj | BMJ 2023;383:e077848 | doi: 10.1136/bmj-2023-077848 5

RESEARCH

BMJ: first published as 10.1136/bmj-2023-077848 on 16 November 2023. Downloaded from http://www.bmj.com/ on 1 December 2023 by guest. Protected by copyright.
No of events/person years
Study or subgroup Intravascular Angiography Risk ratio, M-H, Weight Risk ratio, M-H,
imaging random (95% CI) (%) random (95% CI)

AIR CTO 2015 20/230 15/230 7.7 1.33 (0.70 to 2.54)

AVIO 2013 10/284 12/284 4.7 0.83 (0.37 to 1.90)
CTO-IVUS 2015 0/201 2/201 0.3 0.20 (0.01 to 4.14)
DOCTORS 2016 1/60 1/60 0.4 1.00 (0.06 to 15.62)
HOME DES IVUS 2009 1/157 4/157 0.7 0.25 (0.03 to 2.21)
ILUMIEN IV 2023 57/2466 72/2508 27.0 0.81 (0.57 to 1.13)
iSIGHT 2021 5/252 6/122 2.3 0.40 (0.13 to 1.30)
IVUS-XPL 2020 4/3500 6/3500 2.0 0.67 (0.19 to 2.36)
Liu et al 2019 19/167 23/169 9.8 0.84 (0.47 to 1.48)
MOZART 2014 1/14 2/13 0.6 0.46 (0.05 to 4.53)
OCTOBER 2023 54/1200 54/1202 23.4 1.00 (0.69 to 1.45)
RENOVATE-COMPLEX-PCI 2023 43/2184 32/1094 15.6 0.67 (0.43 to 1.06)
RESET 2013 0/269 2/274 0.3 0.20 (0.01 to 4.22)
ROBUST 2018 1/79 0/72 0.3 2.74 (0.11 to 66.15)
Tan et al 2015 1/122 2/124 0.6 0.51 (0.05 to 5.53)
ULTIMATE 2021 7/2142 15/2127 4.0 0.46 (0.19 to 1.13)
Wang et al 2014 1/38 0/42 0.3 3.31 (0.14 to 78.84)
Total 225/13 365 248/12 179 100.0 0.81 (0.68 to 0.97)
Test for heterogeneity: τ2=0.00; χ2=11.65, df=16, P=0.77; I2=0%
0.01 0.1 1 10 100
Test for overall effect: Z=2.26, P=0.02 Favors imaging Favors angiography

Fig 3 | Forest plot comparing intravascular imaging guided with coronary angiography guided percutaneous intervention for myocardial infarction
(bottom). Data obtained from randomized controlled trials using random effect meta-analysis and expressed as rate ratio. CI=confidence interval;
M-H=Mantel-Haenszel

with increased procedural time (mean difference
15.68 (95% confidence interval 13.29 to 18.07) min;
P≤0.01; I2=69%), fluoroscopy time (3.23 (2.25 to
4.21) min; P≤0.01; I2=78%), and contrast volume
use (26.46 (11.14 to 41.78) mL; P≤0.01; I2=95%).
Optical coherence tomography was associated with
higher usage of contrast volume (mean difference
54.19 (31.43 to 76.95) mL; P<0.01; I2=96%) than
intravascular ultrasonography (0.21 (−23.54 to 23.96)
mL; P=0.99; I2=87%) (P for interaction <0.01).

No of events/person years
Study or subgroup Intravascular Angiography Risk ratio, M-H, Weight Risk ratio, M-H,
imaging random (95% CI) (%) random (95% CI)

AIR CTO 2015 1/230 7/230 5.5 0.14 (0.02 to 1.15)

CTO-IVUS 2015 0/201 3/201 2.7 0.14 (0.01 to 2.75)
HOME DES IVUS 2009 4/157 6/157 15.3 0.67 (0.19 to 2.32)
ILUMIEN III 2021 1/289 0/142 2.3 1.48 (0.06 to 36.09)
ILUMIEN IV 2023 6/2466 17/2508 27.5 0.36 (0.14 to 0.91)
IVUS-XPL 2020 2/3500 2/3500 6.2 1.00 (0.14 to 7.10)
Liu et al 2019 2/167 5/169 9.0 0.40 (0.08 to 2.06)
OCTACS 2015 0/50 1/50 2.4 0.33 (0.01 to 7.99)
OCTOBER 2023 5/1200 5/1202 15.5 1.00 (0.29 to 3.45)
RENOVATE-COMPLEX-PCI 2023 1/2184 4/1094 5.0 0.13 (0.01 to 1.12)
RESET 2013 1/269 1/274 3.1 1.02 (0.06 to 16.20)
ULTIMATE 2021 1/2142 8/2127 5.5 0.12 (0.02 to 0.99)
Total 24/12 855 59/11 654 100.0 0.44 (0.27 to 0.72)
Test for heterogeneity: τ2=0.00; χ2=8.45, df=11, P=0.67; I2=0%
0.01 0.1 1 10 100
Test for overall effect: Z=3.29, P=0.001 Favors imaging Favors angiography

Fig 4 | Forest plot comparing intravascular imaging guided with coronary angiography guided percutaneous intervention for stent thrombosis. Data
obtained from randomized controlled trials using random effect meta-analysis and expressed as rate ratio. CI=confidence interval; M-H=Mantel-
Haenszel

