†These authors contributed equally.
Academic Editor: Gianluca Rigatelli
Background: Transradial artery (TRA) access for percutaneous coronary
intervention (PCI) was associated with lower risks of major bleeding and vascular
complications compared to transfemoral artery access. Use of large-bore
Transradial access (TRA) has been recommended as the default approach for
diagnostic and interventional cardiovascular procedures because of reduced risk
of vascular and bleeding complications as well as lower rates of mortality and
increased patient comfort . TRA has been shown to be endorsed as the
preferable access strategy in patients undergoing coronary angiography and/or
percutaneous coronary intervention (PCI), with growing recommendations in
guidelines [2, 3, 4, 5, 6]. Altough the risk of complications with TRA are lower than with
the transfemoral access (TFA) approach, and the most frequent complication of TRA
approach is radial artery occlusion (RAO) . Early detection of peri-procedural
RAO (within 24 hours) after PCI and preserving radial artery patency is of
fundamental clinical importance as RAO hampers the use of the radial artery for
future catheterization procedures. At present, large-sized sheath and guiding
The REDUCE-RAO randomized (effect of thin-walled radial sheath for large-bore access on REDUCing pEriprocedural Radial Artery Occlusion following complex PCI) trial was a prospective, single-blind, randomized controlled study that was initiated by the investigator (ClinicalTrials.gov identifier: NCT04748068), in which eligible subjects were randomly assigned in 1:1 fashion to receive either a “7-Fr Glidesheath Slender” or a “7-Fr Cordis sheath”. The present study was approved by the Fuwai Hospital Institutional Review Board. This study followed the Declaration of Helsinki. Before enrollment, all patients gave written informed consent.
The purpose of this trial was to investigate whether 7-Fr Glidesheath Slender is superior to 7-Fr Cordis conventional sheath in patients undergoing complex transradial PCI with respect to periprocedual RAO within 24 hours. As secondary objectives, 7-Fr TRA access with Glidesheath Slender and Cordis sheath for transradial PCI were compared with regard to vascular access site complications, radial artery spasm, procedure success, and the degree of pain at the puncture site.
As the first commercially available 7-Fr thin-walled sheath in China, the 7-Fr Glidesheath Slender (Terumo, Japan) has an inner diameter (ID) of 2.46 mm, compatible with other 7-Fr guiding catheters, with a reduced outer diameter (OD) of 2.79 mm (Supplementary Fig. 1). The 7-Fr Cordis sheath (Avanti+ Catheter Sheath Introducer, Cordis, USA, outer diameter: 3.02 mm) is a standard 7-Fr compatible sheath which is traditionally used in clinical practice in our center.
Local subcutaneous anesthetic with 2% lidocaine was administered to the wrist, 1 to 2 cm proximal to the styloid process of the radial bone, after skin preparation. After placing the introducer 6-Fr sheath (Avanti+ Transradial Kit, Cordis, USA, outer diameter: 2.67 mm), heparin (5000 U) was given as an intra-arterial bolus through the radial sheath. Current standard procedures and recommendations were used to perform transradial coronary angiography.
If 7-Fr guiding catheter was decided to be used by the operator, patients
received an intra-arterial injection of 200
The primary end point was the incidence of peri-procedural RAO (within 24 hours) after complex TRI. Secondary end points were procedural success, vascular access-site complications and pain score (visual analog pain scale 0–10). Visual estimation of a final diameter stenosis of 50% and postprocedural TIMI flow grade 3 in all treated lesions were used to define procedural success. Vascular access-site complications included radial artery spasm, pseudoaneurysm, arteriovenous fistula and local hematoma. Radial artery spasm was described as pain in the forearm that was greater than 6 on a scale of 0 to 10 (numeric pain rating scale) during the procedure, in which patients were asked to state their maximal perceived pain during sheath insertion. An independent clinical event committee whose members were unaware of clinical, angiographic, and procedural data adjudicated all events.
