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Original Research

Contextualizing the BEST-CLI Trial Results in Clinical Practice

Neel M. Butala, MD, MBA

, Venita Chandra, MD

, Joshua A. Beckman, MD

Sahil A. Parikh, MD

, Robert Lookstein, MD

, Sanjay Misra, MD

Eric A. Secemsky, MD, MSc

Division of Cardiology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado;

Division of Vascular Surgery, Department

of Surgery, Stanford University School of Medicine, Palo Alto, California;

Division of Cardiology, Department of Medicine, University of Texas Southwestern

Medical Center, Dallas, Texas;

Division of Cardiology, Department of Medicine, Columbia University School of Medicine, New York, New York;

Department of Radiology, Mt. Sinai School of Medicine, New York, New York;

Department of Radiology, Mayo Clinic, Rochester, Minnesota;

Richard A.

and Susan F. Smith Center for Outcomes Research in Cardiology, Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston,

Massachusetts

ABSTRACT

Background: Chronic limb-threatening ischemia (CLTI) is associated with poor long-term outcomes. Although prompt revascularization is recommended, the

optimal revascularization strategy remains uncertain. The BEST-CLI trial compared endovascular and open surgical revascularization for CLTI, but the

generalizability of this study to the clinical population with CLTI has not been evaluated.

Methods: We included Medicare beneﬁciaries aged 65-85 years with CLTI who underwent revascularization and would be eligible for enrollment in BEST-CLI

between 2016 and 2019. The primary exposure was type of revascularization (endovascular vs autologous graft [cohort 1] vs nonautologous graft [cohort 2]),

and the primary outcome was a composite of major adverse limb events (MALE) and death. MALE included above-ankle amputation and major intervention,

which was deﬁned as new bypass of index limb, thrombectomy, or thrombolysis.

Results: A total of 66,153 patients were included in this study (10,125 autologous grafts; 7867 nonautologous grafts; 48,161 endovascular). Compared with

those enrolled in BEST-CLI cohort 1, patients in this study were older (mean age, 73.5  5.7 vs 69.9  9.9 years), more likely to be female (38.3% [22,340/

58,286] vs 28.5% [408/1434]), and presented with more comorbidities. Endovascular operators for the study population vs BEST-CLI cohort 1 were less likely

to be surgeons (55.9% [26,924/48,148] vs 73.0% [520/708]) and more likely to be cardiologists (25.5% [5900/48,148] vs 14.5% [103/78]). When assessing

long-term outcomes, the crude risk of death or MALE in this cohort was higher with surgery (56.6% autologous grafts vs 42.6% BEST-CLI cohort 1 at a median

of follow-up 2.7 years; 51.6% nonautologous grafts vs 42.8% BEST-CLI cohort 2 at a median follow-up of 1.6 years) but similar with the endovascular cohort

(58.7% Medicare vs 57.4% cohort 1 at 2.7 years; 47.0% Medicare vs 47.7% cohort 2 at 1.6 years). Of those who received endovascular treatment, the risk of

incident major intervention was less than half in this cohort compared with the trial cohort (10.0% Medicare vs 23.5% cohort 1 at 2.7 years; 8.6% Medicare vs

25.6% cohort 2 at 1.6 years), although technical endovascular failures were not captured.

Conclusions: These results suggest that the ﬁndings of the BEST-CLI trial may not be applicable to the entirety of the Medicare population of patients with

CLTI undergoing revascularization.

Introduction

Chronic limb-threatening ischemia (CLTI), the most severe stage of

peripheral artery disease, is associated with poor long-term outcomes.

Although prompt revascularization is recommended in multiple major

societal guidelines,

2,3

the optimal revascularization strategy (surgical vs

endovascular) remains uncertain.

The Best Endovascular Versus Best Surgical Therapy for Patients

with Critical Limb Ischemia (BEST-CLI) trial was a large pragmatic

randomized controlled trial comparing endovascular or open surgical

revascularization for CLTI (cohort 1: single segment of great saphe-

nous vein; cohort 2: alter native bypass conduit).

5,6

However, signif-

icant obstacles, such as potential subject procedural preference,

previous limb stent placement, and excessive risk for surgical

Abbreviations: BEST-CLI, Best Endovascular Versus Best Surgical Therapy for Patients with Critical Limb Ischemia; CLTI, chronic limb-threatening ischemia; CMS, Centers for

Medicare and Medicaid Services; HR, hazard ratio; ICD, International Classiﬁcation of Diseases; MALE, major adverse limb events.

Keywords: chronic limb-threatening ischemia; endovascular; outcomes; revascularization.

* Corresponding author: esecemsk@bidmc.harvard.edu (E.A. Secemsky).

https://doi.org/10.1016/j.jscai.2023.101036

Received 26 April 2023; Received in revised form 27 April 2023; Accepted 28 April 2023

Available online 19 May 2023

the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Journal of the Society for Cardiovascular Angiography & Interventions 2 (2023) 101036

bypass, led to difﬁculties in enrollment,

terminating before meeting

the targeted sample size. With these issues arose concern that the

characteristics of randomized patients, procedural techniques, pro-

portion of patients with suitable surgical risk and venous conduits,

and postprocedural outcomes may differ from that observed in

clinical practice.

Therefore, this study examined patients who underwent revascu-

larization in a sample of Medicare patients who would be eligible for

enrollment to emulate the BEST-CLI trial and evaluate its external

validity.

Methods

Population

All Medicare fee-for-service beneﬁciaries aged 65-85 years between

January 1, 2016, and October 31, 2019, were included if they had

either: (1) an inpatient endovascular or surgical revascularization in the

Centers for Medicare and Medicaid Services (CMS) MedPAR database

based on International Classiﬁcation of Diseases (ICD) 9 or ICD 10 PCS

codes with a primary discharge diagnosis of CLTI; or (2) an outpatient

endovascular procedure in the CMS Carrier and Institutional Outpatient

ﬁles using Current Procedural Terminology codes and a CLTI diagnosis

within the preceding year of the procedure (Supplemental Table 1).

Then, ICD codes were used to mimic the exclusion criteria in the BEST-

CLI trial (Supplemental Table 1). In addition, outpatients from whom

laterality of the procedure could not be determined based on endo-

vascular Current Procedural Terminology codes were excluded. Surgi-

cal bypass codes were stratiﬁed by autologous grafts (cohort 1) and

nonautologous grafts (cohort 2).