6 doi: 10.1136/bmj-2023-077848 | BMJ 2023;383:e077848 | the bmj

 RESEARCH

BMJ: first published as 10.1136/bmj-2023-077848 on 16 November 2023. Downloaded from http://www.bmj.com/ on 1 December 2023 by guest. Protected by copyright.
No of events/person years
Study or subgroup Intravascular Angiography Risk ratio, M-H, Weight Risk ratio, M-H,
imaging random (95% CI) (%) random (95% CI)

AIR CTO 2015 9/230 14/230 5.5 0.64 (0.28 to 1.46)

AVIO 2013 1/284 5/284 0.8 0.20 (0.02 to 1.70)
CTO-IVUS 2015 5/201 10/201 3.3 0.50 (0.17 to 1.44)
DOCTORS 2016 2/60 1/60 0.6 2.00 (0.19 to 21.47)
ILUMIEN III 2021 7/289 2/142 1.5 1.72 (0.36 to 8.17)
ILUMIEN IV 2023 66/2466 67/2508 32.4 1.00 (0.72 to 1.40)
Liu et al 2019 7/167 15/169 4.8 0.47 (0.20 to 1.13)
OCTOBER 2023 19/1200 29/1202 11.1 0.66 (0.37 to 1.16)
RENOVATE-COMPLEX-PCI 2023 32/2184 25/1094 13.6 0.64 (0.38 to 1.08)
RESET 2013 12/269 18/274 7.2 0.68 (0.33 to 1.38)
ULTIMATE 2021 32/2142 49/2127 18.7 0.65 (0.42 to 1.01)
Wang et al 2014 0/38 2/42 0.4 0.22 (0.01 to 4.45)
Total 192/9530 237/8333 100.0 0.74 (0.61 to 0.89)
Test for heterogeneity: τ2=0.00; χ2=9.52, df=11, P=0.57; I2=0%
0.01 0.1 1 10 100
Test for overall effect: Z=3.13, P=0.002 Favors imaging Favors angiography

Fig 5 | Forest plot comparing intravascular imaging guided with coronary angiography guided percutaneous intervention for target vessel
revascularization. Data obtained from randomized controlled trials using a random effect meta-analysis and expressed as rate ratio. CI=confidence
interval; M-H=Mantel-Haenszel

Cardiac death Myocardial infarction and stent thrombosis

Thirteen trials (n=10 007) reported cardiac death.
Compared with coronary angiography, intravascular
imaging was associated with reduced risk of cardiac
death (rate ratio 0.53, 95% confidence interval 0.39 to
0.72; P<0.001; I2=0%; fig 2) (absolute risk difference
10 (95% confidence interval 13 to 6) fewer per 1000
person years; high certainty).
A total of 17 trials (n=11 057) reported myocardial
infarction, and 12 trials (n=10 327) reported stent
thrombosis. Compared with coronary angiography,
intravascular imaging was associated with reduced
risk of myocardial infarction (rate ratio 0.81, 0.68 to
0.97; P=0.02; I2=0%; fig 3) (absolute risk difference 9
(15 to 1) fewer per 1000 person years; high certainty)

No of events/person years
Study or subgroup Intravascular Angiography Risk ratio, M-H, Weight Risk ratio, M-H,
imaging random (95% CI) (%) random (95% CI)

AIR CTO 2015 8/230 12/230 3.4 0.67 (0.28 to 1.60)

AVIO 2013 13/284 17/284 6.9 0.76 (0.38 to 1.54)
CTO-IVUS 2015 5/201 8/201 2.8 0.63 (0.21 to 1.88)
HOME DES IVUS 2009 6/157 6/157 2.8 1.00 (0.33 to 3.03)
ILUMIEN III 2021 6/289 2/142 1.4 1.47 (0.30 to 7.21)
ILUMIEN IV 2023 53/2466 51/2508 23.5 1.06 (0.72 to 1.55)
iSIGHT 2021 1/252 0/122 0.3 1.46 (0.06 to 35.54)
IVUS-XPL 2020 31/3500 55/3500 17.8 0.56 (0.36 to 0.87)
Liu et al 2019 2/167 5/169 1.3 0.40 (0.08 to 2.06)
OCTOBER 2023 18/1200 28/1202 9.9 0.64 (0.36 to 1.16)
RENOVATE-COMPLEX-PCI 2023 24/2184 20/1094 9.8 0.60 (0.33 to 1.08)
ROBUST 2018 2/79 1/72 0.6 1.82 (0.17 to 19.68)
Tan et al 2015 5/122 12/124 3.3 0.42 (0.15 to 1.17)
ULTIMATE 2021 27/2142 45/2127 15.2 0.60 (0.37 to 0.96)
Total 201/13 273 262/11 932 100.0 0.71 (0.59 to 0.86)
Test for heterogeneity: τ2=0.00; χ2=9.76, df=13, P=0.71; I2=0%
0.01 0.1 1 10 100
Test for overall effect: Z=3.62, P<0.001 Favors imaging Favors angiography