In a prospective multicenter study , the incidence of 1-month RAO in
patients undergoing complex PCI using the TRA method with the 7-Fr Glidesheath
slender was 4.8%. Based on previously studies, incident RAO ranged between 8.5%
and 19% through the TRA approach using the standard 7-Fr sheath and varied with
timing of assessment of radial artery patency [14, 15, 16]. In the present study, the
proportion of patients with early RAO was assumed to be 12% in the standard 7-Fr
Cordis sheath group and 5% in the 7-Fr Glidesheath Slender group. Randomizing
496 recruited patients with a 2-sided level of 0.05 and a maximum 0% rate of
loss to follow-up would provide 80 percent power to establish superiority of the
7-Fr Glidesheath Slender over the 7-Fr Cordis sheath. The mean and standard
deviation of continuous data are presented and compared using the Student’s
t-test. Categorical variables were summarized as counts and percentages,
and Chi-square or Fisher’s exact tests were used to compare them.To find the
possible factors linked to the occurrence of early RAO after TRI, we adopted
univariable and multivariable logistic regression analysis. The baseline
variables with P0.10 in the univariable analysis, as well as any other baseline
factors assessed to be of clinical relevance from previously published
literature, were included in a multivariable logistic regression analysis using a
backward stepwise method, including body mass index (BMI), diabetes, previous
TRI, peripheral artery disease, heparin anticoagulation, procedure duration,
successful PCI, ratio of the sheath outer diameter to the radial artery inner
diameter (S/A), calcium channel blockers (CCB) use, statins use, compression
time, preoperative radial artery diameter, volume of blood flow, and 7-Fr
Glidesheath Slender. All statistical analyses were conducted in both the
intention-to-treat (ITT) population and the as-treated set (ATS). SPSS version
23.0 (SPSS Inc., Chicago, IL, USA) was used for all statistical analyses, and a
From February 2021 to June 2021, previewed through CT angiography or previous coronary angiography, 1018 patients with complex coronary artery disease who would need a 7-Fr guiding catheter before PCI were assessed using radial artery ultrasonography. 76 patients were excluded due to RAO discovered by ultrasonography prior to PCI, 123 patients who did not require interventional therapy, and 315 patients were excluded due to the use of 6-Fr guidance. For the ITT set, a total of 504 patients were included and randomized to either 7-Fr TRA with 7-Fr Glidesheath Slender group (N = 252) or standard 7-Fr Cordis sheath group (N = 252). During PCI procedure, 3 patients in 7-Fr Glidesheath Slender group converted to femoral access for forearm artery deformity and 1 patient in 7-Fr Cordis sheath group converted to femoral access for sheath insertion failure. For the ATS, 249 patients underwent complex PCI with 7-Fr Glidesheath Slender, and 251 patients underwent complex PCI with 7-Fr Cordis sheath (Fig. 1).
Study Flowchart. CTA, CT angiography; CAG, coronary angiography; RAO, radial artery occlusion; ITT, intention-to-treat; ATS, as-treated set.
The baseline characteristics of the research population are shown in Table 1.
There were no significant differences between the groups in terms of demographics
(age, gender, and BMI), coronary artery disease risk factors (diabetes mellitus,
dyslipidemia, and hypertension), clinical presentation, previous TRI history, or
medication during hospitalization. The most commonly treated complex coronary
lesions were CTO (44.4%), followed by bifurcation lesions (23.0%), severe
tortuosity (15.3%), severe calcification (12.3%), and left main disease (5.0%)
(Central Illustration). The ratio of sheath outer diameter and radial artery
inner diameter (S/A) in 7-Fr Glidesheath Slender group was significantly lower
than that in 7-Fr Cordis sheath group (1.12
|Variable||7-Fr Cordis conventional sheath (n = 252)||7-Fr Glidesheath Slender (n = 252)||p value|
|Male||209 (82.9)||216 (85.7)||0.391|
|Hypertension||163 (64.7)||151 (59.9)||0.270|
|Diabetes mellitus||78 (31.0)||92 (36.5)||0.187|
|Hyperlipidemia||247 (98)||250 (99.2)||0.258|
|Current smoker||135 (53.6)||151 (59.9)||0.150|
|Peripheral artery disease||14 (5.6)||18 (7.1)||0.465|
|Previous myocardial infarction||65 (25.8)||65 (25.8)||1.000|
|Previous PCI||87 (34.5)||105 (41.7)||0.099|
|Previous CABG||2 (0.8)||1 (0.4)||0.563|