Variables

Patient sociodemographics, smoking status, and medical history

were ascertained using the Chronic Conditions Warehouse coding al-

gorithms.

The specialty of physicians performing the procedures

based on taxonomy codes were identiﬁed from physician billing claims.

End points

The primary outcome was a composite of major adverse limb events

(MALE) and death, similar to the BEST-CLI trial.

MALE included

above-ankle amputation and major intervention, which was deﬁned as

new bypass of index limb, thrombectomy, or thrombolysis. Additional

end points included minor intervention, myocardial infarction, and

stroke.

Statistical analysis

Baseline characteristics of patients were compared between revas-

cularization groups using standardized differences. Cumulative in-

cidences for outcomes were examined and differences between groups

were evaluated using Gray test for nondeath outcomes and log-rank

tests for outcomes including death. Adjusted hazard ratios (HRs) were

estimated using Cox regression. Trial sites were identiﬁed in the CMS

database, and patients particularly treated at these sites were

compared with those treated at nontrial sites. A P value of <.05 was

considered signiﬁcant.

Results

A total of 66,153 patients were included in this study (10,125

autologous grafts; 7867 nonautologous grafts; 48,161 endovascular)

(Figure 1). Compared with those enrolled in BEST-CLI cohort 1, this

study cohort of patients revascularized either endovascularly or with

autologous grafts were older (mean age, 73.5  5.7 vs 69.9  9.9 years),

more likely to be female (38.3% [22,340/58,286] vs 28.5% [408/1434]),

and presented with a higher burden of comorbidities (Table 1). In

addition, when comparing treatment strategies within the Medicare

cohort, patients who received endovascular revascularization vs autol-

ogous grafts were more likely to be female (40.0% [19,259/48,161] vs

30.4% [3081/10,125]) and present with an increased frequency of all

comorbidities examined. Similar ﬁndings were observed between

BEST-CLI cohort 2 and the cohort of those revascularized endovascu-

larly or with nonautologous grafts (Supplemental Table 2). Compared

with BEST-CLI cohort 1, endovascular operators in this study were less

likely to be surgeons (55.9% [26,924/48,148] vs 73.0% [520/708]) and

more likely to be cardiologists (25.5% [5900/48,148] vs 14.5% [103/

708]). The proportion of endovascular procedures performed by inter-

ventional radiologists was similar in both BEST-CLI and this population

(12.3% [12,254/48,148] vs 13.4% [95/708]).

When assessing long-term outcomes in comparison with BEST-CLI,

the crude risk of death or MALE in this cohort was higher with surgery

(56.6% autologous grafts vs 42.6% BEST-CLI cohort 1 at a median

follow-up of 2.7 years; 51.6% nonautologous grafts vs 42.8% BEST-CLI

Figure 1.

CONSORT study ﬂow diagram. CLTI, chronic limb-threatening ischemia.

2 N.M. Butala et al. / Journal of the Society for Cardiovascular Angiography & Interventions 2 (2023) 101036

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cohort 2 at a median follow-up of 1.6 years) but similar with endovas-

cular revascularization (58.7% Medicare vs 57.4% cohort 1 at 2.7 years;

47.0% Medicare vs 47.7% cohort 2 at 1.6 years) (Central Illustration and

Tables 2 and 3). Notably, among those receiving endovascular treat-

ment, the frequency of major intervention was less than half in this

cohort compared with the BEST-CLI trial (10.0% Medicare vs 23.5%

cohort 1 at 2.7 years; 8.6% Medicare vs 25.6% cohort 2 at 1.6 years),

although technical endovascular failures were not captured. The fre-

quency of minor intervention was similar (33.5% Medicare vs 33.1%

cohort 1 at 2.7 years; 30.7% Medicare vs cohort 2 32.2% at 1.6 years).

Mortality within 30 days of either procedure was low (4.1% for endo-

vascular; 4.4% for surgery), and early crossover from surgery to endo-

vascular treatment occurred infrequently (3.3% at 90 days).

In adjusted analyses, among patients treated endovascularly or with

autologous grafts, the hazard of MALE or death at a median 3.15 years

was 5% higher with surgery compared with that of endovascular treat-

ment (HR, 1.05; 95% CI, 1.02-1.08) (Table 2). This differed from what

was observed in the BEST-CLI trial (cohort 1: HR, 0.68; 95% CI, 0.59-

0.79). Results were driven primarily by an increased risk of MALE (HR,

1.11; 95% CI, 1.07-1.16). Similar to BEST-CLI, the risk of minor

intervention was signiﬁcantly higher with endovascular treatment (HR,

2.22; 95% CI, 2.13-2.33). The relationship between surgery and MALE

or death was stronger among those who received nonautologous grafts

(HR, 1.21; 95% CI, 1.17-1.24) (Table 3).

Among patients who received care at BEST-CLI trial sites vs those at

nontrial sites, there was no difference in baseline characteristics (Sup-

plemental Table 3); however, the adjusted hazard of primary and select

secondary end points was higher at nontrial sites for both surgical and

endovascular approaches compared with trial sites (Supplemental

Table 4 and Supplemental Figure 1). Furthermore, most of the top

enrolling trial sites treated more Medicare patients than were enrolled

in the BEST-CLI trial (Supplemental Figure 2).

Discussion

In this large study of Medicare patients with CLTI who underwent

revascularization, patients were more often older, females, presented

with more comorbidities, and underwent revascularization by a diversity

of clinical specialties compared with patients treated in the BEST-CLI

Table 1. Baseline characteristics of patients receiving revascularization in BEST-CLI Cohort 1 and Medicare population: autologous graft cohort

Subject characteristic BEST-CLI (cohort 1), n

¼ 1434

Overall, N ¼

58,286

Standardized

difference (%)

Autologous graft, n ¼

10,125

Endovascular, n ¼

48,161

Standardized

difference (%)

Age, y 69.9  9.9 73.5  5.7 60.1 73.2  5.8 73.5  5.7 5.1

Female, % 28.5% (408/1434) 38.3% (22,340/

58,286)

21.2 30.4% (3081/10,125) 40.0% (19,259/

48,161)

20.1

Race/Ethnicity, %

White 72.2% (1028/1423) 75.6% (44,043/

58,286)

10.0 75.1% (7605/10,125) 75.7% (36,438/

48,161)