Fig 6 | Forest plot comparing intravascular imaging guided with coronary angiography guided percutaneous coronary intervention for target lesion
revascularization. Data obtained from randomized controlled trials using random effect meta-analysis and expressed as risk ratio. CI=confidence
interval; M-H=Mantel-Haenszel

the bmj | BMJ 2023;383:e077848 | doi: 10.1136/bmj-2023-077848 7

RESEARCH

and stent thrombosis (rate ratio 0.44, 0.27 to 0.72;
P=0.001; I2=0%; fig 4) (absolute risk difference 7 (9 to
3) fewer per 1000 person years; high certainty).
Target vessel revascularization, target lesion
revascularization, and all cause death
Twelve trials (n=9321) reported target vessel
revascularization, 14 trials (n=10 542) reported target
lesion revascularization, and 13 trials (n=9174)
reported all cause deaths. Compared with coronary
angiography, intravascular imaging was associated
with a reduced risk of target vessel revascularization
(rate ratio 0.74, 0.61 to 0.89; P=0.002; I2=0%; fig
5) (absolute risk difference 14 (21 to 6) fewer per
1000 person years; high certainty) and target lesion
revascularization (rate ratio 0.71, 0.59 to 0.86;
P<0.001; I2=0%; fig 6) (absolute risk difference 18
(25 to 9) fewer per 1000 person years; high certainty).
However, intravascular imaging was not associated
with a significant reduction in all cause deaths (rate
ratio 0.81, 0.64 to 1.02; P=0.07; I2=0%; fig 7) (absolute
risk difference 4 (8 to 0) fewer per 1000 person years;
moderate certainty).
Trade-off between procedural time and
cardiovascular outcomes
When assessing the trade-off between the additional
procedural time (~15 min) and fluoroscopy time
(~3 min) and its effect on cardiovascular outcomes,
we calculated that for each additional procedural
minute spent using intravascular imaging we could
anticipate averting approximately 1 (95% confidence
interval 1 to 0) cardiac death, 1 (1 to 0) myocardial
infarction, 1 (1 to 0) target vessel revascularization
event, and 1 (2 to 1) target lesion revascularization
BMJ: first published as 10.1136/bmj-2023-077848 on 16 November 2023. Downloaded from http://www.bmj.com/ on 1 December 2023 by guest. Protected by copyright.
event per 1000 people with use of intravascular
imaging guided percutaneous coronary intervention.
Furthermore, each additional minute of fluoroscopy
with intravascular imaging could potentially prevent
around 3 (4 to 2) cardiac deaths, 3 (5 to 0) myocardial
infarctions, 2 (3 to 1) stent thrombosis events, 5 (7 to
2) target vessel revascularization events, and 6 (8 to 3)
target lesion revascularization events per 1000 people.
Sensitivity analysis
Summary results were largely consistent in trials of
complex coronary artery lesions (supplementary
figures H-M). On the basis of the SYNTAX risk
stratification, high certainty evidence showed that
for low to high risk patients, intravascular imaging
was likely associated with 23 (29 to 13) fewer to 64
(83 to 38) fewer cardiac deaths, 15 (25 to 2) fewer to
19 (32 to 3) fewer myocardial infarctions, 9 (12 to 4)
fewer to 13 (17 to 6) fewer stent thrombosis events,
28 (42 to 12) fewer to 38 (57 to 16) fewer target vessel
revascularization events, and 35 (50 to 17) fewer to 48
(67 to 23) fewer target lesion revascularization events
1000 people (table 2).
Using the SYNTAX-II score, high certainty evidence
showed that intravascular imaging could lead to 13
fewer (17 fewer to 8 fewer) cardiac deaths, 5 fewer (9
fewer to 1 fewer) myocardial infarctions, 8 fewer (10
fewer to 4 fewer) stent thrombosis events, 16 fewer
(23 fewer to 7 fewer) target vessel revascularization
events, and16 fewer (23 fewer to 8 fewer) target lesion
revascularization events per 1000 people.
Subgroup analyses
Statistical analysis showed no significant interaction
effects for various subgroups (including age, type of

No of events/person years
Study or subgroup Intravascular Angiography Risk ratio, M-H, Weight Risk ratio, M-H,
imaging random (95% CI) (%) random (95% CI)

AIR CTO 2015 6/230 7/230 4.7 0.86 (0.29 to 2.51)

CTO-IVUS 2015 2/201 3/201 1.7 0.67 (0.11 to 3.95)
DOCTORS 2016 1/60 0/60 0.5 3.00 (0.12 to 72.20)
HOME DES IVUS 2009 3/157 2/157 1.7 1.50 (0.25 to 8.85)
ILUMIEN III 2021 7/289 3/142 3.0 1.15 (0.30 to 4.37)
ILUMIEN IV 2023 32/2466 44/2508 26.4 0.74 (0.47 to 1.16)
iSIGHT 2021 2/252 1/122 0.9 0.97 (0.09 to 10.57)
MOZART 2014 0/14 2/13 0.6 0.19 (0.01 to 3.56)
OCTOBER 2023 13/1200 23/1202 11.8 0.57 (0.29 to 1.11)
OPTIMUM 2020 1/55 0/50 0.5 2.73 (0.11 to 65.57)
RENOVATE-COMPLEX-PCI 2023 42/2184 28/1094 24.2 0.75 (0.47 to 1.21)
RESET 2013 3/269 2/274 1.7 1.53 (0.26 to 9.07)
ULTIMATE 2021 31/2142 31/2127 22.1 0.99 (0.61 to 1.63)
Total 143/9519 146/8180 100.0 0.81 (0.64 to 1.02)
Test for heterogeneity: τ2=0.00; χ2=5.44, df=12, P=0.94; I2=0%
0.01 0.1 1 10 100
Test for overall effect: Z=1.80, P=0.07 Favors imaging Favors angiography