|Previous stroke||22 (8.7)||18 (7.1)||0.510|
|Previous TRI||149 (59.1)||163 (64.7)||0.199|
|Unstable angina||232 (92.1)||227 (90.1)||0.435|
|NSTEMI||13 (5.2)||12 (4.8)||0.837|
|STEMI||7 (2.8)||13 (5.2)||0.171|
|Medication during hospitalization|
|Oral anticoagulants||3 (1.2)||5 (2.0)||0.476|
|Aspirin||249 (98.8)||252 (100)||0.082|
||248 (98.4)||248 (98.4)||1.000|
|216 (85.7)||225 (89.3)||0.225|
|CCB||79 (31.3)||70 (27.8)||0.380|
|Nitrate||192 (76.2)||199 (79.0)||0.455|
|Nicorandil||83 (32.9)||70 (27.8)||0.208|
|ACEI/ARB||107 (42.5)||106 (42.1)||0.928|
|Statins||249 (98.8)||246 (97.6)||0.313|
|Angiographic and Procedural characteristics|
|Left main||13 (5.2)||12 (4.8)||0.837|
|Bifurcation||51 (20.3)||65 (25.8)||0.138|
|Chronic total occlusion||118 (46.8)||106 (42.1)||0.282|
|Severe calcification||33 (13.1)||29 (11.5)||0.588|
|Severe tortuosity||37 (14.7)||40 (15.9)||0.710|
|Heparin||247 (98.0)||248 (98.4)|
|Bivalirudin||5 (2.0)||4 (1.6)|
|Heparin dose (mg)||80.3
|Procedure duration (min)||72.4
|Contrast volume (mL)||211.0
|Radiation dose (mGy)||2774.9
|Systolic pressure in sheath||148.2
|Diastolic pressure in sheath||78.1
|Ultrasound assessment time (h)||15.2
|Postoperative LMWH||95 (37.7)||81 (32.1)||0.191|
||224 (88.9)||173 (68.7)|
|Values are mean |
By ITT analysis, the primary endpoint of early RAO, as assessed by Ultrasound Doppler imaging in 24 hours after procedure, occurred in 26 (10.3%) patients in the 7-Fr Glidesheath Slender group vs. 34 (13.5%) patients in the 7-Fr Cordis sheath group (p = 0.271) (Table 2 and Fig. 2). There were no symptoms in any of the patients, and there was no evidence of acute hand ischemia. Although statistical superiority was not achieved, 7-Fr Glidesheath Slender was associated to a numerically low incidence of peri-procedural RAO compared to 7-Fr Cordis conventional sheath.
|Variables||7-Fr Cordis conventional sheath (n = 252)||7-Fr Glidesheath Slender (n = 252)||p value|
|Radial artery occlusion||34 (13.5)||26 (10.3)||0.271|
|Procedural success*||236 (93.7)||234 (92.9)||0.722|
|Pain during the procedure†||2.45
|Local hematoma||8 (3.2)||7 (2.8)||0.622|
|Radial spasm||12 (4.8)||6 (2.4)||0.150|
|Arteriovenous fistula||0 (0)||1 (0.4)||1.000|
|Pseudoaneurysm||0 (0)||0 (0)||-|
|Compartment syndrome||0 (0)||0 (0)||-|
|Diameter of right radial artery, mm||2.55
|Maximum velocity, cm/s||78.96
|Minimum velocity, cm/s||16.12
|Average velocity, cm/s||10.24
|Volume of blood flow, mL/s||0.03
|Diameter of right radial artery, mm||3.05
|Maximum velocity, cm/s||70.90
|Minimum velocity, cm/s||14.50
|Average velocity, cm/s||8.07
|Volume of blood flow, mL/s||0.03
|Values are mean |
Incidence of peri-procedural radial artery occlusion by 7-Fr Glidesheath Slender or 7-Fr Cordis sheath.
Procedural success was achieved in 93% of patients. No difference was observed
between 7-Fr Glidesheath Slender and 7-Fr Cordis sheath regarding procedural
success (93.7% vs. 92.9%; p = 0.722) (Fig. 3A). Other secondary
endpoints of access-site complications, including local hematoma, radial spasm,
and arteriovenous fistula were not statistically different between the two groups
(Fig. 3B,C). Although non-significant, the incidence of local hematoma and
radial spasm in 7-Fr Glidesheath Slender group were both numerically lower than
that of the 7-Fr Cordis sheath group. Besides, use of the Glidesheath Slender was
associated with significantly less pain during the procedure (NRS, 2.27
Incidence of other peri-procedural clinical outcome parameters by 7-Fr Glidesheath Slender or 7-Fr Cordis sheath. (A) Procedural success. (B) Local hematoma. (C) Radial spasm. (D) Pain during the procedure (NRS).
Table 2 and Supplementary Fig. 4 shows the radial artery ultrasound
examination parameters before and after TRI. Despite the radial artery diameter
in both groups were larger after procedure, the postoperative radial artery
diameter of 7-Fr Glidesheath Slender group was significantly smaller than the
7-Fr Cordis sheath group (2.97
BMI, peripheral artery disease, heparin dose, the ratio of S/A, preoperative radial artery diameter, CCB use, and volume of blood flow were significantly associated with RAO in univariable logistic regression analysis (Supplementary Table 3). In multivariable regression analysis, independent predictors of RAO were body mass index, peripheral artery disease, heparin anticoagulation, calcium channel blockers use, statins use, and ratio of S/A (Supplementary Table 4).