1.3

Black 19.3% (275/1423) 16.5% (9595/

58,286)

9.8 18.2% (1841/10,125) 16.1% (7754/48,161) 5.5

Asian 1.4% (20/1423) 1.1% (634/

58,286)

1.0 1.1% (112/10,125) 1.1% (522/48,161) 0.2

Other 7.0% (100/1423) 2.6% (1506/

58,286)

18.4 1.9% (194/10,125) 2.7% (1312/48,161) 5.4

Hispanic 13.0% (187/1333) 3.2% (1876/

58,286)

36.8 2.5% (250/10,125) 3.4% (1626/48,161) 5.4

Medical history, %

Hypertension 86.9% (1238/1424) 93.4% (54,459/

58,286)

22.3 80.1% (8109/10,125) 96.2% (46,350/

48,161)

51.6

Hyperlipidemia 73.2% (1041/1423) 87.1% (50,757/

58,286)

35.3 71.8% (7266/10,125) 90.3% (43,491/

48,161)

48.7

Diabetes 71.8% (1023/1424) 79.1% (46,098/

58,286)

23.4 63.7% (6451/10,125) 82.3% (39,647/

48,161)

42.9

Current smoking 35.7% (509/1424) 35.6% (20,766/

58,286)

0.3 32.9% (3333/10,125) 36.2% (17,433/

48,161)

6.9

Coronary artery

disease

43.3% (617/1424) 76.8% (44,782/

58,286)

69.2 62.2% (6302/10,125) 79.9% (38,480/

48,161)

39.7

Congestive heart

failure

5.6% (79/1422) 57.0% (33,204/

58,286)

132.3 39.1% (3956/10,125) 60.7% (29,248/

48,161)

44.4

Stroke 13.3% (190/1424) 46.0% (26,833/

58,286)

75.2 34.0% (3446/10,125) 48.6% (23,387/

48,161)

29.8

COPD 14.6% (208/1424) 27.7% (16,139/

58,286)

31.0 18.6% (1888/10,125) 29.6% (14,251/

48,161)

25.8

End-

stage kidney

disease

10.6% (151/1423) 14.0% (8165/

58,286)

10.0 9.8% (992/10,125) 14.9% (7173/48,161) 15.5

Endovascular operator

Surgeon 73.4% (520/708) 55.9% (26,924/

48,148)

36.3 –––

Interventional

Cardiologist

14.5% (103/708) 25.5% (5900/

48,148)

32.0 –––

Interventional

Radiologist

13.4% (95/708) 12.3% (12,254/

48,148)

2.3 –––

Other 0.4% (3/708) 6.4% (3070/

48,148)

29.0 –––

Values are mean  SD or % (n/N). Standardized difference of >10% suggests imbalance.

COPD, chronic obstructive pulmonary disease.

Represents standardized difference between the BEST-CLI trial and Medicare cohort.

Represents standardized difference between surgery and endovascular in the Medicare cohort.

N.M. Butala et al. / Journal of the Society for Cardiovascular Angiography & Interventions 2 (2023) 101036 3

trial. We found that the cumulative incidence of events for Medicare

patients treated with surgical revascularization was higher than those

observed in BEST-CLI, irrespective of autologous or nonautologous

grafts. Although cumulative endovascular events of the primary end

point were comparable, the frequency of major intervention was less

than half for Medicare patients than observed in the BEST-CLI trial,

albeit technical failures were not captured.

It is notable that our Medicare study differs in many ways from the

BEST-CLI trial results, although most patients with CLTI in the United

States are of Medicare age. Our real-world cohort was older and sicker

than the BEST-CLI trial cohort; however, major patient characteristics

did not differ between Medicare trial and nontrial sites, suggesting the

selective enrollment of healthier patients at trial sites. This was further

supported by trial sites showing better outcomes when compared with

Central Illustration.

Cumulative incidences of the primary and secondary outcomes through complete follow-up by revascularization type. Displayed are the cumulative incidences of the primary

and secondary end points among Medicare patients through a median of 3.15 years of follow-up. For all end points including death, cumulative incidences were estimated using

Kaplan-Meier methods, displaying the numbers at risk. For end points not including death, cumulative incidences were estimated using the cumulative incidence function to consider

the competing risk of death, with no numbers at risk being displayed. (A) MALE or death; (B) death; (C) above-ankle amputation; (D) major intervention; and (E) minor intervention.

MALE, major adverse limb events.

4 N.M. Butala et al. / Journal of the Society for Cardiovascular Angiography & Interventions 2 (2023) 101036

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nontrial sites. Notably, the top enrolling BEST-CLI sites treated few

Medicare patients during the study period. In addition to variations in

the patient population, the treating physician cohort differed as well.

Compared with national practice patterns, vascular surgeons per-

formed signiﬁcantly more of the endovascular procedures in the trial

(73%) compared with that in the real-world population (55.9%).

Short-term outcomes, such as periprocedural death after endovas-

cular treatment and crossover to surgical treatment, were worse in our

Medicare population than observed in the trial cohort. In addition,

major intervention, which contributed the most events to the primary

end point in the BEST-CLI trial, occurred infrequently among real-world

patients undergoing endovascular treatment. We noted that technical

endovascular failures, 15% to 20% in BEST-CLI, could not be captured in

this claims-based study. These differences in observed outcomes be-

tween our Medicare cohort emulation and randomized the BEST-CLI

trial may arise from differences in unobserved baseline characteristics

and lack of equipoise in treatment in this nonrandomized descriptive

study in the Medicare population. Nevertheless, such results provide

valuable complementary evidence to the BEST-CLI trial by answering

important questions on treatment effects in clinical practice.

The

magnitude of differences in the ﬁndings between the trial and the

Medicare cohort is suggestive of the lack of generalizability of this trial’s

ﬁndings to the Medicare population of patients.

These ﬁndings need to be interpreted in context of this study’s

limitations. First, this is an observational study that cannot consider

treatment selection bias. Hence, it is possible that our trial emulation

could experience unmeasured confounding, and our goal was not a

primary analysis comparing endovascular with surgical treatment.