Fig 7 | Forest plot comparing intravascular imaging guided with coronary angiography guided percutaneous coronary intervention for all cause
death. Data obtained from randomized controlled trials using random effect meta-analysis and expressed as risk ratio. CI=confidence interval;
M-H=Mantel-Haenszel

8 doi: 10.1136/bmj-2023-077848 | BMJ 2023;383:e077848 | the bmj


intravascular imaging used, stent generation, setting,
sample size, and follow-up duration), indicating that
the relative effects of the intravascular imaging were
consistent across these subgroups (supplementary
table H).
Discussion
In this meta-analysis of 11 698 patients undergoing
percutaneous coronary intervention with drug
eluting stents, high certainty evidence suggested that
intravascular imaging guided percutaneous coronary
intervention was associated with reduced risk of cardiac
death and cardiovascular outcomes compared with
coronary angiography guided percutaneous coronary
intervention. Although the duration of procedural
and fluoroscopy time was extended by intravascular
imaging guided percutaneous coronary intervention,
the benefits of this approach outweighed the potential
risks. Finally, the estimated absolute benefits of
intravascular imaging guided percutaneous coronary
intervention showed a proportional relation with
baseline risk, driven by the severity and complexity of
coronary artery disease.
Strengths and limitations of study
We focused on the absolute effects of intravascular
imaging by adopting a risk based approach and
evaluating the certainty of evidence with the GRADE
framework, which assists clinicians in devising tailored
treatment strategies rather than merely concentrating
on the relative effects of the intervention. In addition,
we observed a decrease in myocardial infarction,
revascularization rates, and stent thrombosis
accompanied by increased life expectancy due to
cardiac causes. This observation becomes crucial when
we consider the results from the RENOVATE-COMPLEX
PCI (Guidance vs. Angiography-Guidance on Clinical
Outcomes after Complex Percutaneous Coronary
Intervention) trial.28 In that trial, intravascular
imaging guided percutaneous coronary intervention
was associated with reduced cardiac deaths compared
with coronary angiography guided percutaneous
coronary intervention.28 However, the secondary
endpoints were not adjusted for multiple comparisons.
Furthermore, specific outcomes such as myocardial
infarction, revascularization, and stent thrombosis
did not show significant reductions with intravascular
imaging guided percutaneous coronary intervention,
complicating the interpretation of the noted cardiac
survival advantage with this method.28
Increased procedural time, contrast dose, and
radiation exposure have been linked to periprocedural
complications such as early mortality, emergency
coronary artery bypass grafting, cancer, and contrast
induced nephropathy.38 Concerns exist about the
additional procedural time and potential higher
radiation exposure associated with intravascular
imaging.39 Although our study could not assess
the direct association between radiation dose and
outcomes, fluoroscopy time can be considered a
convenient proxy for radiation exposure. Our findings
the bmj | BMJ 2023;383:e077848 | doi: 10.1136/bmj-2023-077848
RESEARCH
BMJ: first published as 10.1136/bmj-2023-077848 on 16 November 2023. Downloaded from http://www.bmj.com/ on 1 December 2023 by guest. Protected by copyright.
indicate that the protective effect against cardiovascular
events outweighs the additional fluoroscopy time or
procedural duration.
Nevertheless, this meta-analysis has limitations.
Firstly, the included trials have varied participant
populations, outcome definitions, and follow-up
periods. Secondly, we did pre-planned overall and
subgroup analyses at a study level rather than an
individual patient level. Therefore, we could not assess
certain crucial aspects, such as the influence of stent
sizing before or after intravascular imaging guided
percutaneous coronary intervention, on cardiovascular
outcomes. Thirdly, the criteria used for intravascular
imaging guidance varied across trials. Fourthly, we
did an evaluation of the five year baseline risk for
various SYNTAX strata, which may potentially result
in an overestimation of baseline risk. This is because
the original SYNTAX study used first generation stents
without incorporating contemporary antiplatelet
regimens. To overcome this concern, we have also
provided estimates based on the SYNTAX-II score. This
allows clinicians the flexibility to choose either scoring
system to estimate potential absolute risk reductions.
Fifthly, we assumed similar relative risk reductions
with intravascular imaging in the different SYNTAX
categories, which may not necessarily be the case.
Finally, while focusing on analyzing angiographic
lesions through the SYNTAX scoring system, healthcare
professionals must not forget to use their clinical
expertise when drawing conclusions from our findings.
Comparisons with other studies
Although many meta-analyses have studied
intravascular imaging guided percutaneous coronary
intervention, a systematic review of 24 meta-analyses
showed that only nine focused exclusively on
randomized controlled trials.40 Given the potential
for observational studies to introduce confounding,41
we focused exclusively on evidence obtained from
randomized controlled trials. In addition, we chose
cardiac death as our primary endpoint for analysis,
which is more specific than the heterogeneous major
adverse cardiovascular events endpoint used in
previous meta-analyses. Cardiac death provides a
more focused measure than all cause death, which
is more likely to be influenced by competing risks,
potentially diluting the effect of the intervention.
Finally, to our knowledge, no previous meta-analyses
have investigated the balance between extended
procedural time, longer fluoroscopy duration,
increased contrast volume, and the potential benefits
of intravascular imaging guided percutaneous
coronary intervention.8-10
Clinical uncertainties
Although the point estimate and the upper bound of
the confidence interval hinted at a possible reduction
in all cause death with intravascular imaging guided
percutaneous coronary intervention, this did not reach
statistical significance. The wide confidence intervals
for all cause death reflect low event rates. Additionally,
9
RESEARCH
with a median follow-up duration of just one year for
this study, detecting a statistically significant difference
between the two interventions would require more
extended follow-up periods and higher event rates.
Policy implications
The implications of this meta-analysis for clinical
guidelines and the adoption of imaging guided
strategies are multifaceted. The American College of