Our study represents the first randomized trial comparing the efficacy of 7-Fr TRA access with Glidesheath Slender versus Cordis sheath for PCI of complex coronary lesions (Fig. 4). The main findings of the present study can be summarized as follows: (1) the trial failed to demonstrate superiority of 7-Fr Glidesheath Slender for the prevention of early RAO evaluated using Doppler ultrasound within 24 hours after complex PCI procedures through TRA compared with 7-Fr Cordis sheath. (2) Although the 7-Fr Glidesheath Slender was associated with reduced risk of early RAO, the trial did not have enough power to detect a meaningful difference in efficacy outcomes; (3) 7-Fr Glidesheath Slender reduced the pain during the procedure and increase the blood flow velocity of the radial artery assessed by ultrasound, although rates of local hematoma and radial spasm were similar between the groups; (4) routine 7-Fr Glidesheath Slender may not be considered mandatory in RAO prevention in large-bore complex transradial PCI and need to be confirmed in a large-scale randomized trial.
Patient Characteristics, Study Groups, and Important Peri-procedural Clinical Outcome Parameters After PCI of Complex Coronary Lesions Related to the Randomized 7-Fr Sheaths.
Treatment of complex coronary lesions often required specific equipment, such as true bifurcation lesions treated with double-stent technique, left main lesions, heavy calcified lesions requiring rotational atherectomy, severe tortuosity, and CTO lesions requiring several devices simultaneously in one guiding catheter. The use of large-bore sheaths has been documented in 60% to 70% of CTO TRI instances [17, 18]. What’s more, femoral artery cannot be used as operative approach in some patients with severe peripheral vascular disease at lower limbs, neither in some patients with cardiac dysfunction who need to use femoral artery for hemodynamic support, making transradial 7-Fr PCI a rigid demand.
It is known that the use of a large-bore (
In our study, it was revealed that 7-Fr Glidesheath slender was associated to a relatively low peri-procedural RAO (within 12–24 hours) following 7-French TRI compared to standard 7-Fr radial sheaths (10.3% vs. 13.5%, p = 0.271). Previously, a multicenter trial involving 60 consectutive patients have evaluated the safety and feasibility of the 7-Fr Glidesheath slender for complex transradial PCI, which showed a rate of 1-month RAO of 4.8% despite of high procedural success . A prospective multicentre study recruiting patients undergoing left distal transradial approach for coronary CTO interventions using a 7-Fr Glidesheath Slender found the rate of left distal RAO of 4.3% at the 1-month decteced by Doppler ultrasound . Moreover, previous studies have shown that Braidin slender 7-Fr sheath had a RAO rate of 5.8% at 1 month of follow-up in 154 patients with left main bifurcation diseases . Isawa et al.  reported that in the matched patients, the use of 7-Fr Glidesheath slender was significantly less likely to develop ultrasound diagnosed RAO (1.4% vs. 4.1%) at 30 days compared to the use of 7.5-Fr Sheathless system. Notably, the incidence of RAO ranged from a 7.5% incidence during the first 24 hours to 5.5% at 30 days of follow-up [15, 24]. RAO is currently recognized as a barrier to re-intervention in the same radial artery and limits its use as an arterial conduit in patients undergoing coronary artery bypass grafting, or creating an arteriovenous fistula in patients requiring hemodialysis; therefore, prevention of RAO is clinically significant when TRA approach is used.
All participants in our study assessed RAO by Doppler ultrasound within 24 hours. Early dection of RAO at this stage has been considered as the gold-standard method to identify both thrombotic obstruction and lack of flow, where strategies (such as patent hemostasis, adequate anticoagulation and postprocedural hemostatic care) to reduce the incidence of RAO could be implemented [25, 26]. In addition, confirmation of radial artery patency before hospital discharge are suggested to be part of post-PCI patients after TRA approach. As a result, in patients who have invasive procedures through the radial artery, we advocate undertaking an early RAO examination (preferably within 24 hours after PCI or before discharge).