Nonetheless, our results would be biased in favor of surgery given that

endovascular patients likely have an increased unmeasured risk. Sec-

ond, not all patients in this study were likely eligible for the BEST-CLI

trial because clinical equipoise between surgical and endovascular

treatment may occur less frequently among older patients with CLTI,

and our study lacked the anatomical criteria necessary to determine

enrollment eligibility. Third, not all patients in the BEST-CLI trial were

eligible for Medicare, and we were unable to directly compare ﬁndings

in our Medicare cohort of patients with results from only the subset of

BEST-CLI patients eligible for Medicare. Fourth, intervention rates could

be inﬂuenced by less-intensive follow-up that occurs outside of a trial.

Fifth, patient-level data from the BEST-CLI trial were not available;

hence, adjusted analyses between the Medicare population and the

BEST-CLI population could not be performed. Finally, the BEST-CLI

results were based on intention-to-treat population, whereas this anal-

ysis examined an as-treated population.

The BEST-CLI trial enrolled a speciﬁc population of patients with

CLTI, included for low surgical risk and equipoise between endovas-

cular and surgical revascularization. In that enrolled population, the

BEST-CLI trial provides robust evidence regarding the comparative ef-

ﬁcacy of the treatment strategies tested that can inform clinical decision

making. However, the results of this hypothesis-generating descriptive

study suggest that the ﬁndings of the BEST-CLI trial do not mirror what

is found, on average, in a Medicare population of patients with CLTI

undergoing revascularization. These results complement the BEST-CLI

trial and suggest that further analyses in other real-world populations

may be helpful to better contextualize the BEST-CLI trial results to aid

clinicians.

Table 2. Crude cumulative incidence of events and adjusted hazards among the Medicare cohort of patients with CLTI who received revascularization (autologous

grafts).

Outcome Autologous graft, n ¼ 10,125

, % Endovascular, n ¼ 48,161

, % Adjusted hazard ratio: autologous

graft vs endovascular

MALE or death 56.6 (55.5-57.6) 58.7 (58.2-59.1) 1.05 (1.02-1.08) <.001

Death 40.2 (39.1-41.2) 46.8 (46.3-47.3) 0.98 (0.95-1.01) .11

MALE 26.5 (25.6-27.4) 23.9 (23.5-24.3) 1.11 (1.07-1.16) <.001

Above-ankle amputation 18.7 (17.9-19.5) 16.9 (16.5-17.2) 1.11 (1.06-1.17) <.001

Major intervention 12.0 (11.3-12.6) 10.0 (9.8-10.3) 1.20 (1.13-1.28) <.001

Minor intervention 14.5 (13.8-15.2) 33.5 (33.1-34.0) 0.45 (0.43-0.47) <.001

Myocardial infarction 14.8 (14.1-15.6) 17.4 (17.1-17.8) 1.01 (0.96-1.06) .84

Stroke 14.3 (13.7-15.1) 22.1 (21.7-22.5) 0.81 (0.77-0.85) <.001

MALE included above-ankle amputation, new bypass of index limb, thrombectomy, or thrombolysis. Major intervention included new bypass of index limb, throm-

bectomy, or thrombolysis.

CLTI, chronic limb-threatening ischemia; MALE, major adverse limb events.

Cumulative incidence at 2.7 years of follow-up.

Hazard ratios at the complete follow-up (median, 3.15 years), adjusted for all subject characteristics presented in Table 1.

Table 3. Crude cumulative incidence of events and adjusted hazards among Medicare cohort of patients with CLTI who received revascularization (nonautologous

grafts).

Outcomes Nonautologous graft, n ¼ 7867

, % Endovascular, n ¼ 48,161

, % Adjusted hazard ratio: nonautologous

graft vs endovascular

MALE or death 51.2 (50.1-52.3) 47.0 (46.6-47.4) 1.21 (1.17-1.24) <.001

Death 32.7 (31.7-33.8) 33.9 (33.5-34.3) 1.07 (1.04-1.11) <.001

MALE 26.3 (25.3-27.3) 21.1 (20.8-21.5) 1.29 (1.24-1.35) <.001

Above-ankle amputation 17.5 (16.6-18.3) 14.9 (14.6-15.2) 1.24 (1.18-1.31) <.001

Major intervention 12.9 (12.2-13.7) 8.6 (8.4-8.9) 1.51 (1.41-1.60) <.001

Minor intervention 10.5 (9.8-11.2) 30.7 (30.3-31.1) 0.36 (0.34-0.38) <.001

Myocardial infarction 11.7 (11.0-12.4) 13.9 (13.6-14.2) 1.00 (0.94-1.06) .92

Stroke 11.9 (11.2-12.6) 18.8 (18.4-19.1) 0.75 (0.71-0.80) <.001

MALE included above-ankle amputation, new bypass of index limb, thrombectomy, or thrombolysis. Major intervention included new bypass of index limb, throm-

bectomy, or thrombolysis.

CLTI, chronic limb-threatening ischemia; MALE, major adverse limb events.

Cumulative incidence at 1.6 years of follow-up.

Hazard ratios at the complete follow-up (median, 3.15 years), adjusted for all subject characteristics presented in Table 1.

N.M. Butala et al. / Journal of the Society for Cardiovascular Angiography & Interventions 2 (2023) 101036 5

Peer review statement

Associate Editor Sahil A. Parikh had no involvement in the peer

review of this article and has no access to information regarding its peer

review. Full responsibility for the editorial process for this article was

delegated to Editor in Chief Alexandra J. Lansky.

Declaration of competing interest

Eric Secemsky has received consulting fees from Abbott, Bayer, BD,

Boston Scientiﬁc, Cook, Cordis, CSI, Inari, Medtronic, Philips, Shock-

wave, and VentureMed and receives funding from the National Heart,

Lung, and Blood Institute (grant K23HL150290). Sahil Parikh has

received institutional grants/research support from Abbott Vascular,

Shockwave Medical, TriReme Medical, Sumodics, Silk Road Medical,

and the National Institutes of Health; received consulting fees from

Terumo and Abiomed; and served on the Advisory Boards of Abbott,

Medtronic, Boston Scientiﬁc, CSI, Janssen, and Philips. Joshua Beck-

man has received consulting fees from anOne, Janssen, and Novartis

and has ownership in Janacare. Robert Lookstein receives consulting

fees from Boston Scientiﬁc. All other authors have reported that they

have no relationships relevant to the contents of this paper to disclose.

Funding

This research did not receive any speciﬁc grant from funding

agencies in the public, commercial, or not-for-proﬁt sectors.