Cardiology, American Heart Association, and Society
for Cardiovascular Angiography and Interventions
guidelines for coronary revascularization recommend
intravascular ultrasonography for procedural
guidance, particularly in cases involving left
main or complex coronary artery disease (class of
recommendation: 2a).1 Similarly, the European Society
of Cardiology and European Association for Cardio-
Thoracic Surgery guidelines suggest intravascular
ultrasonography or optical coherence tomography
for selected patients to optimize stent implantation
and intravascular ultrasonography for unprotected
left main lesions (class IIa).42 Additionally, the recent
European Association of Percutaneous Cardiovascular
Interventions consensus statement also recommends
the use of imaging guided percutaneous coronary
intervention only in select groups of patients with
complex lesions (including long lesions, chronic
total occlusions, or left main lesions) and patients
presenting with acute coronary syndrome, citing less
benefit in non-complex lesions or patients with more
stable clinical presentation.43 Given the observed
benefits of intravascular imaging guided percutaneous
coronary intervention, reassessing current guidelines
and considering revisions to better reflect the evidence
presented in this study are imperative.44
Despite its established benefits, the use of
intravascular imaging to optimize percutaneous
coronary intervention remains low in the US. A
nationwide US study showed that use of intravascular
imaging was below 5% between 2004 and 2014.45
A large state registry in Michigan showed that only
5.6% of all percutaneous coronary interventions
in Medicare patients were done with intravascular
ultrasonography.46 The results of this meta-analysis
should encourage wider adoption of intravascular
imaging guided percutaneous coronary intervention
in clinical practice. A more systematic application of
intravascular imaging as a complement to angiography
would be advisable, especially for left main or proximal
left anterior descending lesions, in-stent restenosis,
stent thrombosis, chronic total occlusions, calcified
coronary arteries, or any other situation in which
angiography does not adequately show the coronary
anatomy. Finally, as intravascular imaging guided
percutaneous coronary intervention becomes more
widespread, evaluating its cost effectiveness is crucial.
A health economic assessment showed that considering
5% annual discounting, intravascular ultrasonography
correlated with an increased lifetime expense of $597
per person.47 This additional cost, however, was offset
by a gain of 0.04 life years and 0.05 quality adjusted
10
BMJ: first published as 10.1136/bmj-2023-077848 on 16 November 2023. Downloaded from http://www.bmj.com/ on 1 December 2023 by guest. Protected by copyright.
life years compared with angiography, resulting in
an incremental cost effectiveness ratio of $12 730 per
quality adjusted life year.47 Additionally, exploratory
analyses suggested that intravascular ultrasonography
had greater cost effectiveness among patients with
left main and complex coronary lesions, indicating
its potential for both improved health outcomes and
efficient resource use in these subgroups.47
Conclusion
This meta-analysis showed that intravascular imaging
guided percutaneous coronary intervention was
associated with reduced risk of cardiac death, driven
by cardiovascular outcomes for patients undergoing
percutaneous coronary intervention with drug eluting
stents. The results were consistent across different
imaging types and patient populations. The most
significant benefits of intravascular imaging guided
percutaneous coronary intervention were observed in
patients with the most severe and complex coronary
artery disease. Finally, the additional time invested in
the procedure is outweighed by the positive outcomes
and advantages associated with this approach.
Contributors: SUK and SA are joint first authors. SUK conceived the
study. SUK and SA designed search strategy, did the literature search,
and screened studies for eligibility. SUK and UAA assessed the risk
of bias and extracted data. SUK and HBA evaluated the certainty
of evidence. SUK, SA, HBA, UAA, MAM, SA, UB, SSG, NSK, and ARS
interpreted the data analysis. SUK wrote the first draft of the manuscript,
and all other authors revised it. SUK and SA are the guarantors. The
corresponding author attests that all listed authors meet authorship
criteria and that no others meeting the criteria have been omitted.
Funding: This review did not receive any funding.
Competing interests: All authors have completed the ICMJE uniform
disclosure form at https://www.icmje.org/disclosure-of-interest/ and
declare: no support from any organization for the submitted work;
NSK has received grants or contracts from Boston Scientific for work
as a clinical trial investigator; SSG has received consulting fees from
Medtronic, JC Medical, and WL Gore Associates and honorariums from
Abbott Structural Heart; MAM has received institutional grants from
Abbott Vascular and Terumo and honorariums from Terumo, Amgen,
and Abbott Vascular Biosensors; UB has received honorariums from
Boston Scientific and Abbott; no other relationships or activities that
could appear to have influenced the submitted work.
Ethical approval: Not required.
Data sharing: The statistical code and dataset are available from the
corresponding author.
The lead authors (the manuscript’s guarantors) affirm that the
manuscript is an honest, accurate and transparent account of the
study being reported; that no important aspects of the study have
been omitted; and that any discrepancies from the study as planned
and registered have been explained
Dissemination to participants and related patient and public
communities: We intend to engage the public in disseminating
our results, including social media engagement, newsletters, and
conferences.
Provenance and peer review: Not commissioned; externally peer
reviewed.
This is an Open Access article distributed in accordance with the
Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license,
which permits others to distribute, remix, adapt, build upon this work
non-commercially, and license their derivative works on different
terms, provided the original work is properly cited and the use is non-
commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
1 Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/
SCAI Guideline for Coronary Artery Revascularization: Executive
Summary: A Report of the American College of Cardiology/
American Heart Association Joint Committee on Clinical Practice
Guidelines. Circulation 2022;145:e4-17. doi:10.1161/
CIR.0000000000001039
doi: 10.1136/bmj-2023-077848 | BMJ 2023;383:e077848 | the bmj