It was reported that 7-Fr Glidesheath slender has the potential to minimize radial artery complications in complex PCI . The use of the hydrophilic coated Slender sheath during radial coronary angiography or PCI was related with decreased pain during sheath insertion . Thus, it seemed reasonable that smaller sheath and thinner sheath coat not only reduce the incidence of early RAO, but also alleviate pain and spasm. The main findings in our study supports this hypothesis. The pain during the procedure in the 7-Fr Glidesheath slender group in our study is significantly lower than that of the Cordis group. Additionally, postoperative ultrasound-doppler assessment of radial artery showed that, patients in the Glidesheath slender group had an apparently higher blood flow velocity than those the standard 7-Fr radial sheath group. This difference may be attributed to the smaller OD of the 7-Fr Glidesheath slender, thus avoid the injury to the radial artery and reduce the inflammation-mediated thickening of the intimal-medial layer.
With regard to the risk factor of RAO, previous trials have demonstrated that
RAO may be related to the following factors such as older age, female gender,
longer procedure times, previous TRI, insufficient unfractionated heparin, narrow
radial artery, and S/A
Prevention of RAO is important from a clinical standpoint and should be a top
priority . Recently, an International Consensus Paper summarized RAO
prevention strategies following percutaneous TRA diagnostic or interventional
procedures , which included (1) reducing the size of the sheath or catheter;
(2) applying adequate procedural anticoagulation; (3) achieving nonocclusive
hemostasis; (4) using a minimal pressure strategy together with shortened
hemostasis time (
This study has several limitations. First, The RAO rate in the 7-Fr slender group (10.3%) in our study was relatively lower than standard 7-Fr group (13.5%). Our original sample size calculation was based on the first prospective registry of complex TRI cases using the 7-Fr Glidesheath Slender to determine the rate of RAO , in which RAO (4.8%) was assessed at 1 month. Resource limitations of the rate of periprocedural RAO after complex PCI prevented us from conducting an event-driven sample size consideration in more accurate pattern. Second, in our study, RAO was assessed during the first 24 hours after complex PCI with TRA access and long-term radial artery patency was not evaluated. This may partly explain the higher rate for periprocedural RAO in the Glidesheath Slender group. However, early detection of RAO in the first 24 hours after TRI is conducive to reopen the radial artery timely . Fourth, local hematomas was not graded in a specific scale (range from type I to type IV) according to the EASY criteria . Fifth, although the average of radial puncture attempt ranged from 1 to 3 times by high-volume and experienced operators, the specific number of radial puncture attempts was not documented in this study. Sixth, this is a single-center study in an academic referral institution with complex PCI expertise [33, 34], and our results may not be generalized to all patients undergoing PCI in other centers and broader populations. Hence, these results will need to be corroborated in multi-centers with more cases in 7-Fr TRI. Finally, other TRA best practices, such as patent hemostasis, minimizing compression time and ipsilateral ulnar compression were not systematically implemented. The higher rate for periprocedural RAO in the Glidesheath Slender group could reflect the superiority criteria for the primary endpoint were not met in the overall trial.
In this prospective, randomized, comparative trial designed to explore the superiority in periprocedural RAO prevention using 7-Fr Glidesheath Slender through TRA for patients undergoing PCI of complex coronary lesions, 7-Fr Glidesheath Slender was not superior to conventional 7-Fr in the prevention of periprocedural RAO within 24 hours following complex PCI, without reducing RAO occurrence. Evaluation of early RAO after complex TRI could facilitate physicians to recanalize RAO by pharmacological and invasive approach for potential future cardiac catheterizations. In aggregate, routine 7-Fr Glidesheath Slender may not be considered mandatory in RAO prevention in large-bore complex transradial PCI and need to be confirmed in a large-scale randomized trial.
HW, H-YW, and K-FD conceived the presented idea and contributed equally to this article. All authors participated in data acquisition and curation. HW, H-YW, and S-YW established the methods and performed the analyses. DY, LF, W-HS, and H-JW took responsible for revising it critically for important intellectual content. K-FD and C-GZ validated the research output. All authors discussed the results and commented on the manuscript. All authors revised the manuscript critically for important intellectual content, agreed for all aspects of the work, and approved the final version to be published.
The study was approved by the ethics committee of Fuwai Hospital (Number: T2020-ZX026) and was conducted in accordance with the Declaration of Helsinki.
This study supported by research grants from the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS) (Grant no. 2021-I2M-1-008), Beijing Health Promotion Association (grant number: 2020-ZX29), Beijing Health Promotion Association (grant number: 2020-ZX52), Beijing Municipal Health Commission-Capital Health Development Research Project (grant number: 2020-1-4032), and Chinese Cardiovascular Association-V.G fund (grant number: 2017-CCA-VG-017). The investigators are solely responsible for the design, conduct, data analysis and interpretation of this study, writing the manuscript, and the decision to submit the ma nuscript for publication, without any influence from the financial supporters.
The authors declare no conflict of interest.
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