Ethics statement and patient consent

The study was approved by the institutional review board of Beth

Israel Deaconess Medical Center with a waiver of informed consent for

retrospective data analysis.

Supplementary material

To access the supplementary material accompanying this

article, visit the online version of the Journal of the Society for

Cardiovascular Angiography & Interventions at 10.1016/j.jscai.20

23.101036.

References

1. Abu Dabrh AM, Steffen MW, Undavalli C, et al. The natural history of untreated

severe or critical limb ischemia. J Vasc Surg. 2015;62(6):1642–1651.e3. https://

doi.org/10.1016/j.jvs.2015.07.065

2. Conte MS, Bradbury AW, Kolh P, et al. Global vascular guidelines on the

management of chronic limb-threatening ischemia. J Vasc Surg. 2019;69(6S):

3S–125S.e40. https://doi.org/10.1016/j.jvs.2019.02.016

3. Gerhard-Herman MD, Gornik HL, Barrett C, et al. 2016 AHA/ACC guideline on the

management of patients with lower extremity peripheral artery disease: a report of

the American College of Cardiology/American Heart Association Task Force on

Clinical Practice Guidelines. Circulation. 2017;135(12):e726–e779. https://doi.org/

10.1161/cir.0000000000000471

4. Wang JC, Kim AH, Kashyap VS. Open surgical or endovascular revascularization for

acute limb ischemia. J Vasc Surg. 2016;63(1):270–278. https://doi.org/10.1016/

j.jvs.2015.09.055

5. Menard MT, Farber A, Assmann SF, et al. Design and rationale of the Best

Endovascular Versus Best Surgical Therapy for Patients With Critical Limb Ischemia

(BEST-CLI) trial. J Am Heart Assoc. 2016;5(7):e003219. https://doi.org/10.1161/

jaha.116.003219

6. Farber A, Menard MT, Conte MS, et al. Surgery or endovascular therapy for chronic

limb-threatening ischemia. N Engl J Med. 2022;387(25):2305–2316. https://doi.org/

10.1056/NEJMoa2207899

7. Villarreal MF, Siracuse JJ, M enard M, et al. Enrollment obstacles in a

randomized controlled trial: a performance survey of enrollment in BEST-CLI

sites. Ann Vasc Surg. 2020;62:406–411. https://doi.org/10.1016/j.avsg.2019.

08.069

8. CMS Chronic Conditions Data Warehouse. 30 CCW Chronic Conditions Algorithms.

2022. Accessed December 30, 2022. https://www2.ccwdata.org/documents/10280/

19139421/chr-chronic-condition-algorithms.pdf

9. Wang SV, Schneeweiss S, Franklin JM, et al. Emulation of randomized clinical trials

with nonrandomized database analyses: results of 32 clinical trials. JAMA. 2023;

329(16):1376–1385. https://doi.org/10.1001/jama.2023.4221

6 N.M. Butala et al. / Journal of the Society for Cardiovascular Angiography & Interventions 2 (2023) 101036

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Study Design

Contrast Media Volume Control and Acute Kidney Injury in Acute

Coronary Syndrome: Rationale and Design of the REMEDIAL IV Trial

Carlo Briguori, MD, PhD

, Enrica Mariano, MD

, Alessandro D’Agostino, MD

Mario Scarpelli, MD

, Amelia Focaccio, MD

, Salvatore Evola, MD

Giovanni Esposito, MD, PhD

, Giuseppe Massimo Sangiorgi, MD, PhD

Interventional Cardiology Unit, Mediterranea Cardiocentro, Naples, Italy;

Dipartimento di Biomedicina e Prevenzione, Universit



a Tor Vergata, Rome, Italy;

Division of Cardiology, Paolo Giaccone University Hospital, Palermo, Italy;

Division of Cardiology, Department of Advanced Biomedical Science,

“Federico II” University of Naples, Naples, Italy

ABSTRACT

Background: Although the pathogenesis of acute kidney injury (AKI) in patients with acute coronary syndrome (ACS) unde rgoing invasive treatment is

multifactorial, the role of iodinated contrast media (CM) has been well established. The DyeVert system (Osprey Medical) is designed to reduce the CM volume

during invasive coronary procedures while maintaining ﬂuoroscopic image quality.

Objective: The aim of the Renal Insufﬁciency Following Contrast Media Administration Trial IV (REMEDIAL IV) is to test whether the use of the DyeVert system

is effective in reducing contrast-associated acute kidney injury (CA-AKI) rate in patients with ACS undergoing urgent invasive procedures.

Trial Design: Patients with ACS treated by urgent invasive approach will be enrolled. Participants will be randomly assigned into one of the following groups:

(1) DyeVert group and (2) control group. In participants enrolled in the DyeVert group, CM injection will be handled by the DyeVert system. On the contrary,

in the control group, CM injection will be performed by a conventional manual or automatic injection syringe. In all cases, iobitridol (a low-osmolar, nonionic

CM) will be administered. Participants will receive intravenous 0.9% sodium chloride as soon as moved to the catheterization laboratory. The primary end

points are CM volume administration and CA-AKI rate (ie, an increase in serum creatinine concentration of 0.3 mg/dL within 48 hours after CM exposure). A

sample size of at least 522 randomized participants (261 in each group) is needed to demonstrate an 8.5% difference in the CA-AKI rate between the groups

(that is, from 19% in the control group to 10.5% in the DyeVert group), with a 2-sided 95% conﬁdence interval and 80% power (P < .05).

Introduction

Acute kidney injury (AKI) is a common complication in patients with

acute coronary syndrome (ACS), being treated by invasive approach.

1,2

This complication has been associated with higher early and late

adverse events.

is multifactorial,

the role of iodinated contrast media (CM) has been

well established.

Volume expansion represents the cornerstone in

contrast-associated acute kidney injury (CA-AKI) prevention.

However,

all recommended volume expansion regimens have limited applica-

bility in patients with ST-elevation myocardial infarction (STEMI) and

high-risk non–ST-elevation myocardial infarction (NSTEMI) transferred

to percutaneous coronary intervention (PCI)-capable centers for emer-

gency invasive treatment. Therefore, in this scenario, it is of outmost

importance to limit the CM volume in the attempt to prevent CA-AKI.

The DyeVert system (Osprey Medical) is a novel device designed to

reduce the CM volume during coronary procedures, while maintaining

ﬂuoroscopic image quality.