2 Hong SJ, Mintz GS, Ahn CM, et al, IVUS-XPL Investigators. Effect of
Intravascular Ultrasound-Guided Drug-Eluting Stent Implantation:
5-Year Follow-Up of the IVUS-XPL Randomized Trial. JACC Cardiovasc
Interv 2020;13:62-71. doi:10.1016/j.jcin.2019.09.033
3 Holm NR, Andreasen LN, Neghabat O, et al, OCTOBER Trial Group.
OCT or Angiography Guidance for PCI in Complex Bifurcation Lesions.
N Engl J Med 2023;389:1477-87. doi:10.1056/NEJMoa2307770
4 Ali ZA, Landmesser U, Maehara A, et al, ILUMIEN IV Investigators.
Optical Coherence Tomography-Guided versus Angiography-
Guided PCI. N Engl J Med 2023;389:1466-76. doi:10.1056/
NEJMoa2305861
5 Mohr FW, Morice MC, Kappetein AP, et al. Coronary artery bypass graft
surgery versus percutaneous coronary intervention in patients with
three-vessel disease and left main coronary disease: 5-year follow-up
of the randomised, clinical SYNTAX trial. Lancet 2013;381:629-38.
doi:10.1016/S0140-6736(13)60141-5
6 van Tulder M, Furlan A, Bombardier C, Bouter L, Editorial Board of
the Cochrane Collaboration Back Review Group. Updated method
guidelines for systematic reviews in the cochrane collaboration
back review group. Spine (Phila Pa 1976) 2003;28:1290-9.
doi:10.1097/01.BRS.0000065484.95996.AF
7 Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred
reporting items for systematic reviews and meta-analyses: the
PRISMA statement. PLoS Med 2009;6:e1000097. doi:10.1371/
journal.pmed.1000097
8 Buccheri S, Franchina G, Romano S, et al. Clinical Outcomes
Following Intravascular Imaging-Guided Versus Coronary
Angiography-Guided Percutaneous Coronary Intervention With Stent
Implantation: A Systematic Review and Bayesian Network Meta-
Analysis of 31 Studies and 17,882 Patients. JACC Cardiovasc
Interv 2017;10:2488-98. doi:10.1016/j.jcin.2017.08.051
9 Ahn JM, Kang S-J, Yoon SH, et al. Meta-analysis of outcomes after
intravascular ultrasound-guided versus angiography-guided
drug-eluting stent implantation in 26,503 patients enrolled
in three randomized trials and 14 observational studies. Am J
Cardiol 2014;113:1338-47. doi:10.1016/j.amjcard.2013.12.043
10 Darmoch F, Alraies MC, Al-Khadra Y, Moussa Pacha H, Pinto
DS, Osborn EA. Intravascular Ultrasound Imaging-Guided
Versus Coronary Angiography-Guided Percutaneous Coronary
Intervention: A Systematic Review and Meta-Analysis. J Am Heart
Assoc 2020;9:e013678. doi:10.1161/JAHA.119.013678
11 Niu Y, Bai N, Ma Y, Zhong PY, Shang YS, Wang ZL. Efficacy of
intravascular imaging-guided drug-eluting stent implantation: a
systematic review and meta-analysis of randomized clinical trials.
BMC Cardiovasc Disord 2022;22:327. doi:10.1186/s12872-022-
02772-w
12 Jakabčin J, Špaček R, Bystroň M, et al. Long-term health outcome and
mortality evaluation after invasive coronary treatment using drug
eluting stents with or without the IVUS guidance. Randomized control
trial. HOME DES IVUS. Catheter Cardiovasc Interv 2010;75:578-83.
doi:10.1002/ccd.22244
13 Kim J-S, Kang T-S, Mintz GS, et al. Randomized comparison of clinical
outcomes between intravascular ultrasound and angiography-
guided drug-eluting stent implantation for long coronary artery
stenoses. JACC Cardiovasc Interv 2013;6:369-76. doi:10.1016/j.
jcin.2012.11.009
14 Chieffo A, Latib A, Caussin C, et al. A prospective, randomized trial of
intravascular-ultrasound guided compared to angiography guided
stent implantation in complex coronary lesions: the AVIO trial. Am
Heart J 2013;165:65-72. doi:10.1016/j.ahj.2012.09.017
15 Wang H-X, Dong P-S, Li Z-J, Wang HL, Wang K, Liu XY. Application of
Intravascular Ultrasound in the Emergency Diagnosis and Treatment
of Patients with ST-Segment Elevation Myocardial Infarction.
Echocardiography 2015;32:1003-8. doi:10.1111/echo.12794
16 Mariani JJr, Guedes C, Soares P, et al. Intravascular ultrasound
guidance to minimize the use of iodine contrast in percutaneous
coronary intervention: the MOZART (Minimizing cOntrast utiliZation
With IVUS Guidance in coRonary angioplasTy) randomized controlled
trial. JACC Cardiovasc Interv 2014;7:1287-93. doi:10.1016/j.
jcin.2014.05.024