The aim of the Renal Insufﬁciency Following Contrast Media Admin-

istration Trial IV (REMEDIAL IV) is to test whether the use of the DyeVert

system is effective in reducing AKI rate in patients with ACS undergoing

urgent invasive diagnostic and interventional coronary procedures.

Methods

Recruitment, enrollment, and allocation

This multicenter, randomized, investigator-driven, clinical trial will

assess the role of the DyeVert device in limiting AKI rate in patients

Abbreviations: ACS, acute coronary syndrome; AKI, acute kidney injury; CA-AKI, contrast-associated acute kidney injury; CM, contrast media; GFR, glomerular ﬁltration rate; LVEDP,

left ventricular end-diastolic pressure; NSTEMI, non-ST-elevation myocardial infarction; PCI, percutaneous coronary intervention; sCr, serum creatinine; STEMI, ST-elevation myocardial

infarction.

Keywords: acute coronary syndrome; acute kidney injury; contrast media.

* Corresponding author: carlobriguori@clinicamediterranea.it (C. Briguori).

https://doi.org/10.1016/j.jscai.2023.100980

Received 22 February 2023; Received in revised form 21 March 2023; Accepted 4 April 2023

Available online 28 April 2023

the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Journal of the Society for Cardiovascular Angiography & Interventions 2 (2023) 100980

with ACS. All patients with ACS scheduled for urgent/immediate

invasive approach will be screened for inclusion/exclusion criteria

(Tables 1 and 2). Diagnosis of ACS (both STEMI and hig h-risk NSTEMI)

will be established in accordance with guidelines, including a typical

chest pain history, diagnostic electrocardiographic changes, and serial

increase in cardi ac biomarker concentrations.

8–10

All patients with

inclusion/exclusion criteria satisﬁed and who will agree to sign the

informed consent form will be enrolled into the study. The REMEDIAL

IV will be conducted at 4 Italian interventional cardiology centers

(Supplemental Methods and Supplemental Table S1). Radial access

will be recommended. The study is registered with www.ClinicalT

rials.gov (NCT04714736). The number of participants screened,

treated, and analyzed will be reported according to the CONSORT

guidelines.

Protocol

Participants included into the study will be randomly assigned into 2

groups (Central Illustration): (1) DyeVert group and (2) control group.

The DyeVert group. In participants enrolled in this group, CM injec-

tion will be handled by the DyeVert system. The DyeVert system

(Osprey Medical) is a device designed to reduce the CM volume during

coronary procedures, while maintaining ﬂuoroscopic image quality.

The DyeVert Plus EZ Contrast Reduction Systems is compatible with

manual contrast injection, whereas the DyeVert Power XT Contrast

Reduction System is compatible with automated contrast injection

(ACIST; ACIST Medical Systems). (Supplemental Methods). It allows for

the modulation of the CM volume during an injection. During an in-

jection, the DyeVertsystem diverts a portion of the injected CM through

a secondary ﬂuid pathway controlled by a pressure-compensating

diversion valve. This allows a decrease in overinjection of CM and

less aortic reﬂux. The diversion valve provides variable resistance in the

secondary ﬂuid path to ensure a ﬂow rate to the patient, which results in

an adequate image quality. The valve is constructed in a way that the

diversion pathway resistance automatically increases with higher in-

jection pressures and decreases with lower injection pressures, pro-

portionally decreasing or increasing CM delivered to patients,

respectively. The diverted CM is temporarily stored in the reservoir and

is returned to the injection syringe when the physician aspirates CM for

the next injection. The associated Contrast Monitoring System (Osprey

Medical) displays CM volume injected (in milliliters), split in attempted,

delivered, and saved (the last reported as both absolute value and

percentage vs the total). The DyeVert system can be used in conjunc-

tion with 4F to 6F diagnostic catheters and 5F to 7F guide catheters.

The control group. CM injection in this group will be performed by a

conventional manual injection syringe or automatic injection device

(ACIST Medical Systems).

Iodinated contrast media

Iobitridol (Xenetix 350; Guerbet; 350 mg iodine/mL), a nonionic, low-

osmolality (915 mOsm per kilogram of water) CM, will be used in all

participants. Strategies for limiting the CM volume are as follows

:(1)in

the control group, angiograms will be performed with an injection of CM

using a 10-cm

syringe; this provides strict control of CM delivery by

limiting the volume of contrast that can be administered in a single in-

jection; (2) catheters with side holes will be strictly avoided during PCI; (3)

when exchanging catheters, unused CM is withdrawn from the catheter

lumen (eg, by back-bleeding through an opened “Y”-connector or by

aspirating residual CM from the catheter using a syringe); (4) “tests” with

“puffs” of CM are discouraged; and (5) left ventriculography will not be

permitted. The administration of a CM volume of >3 glomerular

ﬁltration rate (GFR) is suggestive of increased risk of CA-AKI.

AnewCM

source bottle will be used in the control group when using manual sy-

ringe injection to be sure about the starting CM volume level. After the

procedure, the end volume on the CM source bottle will be marked to

indicate the CM volume ending point, and the amount of remaining CM

within the syringe will be documented. Then, the total volume of CM

used from the bottle will be measured using a graduated cylinder.

Volume expansion regimen

Normal saline (0.9% sodium chloride) will be used in all instances. The

volume expansion rate will be 3 mL/kg/h and will start as soon as the

patient will arrive into the catheterization laboratory. Volume expansion

will continue during theprocedureand forat least 6 hours postprocedure.

However, in case of hemodynamic instability (Supplemental Methods

and Supplemental Table S2), volume expansion will be performed

at the rate of 1.5 mL/Kg/h or, if deemed clinically contraindicated,

will not be started at all. Intraprocedural volume expansion will be guided

by left ventricular end-diastolic pressure (LVEDP), according to the Pre-

vention of Contrast Renal Injury with Different Hydration Strategies

(POSEIDON) trial

(Supplemental TableS3). LVEDP measurement will be

made in all patients by placing a 5F or 6F pigtail catheter in the midcavity

of the left ventricle at the beginning of the procedure and before CM

injection. LVEDP will be measured at the beginning of the isometric

ventricular contraction at the“Z” point.A totalvolume expansion of >960

mL is considered the optimal cutoff volume to prevent CA-AKI.

Table 1. Inclusion criteria

Condition Deﬁnition

Age 18 y –

Acute coronary syndrome ST-elevation myocardial infarction

High-risk non–ST-elevation myocardial

infarction

a) Refractory angina

b) Signs or symptoms of heart failure or new or

worsening mitral regurgitation

c) Hemodynamic instability

d) Recurrent angina or ischemia at rest or with

low-level activities despite intensive medical

therapy

e) Sustained VT or VF

f) Recurrent dynamic ST-T wave changes,

particularly with intermittent ST-elevation

Urgent or immediate

(within 2 h) invasive approach

Coronary procedure with iodinated contrast

media administration

VT, ventricular tachycardia; VF, ventricular ﬁbrillation.

According to the Fourth Universal Deﬁnition of Myocardial Infarction.

According to the current guidelines.

9,10

Table 2. Exclusion criteria

Condition Deﬁnition

Women who are pregnant –

Recent contrast media exposure Contrast media exposure

within 48 h

End-stage CKD on chronic dialysis Both hemodialysis and

peritoneal dialysis

Multiple myeloma –

Patients referred from a spoke center for an invasive

treatment but not hospitalized in the institutions

conducting the study

–

Current enrollment in any other study when

enrollment in the REMEDIAL IV would involve

deviation from either protocol

–

CKD, chronic kidney disease; REMEDIAL IV, Renal Insufﬁciency Following

Contrast Media Administration Trial IV.

2 C. Briguori et al. / Journal of the Society for Cardiovascular Angiography & Interventions 2 (2023) 100980

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Biomarkers of renal function and injury

Serum creatinine (sCr), cystatin C, blood urea nitrogen, sodium,

andpotassiumconcentrationswillbemeasuredatthebaseline(ie,as

soon as the participant will arrive in t he emergency room or in the

catheterization laboratory room before CM injection) and every day

during the hospital stay until discharge; additional measurements will

be performed in all cases of deterioration of basel ine renal function.

Estimated GFR will be calculated by applying the Chronic Kidney

Disease Epidemiology Collaboration (CKD-EPI) equation.

Chronic

kidney disease is deﬁned as a GFR of <60 mL/min/1.73 m

.Therisk

scores for predicting CA-AKI will be estimated according to the

Mehran score

and Gurm score

(Supplemental Methods and Sup-

plemental Tables S4 and S5).

Study end points

The primary end point of the trial are CM volume and the rate of AKI,

deﬁned as an increase in a sCr concentration of 0.3 mg/dL within 48

hours after CM administration or the need for dialysis.

Secondary end

points will include the following: (1) an increase in the sCr concentration

of 0.5 and/or 25% mg/dL within 72 hours after CM exposure; (2) the

severity of AKI assessed according to the KDIGO criteria

: stage 1/risk,

a sCr concentration increase of 0.3 mg/dL or 1.5-1.9 times from the

baseline level; stage 2/injury, a sCr concentration increase of 2.0-2.9

times from the baseline; and stage 3/failure, a sCr concentration in-

crease of 3.0 times from the baseline or the need for dialysis; (3)

changes in the serum cystatin C concentration at 24 and 48 hours after

CM exposure; (4) the rate of acute renal failure requiring dialysis

(deﬁned as a decrease in renal function necessitating acute

hemodialysis, ultraﬁltration, or peritoneal dialysis within the ﬁrst 5 days

postintervention); (5) the length of in-hospital stay, calculated as the

sum of the number of days since admission until discharge from the

hospital; (6) the rate of in-hospital and 1-month, 6-month, and 12-month

major adverse events, such as death, major bleeding, renal failure

requiring dialysis, and sustained kidney injury. Major bleeding will be

deﬁned according to the BARC criteria.

Sustained kidney injury is

deﬁned as a persistent 25% GFR reduction, compared with baseline

and the last available value during the follow-up.

Data collection and monitoring

Demographic characteristics, a medical history, and current medi-

cation of all participants will be recorded at the baseline. Totalhydration

volume administered according to the prophylaxis and during 24 and

48 hours after the procedure and the total urine volume will be recor-

ded. The preprocedure sCr level is considered as the baseline value

before the initiation of any prophylaxis. Participant records will include

the presence of clinical parameters of hemodynamic instability. These

include the following: (1) left ventricular ejection fraction (LVEF), (2)

LVEDP, (3) critical state (deﬁned as a cardiogenic shock requiring

treatment with positive inotropes, need for intra-aortic balloon coun-

terpulsation treatment, or mechanical ventilation), (4) heart failure epi-

sodes treated conservatively, (5) clinically signiﬁcant tachyarrhythmias

(ventricular ﬁbrillation, sustained ventricular tachycardia, and atrial

ﬁbrillation), and bradyarrhythmias requiring pacemaker, and (6) major

bleeding. Bleeding will be deﬁned according to the BARC criteria.

Cardiogenic shock will be deﬁned according to the Society for Car-

diovascular Angiography and Interventions (SCAI) classiﬁcation (Sup-

plemental Table S6).

End point data and adverse events will be

Central Illustration.

Schematic representation of the study design. STEMI, ST-elevation myocardial infarction; NSTEMI, non–ST-elevation myocardial infarction; LVEDP, left ventricular end-

diastolic pressure.

C. Briguori et al. / Journal of the Society for Cardiovascular Angiography & Interventions 2 (2023) 100980 3

collected during the in-hospital stay and at 1-month, 6-month, and

12-month major adverse events. All adverse events will be recorded in

the case report form, and the data coordinating center will be informed

by facsimile within 72 hours of any events. Serious events and any other

safety issues will be reviewed by an independent data monitoring and

safety committee. All events will be adjudicated by a clinical events

committee (CEC), blinded to the treatment assignment. At least 2

members of the CEC will review clinical data and relevant documen-

tation and will determine whether end points have occurred according

to the study deﬁnitions. In case of disagreement between the reviewers,

a third member of the CEC will adjudicate, and the data will be

considered by the entire committee if 2 of the 3 reviewers do not agree.

Statistical analysis

Efﬁcacy analyses will be based on an intention-to-treat strategy

deﬁned as all subjects randomly assigned, regardless of the treatment

actually received. Treatment allocation to the 2 groups will be deter-

mined by randomization in a 1:1 ratio. To ensure that almost equal

number of participants will receive one of the 2 treatments, randomi-

zation blocks of 4 will be used. An independent statistician will generate

the randomization list with permuted blocks, and the block size will be

not disclosed to the investigators enrolling the participants (Random

Allocation Software 1.0). Categorical data will be summarized as mean

and standard deviation. Dichotomous outcomes will be compared by

test, using exact procedures. According to the published data, the

expected AKI rate in the control group is 19%.