17 Tian N-L, Gami S-K, Ye F, et al. Angiographic and clinical comparisons
of intravascular ultrasound- versus angiography-guided drug-
eluting stent implantation for patients with chronic total occlusion
lesions: two-year results from a randomised AIR-CTO study.
EuroIntervention 2015;10:1409-17. doi:10.4244/EIJV10I12A245
18 Kim BK, Shin DH, Hong MK, et al, CTO-IVUS Study Investigators.
Clinical Impact of Intravascular Ultrasound-Guided Chronic
Total Occlusion Intervention With Zotarolimus-Eluting Versus
Biolimus-Eluting Stent Implantation: Randomized Study.
Circ Cardiovasc Interv 2015;8:e002592. doi:10.1161/
CIRCINTERVENTIONS.115.002592
19 Tan Q, Wang Q, Liu D, Zhang S, Zhang Y, Li Y. Intravascular
ultrasound-guided unprotected left main coronary artery stenting
in the elderly. Saudi Med J 2015;36:549-53. doi:10.15537/
smj.2015.5.11251
the bmj | BMJ 2023;383:e077848 | doi: 10.1136/bmj-2023-077848
RESEARCH
BMJ: first published as 10.1136/bmj-2023-077848 on 16 November 2023. Downloaded from http://www.bmj.com/ on 1 December 2023 by guest. Protected by copyright.
20 Liu XM, Yang ZM, Liu XK, et al. Intravascular ultrasound-guided drug-
eluting stent implantation for patients with unprotected left main
coronary artery lesions: A single-center randomized trial. Anatol J
Cardiol 2019;21:83-90.
21 Gao XF, Ge Z, Kong XQ, et al, ULTIMATE Investigators. 3-Year
Outcomes of the ULTIMATE Trial Comparing Intravascular Ultrasound
Versus Angiography-Guided Drug-Eluting Stent Implantation. JACC
Cardiovasc Interv 2021;14:247-57. doi:10.1016/j.jcin.2020.10.001
22 Antonsen L, Thayssen P, Maehara A, et al. Optical Coherence
Tomography Guided Percutaneous Coronary Intervention With
Nobori Stent Implantation in Patients With Non-ST-Segment-
Elevation Myocardial Infarction (OCTACS) Trial: Difference
in Strut Coverage and Dynamic Malapposition Patterns at 6
Months. Circ Cardiovasc Interv 2015;8:e002446. doi:10.1161/
CIRCINTERVENTIONS.114.002446
23 Meneveau N, Souteyrand G, Motreff P, et al. Optical Coherence
Tomography to Optimize Results of Percutaneous Coronary
Intervention in Patients with Non-ST-Elevation Acute Coronary
Syndrome: Results of the Multicenter, Randomized DOCTORS
Study (Does Optical Coherence Tomography Optimize Results
of Stenting). Circulation 2016;134:906-17. doi:10.1161/
CIRCULATIONAHA.116.024393
24 Kala P, Cervinka P, Jakl M, et al. OCT guidance during stent
implantation in primary PCI: A randomized multicenter study with
nine months of optical coherence tomography follow-up. Int J
Cardiol 2018;250:98-103. doi:10.1016/j.ijcard.2017.10.059
25 Onuma Y, Kogame N, Sotomi Y, et al, OPTIMUM Investigators. A
Randomized Trial Evaluating Online 3-Dimensional Optical Frequency
Domain Imaging-Guided Percutaneous Coronary Intervention in
Bifurcation Lesions. Circ Cardiovasc Interv 2020;13:e009183.
doi:10.1161/CIRCINTERVENTIONS.120.009183
26 Chamié D, Costa JRJr, Damiani LP, et al. Optical Coherence
Tomography Versus Intravascular Ultrasound and Angiography to
Guide Percutaneous Coronary Interventions: The iSIGHT Randomized
Trial. Circ Cardiovasc Interv 2021;14:e009452. doi:10.1161/
CIRCINTERVENTIONS.120.009452
27 Ali ZA, Karimi Galougahi K, Maehara A, et al. Outcomes of optical
coherence tomography compared with intravascular ultrasound
and with angiography to guide coronary stent implantation:
one-year results from the ILUMIEN III: OPTIMIZE PCI trial.
EuroIntervention 2021;16:1085-91. doi:10.4244/EIJ-D-20-00498
28 Lee JM, Choi KH, Song YB, et al, RENOVATE-COMPLEX-PCI
Investigators. Intravascular Imaging-Guided or Angiography-Guided
Complex PCI. N Engl J Med 2023;388:1668-79. doi:10.1056/
NEJMoa2216607
29 Higgins JPT, Altman DG, Gøtzsche PC, et al, Cochrane Bias Methods
Group, Cochrane Statistical Methods Group. The Cochrane
Collaboration’s tool for assessing risk of bias in randomised trials.
BMJ 2011;343:d5928. doi:10.1136/bmj.d5928
30 Vandenbroucke JP, Pearce N. Incidence rates in dynamic populations.
Int J Epidemiol 2012;41:1472-9. doi:10.1093/ije/dys142
31 Banning AP, Serruys P, De Maria GL, et al. Five-year outcomes after
state-of-the-art percutaneous coronary revascularization in patients