1–3,21,22

The sample size

has been estimated to test the hypothesis that the reduction in the CM

volume obtained by the DyeVert system would translate into an abso-

lute difference of 8.5% and a 45% relative risk reduction in AKI rate

between the groups.

12,23

Therefore, a sample size of 261 participants in

each group (a total of 522 randomized participants) is needed to

demonstrate an absolute reduction in AKI rate from 19.0% in the control

group to 10.5% in the DyeVert group, with a 2-sided 95% conﬁdence

interval and 80% power (P < .05); based on the large sample normal

approximation extended 0.07 from the observed difference in pro-

portions. The test statistic used will be the 2-sided Fisher exact test. The

signiﬁcance level of the test will be .050. A prespeciﬁed subgroup

analysis includes the following: ACS type (STEMI vs NSTEMI), GFR (<60

vs 60 mL/min/1.73 m

), LVEF (<40% vs 40%), diabetes mellitus,

baseline risk score, hydration volume (<960 vs 960 mL), manual versus

automatic injection, multivessel stent placement, cardiogenic shock,

sex, and age (younger than 75 years vs 75 years or older).

Discussion

Patients with ACS are at high risk of AKI: in this subset of patients,

indeed, the reported AKI rate ranges from 15 to 30%.

1–3,24

The path-

ogenesis of AKI in the setting of ACS is multifactorial. Age, unstable

hemodynamic conditions, comorbidities (ie, diabetes mellitus and

anemia), preexisting chronic renal disease, dehydration, and adminis-

tration of nephrotoxic drugs may concur in the development of AKI.

However, the role of CM has been well established.

Volume expansion represents the cornerstone in CA-AKI preven-

tion.

Currently, there is no consensus on how volume expansion should

be performed, particularly in patients with ACS. The most recom-

mended regimen is normal saline infusion at 1 mL/kg/h (0.5 mL/kg/h if

LVEF 35% or NYHA >2) from 12 hours or before to 24 hours after CM

exposure.

However, this regimen is not suitable in urgent/emergent

settings. Maioli et al

suggested that early rapid volume expansion (3

mL/kg/h starting in the emergency department), followed by infusion of

1 mL/kg/h for 12 hours, allowing to a mean value of almost 1200 mL, is

effective in preventing CA-AKI in STEMI patients. However, this

regimen is contraindicated in patients with ACS and unstable hemo-

dynamic conditions: in this clinical scenario, a forced volume expansion

regimen may increase the risk of pulmonary edema. In the “a Maastricht

contrast-induced nephropathy guideline (AMACING)” trial (which

showed that, in 660 patients deemed to be at risk of CA-AKI, no pro-

phylaxis was noninferior to intravenous hydration for the prevention of

AKI and was also cost-saving), 4% of patients in the hydration group

experienced complications that led to hydration being stopped pre-

maturely. This rate is quite high and unexpected. In studies that enrolled

patients at higher risk of AKI than those included in the AMACING trial,

the reported rate of pulmonary edema was substantially lower

(1%-1.5%).

12,13,22

These ﬁndings reinforce the concept of tailored vol-

ume expansion protocols—a single protocol should not be applied to

all patients. Several tailored volume expansion regimens have been

proposed, such as those guided by LVEDP,

urine ﬂow rate,

central

venous pressure,

and bioimpedence.

All these protocols have been

shown to be superior to the conventional recommended volume

expansion regimen for prevention of CA-AKI and are associated with a

reduced risk of pulmonary edema. In this trial, we will adopt the

LVEDP-guided protocol because this approach is simple and easy to

implement in our target population (ie, patients with ACS undergoing

an invasive approach).

CM volume administered is an independent predictor of CA-AKI.

5,27

Owing to the nonlinear relationship between CM volume and AKI,

some “safe” thresholds have been proposed (Supplemental Table S7).

However, others have reported a linear relationship between CM vol-

ume and AKI rate.

21,28

It has been reported that a 30% reduction in CM

volume could translate into a 12.8% reduction in AKI.

SCAI expert

consensus statement on best practices in the cardiac catheterization

laboratory emphasizes quality indicators related to CM volume reduc-

tion and monitoring.

To date, the use of manual injections with a

manifold remains the preferred technique in most catheterization lab-

oratories.

Although CM ﬂow rate and maximum injection pressure can

be preset in automatic systems, the manual syringe provides constant

pressure feedback to the operator that might favor better modulation of

the injection. The “a clinical trial for contrast media volume reduction

and incidence of CIN” (AVERT) tested the efﬁcacy of the DyeVert sys-

tem to reduce the CM volume used during coronary angiographic

procedures without impairing image quality and to prevent AKI.

The

AVERT trial demonstrated that CM volume is signiﬁcantly lower in pa-

tients receiving DyeVert in comparison with control subjects (36.9 

10.9 mL vs 62.5  12.7 mL; P < .001). This resulted in a 41% decrease in

the volume of CM used. The observed reduction in CM volume used

was most evident in patients who underwent PCI. The volume of CM

spared with the use of AVERTwas directly related to the complexity of

the PCI procedure, with 31% and 46% reductions in CM volume used

when 2 and 3 lesions were treated, respectively.

Other methods for CM volume minimization have been tested.

However, biplane angiography has not been proven to signiﬁcantly

reduce CM volume injected.

Moreover, in the minimizing contrast

utilization with IVUS guidance in coronary angioplasty trial (MOZART),

intravascular ultrasound–guided PCI reduced the CM volume used

compared with angiography-guided PCI.

However, intravascular ul-

trasound is not widely used and can increase procedure costs and

duration.

Preliminary data suggest that the DyeVert system is effective in

reducing CM volume and AKI rate in patients with ACS undergoing

invasive treatment.

The REMEDIAL IV will clarify whether the DyeVert

system is an effective strategy to reduce both CM volume and AKI rate

in patients with ACS undergoing urgent invasive procedures.

Declaration of competing interest

The author(s) declared no potential conﬂicts of interest with respect

to the research, authorship, and/or publication of this article.

4 C. Briguori et al. / Journal of the Society for Cardiovascular Angiography & Interventions 2 (2023) 100980

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