with de novo three-vessel disease: final results of the SYNTAX II study.
Eur Heart J 2022;43:1307-16. doi:10.1093/eurheartj/ehab703
32 Schmid CH, Lau J, McIntosh MW, Cappelleri JC. An empirical study
of the effect of the control rate as a predictor of treatment efficacy
in meta-analysis of clinical trials. Stat Med 1998;17:1923-42.
doi:10.1002/(SICI)1097-0258(19980915)17:17<1923::AID-
SIM874>3.0.CO;2-6
33 Deeks JJ. Issues in the selection of a summary statistic for
meta-analysis of clinical trials with binary outcomes. Stat
Med 2002;21:1575-600. doi:10.1002/sim.1188
34 Furukawa TA, Guyatt GH, Griffith LE. Can we individualize the ‘number
needed to treat’? An empirical study of summary effect measures in
meta-analyses. Int J Epidemiol 2002;31:72-6. doi:10.1093/ije/31.1.72
35 McAlister FA. Commentary: relative treatment effects are
consistent across the spectrum of underlying risks...usually. Int J
Epidemiol 2002;31:76-7. doi:10.1093/ije/31.1.76
36 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin
Trials 1986;7:177-88. doi:10.1016/0197-2456(86)90046-2
37 Turner RM, Davey J, Clarke MJ, Thompson SG, Higgins JP. Predicting
the extent of heterogeneity in meta-analysis, using empirical
data from the Cochrane Database of Systematic Reviews. Int J
Epidemiol 2012;41:818-27. doi:10.1093/ije/dys041
38 Johnson LW, Moore RJ, Balter S. Review of radiation safety
in the cardiac catheterization laboratory. Cathet Cardiovasc
Diagn 1992;25:186-94. doi:10.1002/ccd.1810250304
39 Nikolsky E, Pucelikova T, Mehran R, et al. An evaluation of fluoroscopy
time and correlation with outcomes after percutaneous coronary
intervention. J Invasive Cardiol 2007;19:208-13.
40 Mintz GS, Bourantas CV, Chamié D. Intravascular Imaging for
Percutaneous Coronary Intervention Guidance and Optimization: The
Evidence for Improved Patient Outcomes. J Soc Cardiovasc Angiogr
Interv 2022;1:100413. doi:10.1016/j.jscai.2022.100413.
11
RESEARCH
41 Shrier I, Boivin JF, Steele RJ, et al. Should meta-analyses of
interventions include observational studies in addition to
randomized controlled trials? A critical examination of underlying
principles. Am J Epidemiol 2007;166:1203-9. doi:10.1093/aje/
kwm189
42 Neumann F-J, Sousa-Uva M, Ahlsson A, et al, ESC Scientific Document
Group. 2018 ESC/EACTS Guidelines on myocardial revascularization.
Eur Heart J 2019;40:87-165. doi:10.1093/eurheartj/ehy394
43 Räber L, Mintz GS, Koskinas KC, et al, ESC Scientific Document
Group. Clinical use of intracoronary imaging. Part 1: guidance
and optimization of coronary interventions. An expert consensus
document of the European Association of Percutaneous
Cardiovascular Interventions. Eur Heart J 2018;39:3281-300.
doi:10.1093/eurheartj/ehy285
44 Bass TA, Abbott JD, Mahmud E, et al. 2023 ACC/AHA/SCAI Advanced
Training Statement on Interventional Cardiology (Coronary,
Peripheral Vascular, and Structural Heart Interventions): A Report
of the ACC Competency Management Committee. Circ Cardiovasc
Interv 2023;16:e000088. doi:10.1161/HCV.0000000000000088
12
BMJ: first published as 10.1136/bmj-2023-077848 on 16 November 2023. Downloaded from http://www.bmj.com/ on 1 December 2023 by guest. Protected by copyright.
45 Smilowitz NR, Mohananey D, Razzouk L, Weisz G, Slater JN.
Impact and trends of intravascular imaging in diagnostic coronary
angiography and percutaneous coronary intervention in inpatients
in the United States. Catheter Cardiovasc Interv 2018;92:E410-5.
doi:10.1002/ccd.27673
46 Madder RD, Seth M, Sukul D, et al. Rates of Intracoronary
Imaging Optimization in Contemporary Percutaneous
Coronary Intervention: A Report From the BMC2 Registry.
Circ Cardiovasc Interv 2022;15:e012182. doi:10.1161/
CIRCINTERVENTIONS.122.012182
47 Zhou J, Liew D, Duffy SJ, et al. Intravascular Ultrasound
Versus Angiography-Guided Drug-Eluting Stent
Implantation: A Health Economic Analysis. Circ Cardiovasc
Qual Outcomes 2021;14:e006789. doi:10.1161/
CIRCOUTCOMES.120.006789
Web appendix: Supplementary methods, tables, and
figures
doi: 10.1136/bmj-2023-077848 | BMJ 2023;383:e077848 | the bmj