Hydrophilic-coated sheaths for reducing radial artery spasm during transradial procedures: A systematic review and meta-analysis

Abstract

Background

Transradial access for interventional procedures has become increasingly favored over the transfemoral approach. However, radial artery spasm (RAS) and radial artery occlusion (RAO) pose challenges to this approach.

Aims

This study aims to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing hydrophilic coated (HC) introducer sheaths with non-coated (NC) introducer sheaths during transradial procedures. The impact on RAS, RAO, periprocedural pain, and complications is evaluated.

Methods

PubMed, Embase, and the Cochrane Library were searched for RCTs utilizing HC sheaths in their intervention arm and NC sheaths in the control arm for patients undergoing transradial procedures. Outcomes included incidence of RAS, RAO, pain or discomfort during the procedure, procedure duration, pseudoaneurysm, and hematoma. RevMan 5.4 software was used to analyze pooled risk ratios and mean differences with 95% confidence intervals.

Results

Eight RCTs were included in this study. HC sheaths significantly reduced the risk of RAS and periprocedural pain or discomfort compared to NC sheaths (RR = 0.38, 95% CI [0.24, 0.60], I²= 19% and RR = 0.47, 95% CI [0.37, 0.59], I²= 1%, respectively). The use of HC sheaths had no significant effect on the risk of RAO, hematoma, or pseudoaneurysm.

Conclusion

The use of HC sheaths can enhance the overall patient and operator experience by reducing the risk of RAS and pain during transradial procedures, with no significant effect on RAO, hematoma, or pseudoaneurysm. This study provides evidence supporting the superiority of HC introducer sheaths over NC sheaths during transradial interventions.

Introduction

Transradial access (TRA) for interventional procedures has become increasingly favored over the traditional transfemoral approach due to its association with lower morbidity and mortality, enhanced patient comfort, and quicker post-procedural recovery.^1–5 TRA is not without its challenges, with radial artery spasm (RAS) being one of the most common complications that can impede procedural success and cause significant pain to patients.^6,7 RAS occurs in a substantial percentage of TRA procedures and can lead to prolonged procedural times, increased radiation exposure, and failure to complete the intervention in severe cases. ⁷ RAS has been reported to occur in 4% to 35% of transradial procedures.^8–11 Thus, RAS is a common problem encountered with the radial access site that may even necessitate conversion to femoral access. In fact, RAS is the most common cause of TRA site crossover.^8,10 The rates of RAS are higher among females, individuals with shorter height and lower weight, individuals under 65 years of age, individuals with hypertension, diabetes mellitus, anxiety, and smokers.^9,10 Prior studies have identified female sex, small radial artery diameter, and diabetes as independent predictors of RAS.^12,13 RAS has also been identified as a risk factor for radial artery occlusion (RAO), another complication associated with the radial access site. ¹⁴ The risk of RAO is also increased with the use of a larger sheath size. ⁸ Due to collateral circulation between the ulnar and radial arteries supplying the hand, RAO is generally asymptomatic, but it does preclude the use of TRA for subsequent interventions. ¹

One promising strategy to mitigate RAS is the use of hydrophilic-coated (HC) sheaths. These sheaths, designed with a lubricious surface, facilitate smoother insertion and manipulation within the radial artery, potentially reducing the friction and mechanical irritation that contribute to spasm.^15,16 The hydrophilic coating enhances the sheath's maneuverability, minimizing trauma to the arterial wall and thus decreasing the incidence and severity of RAS.^14,16 Two prior randomized controlled trials (RCTs) observed a 50% and 78% reduction in the rate of RAS with the use of HC sheaths, respectively.^14,17 However, three prior RCTs did not find a statistically significant reduction in the incidence of RAS with the use of HC sheaths.^18–20 Thus, the utility and effectiveness of HC sheaths during TRA procedures is not fully appreciated and warrants further investigation.

To our knowledge, there are no systematic reviews or meta-analyses that have investigated the efficacy of HC sheaths in reducing the incidence of RAS, RAO, and patient discomfort during TRA procedures. The goal of this study is to conduct a systematic review and meta-analysis of RCTs that have compared the incidence of RAS, RAO, and patient pain or discomfort in patients undergoing TRA procedures using HC introducer sheaths compared to non-coated (NC) introducer sheaths. The findings will provide valuable insights for interventionalists in the areas of both neurology and cardiology who are seeking to optimize TRA techniques and improve patient care.

Methods

Literature search and screening

The systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. ²¹ The study was registered with PROSPERO: CRD42024535751. We searched PubMed, Embase, and Cochrane library with the following keywords: ((hydrophilic coated sheath) OR (hydrophilic sheath)) AND ((radial artery) OR (radial artery access) OR (transradial access) OR (TRA)) AND (radial artery spasm). We also conducted a non-systematic search in Google Scholar with the same keywords. All retrieved articles were uploaded to the Rayyan software and duplicated were removed using this software. Two independent reviewers (M.H. and K.A.) assessed the articles for eligibility based on title and abstract. Disagreements were resolved by consensus. The remaining articles were then assessed by full-text screening for inclusion in the study by two independent reviewers (M.H. and K.A.) and only articles that met the predefined inclusion criteria were included in the study.

Inclusion and exclusion criteria

We included studies that met the following criteria: RCTs including adult patients over the age of 18 years old undergoing a transradial procedure; intervention arm consisting of a hydrophilic-coated introducer sheath; comparator consisting of a non-coated introducer sheath; one of the following outcomes reported: radial artery spasm, radial artery occlusion, or patient pain/discomfort. Exclusion criteria was studies not in English; studies not involving human subjects; studies not reporting original data; observational studies; review papers; studies with data not available.

Risk of bias assessment

Risk of bias was assessed using the Cochrane Handbook for Systematic Reviews of Interventions for RCTs RoB 2.0 tool. ²² The risk of bias was assessed by two reviewers (M.H. and K.A.) according to the following domains: risk of bias arising from the randomization process, risk of bias due to deviations from the intended interventions, missing outcome data, risk of bias in measurement of the outcome, and risk of bias in selection of the reported result. Based on these domains, the overall risk of bias was reported as either low, high, or some concerns. The risk of bias assessment was displayed using the robvis tool. ²³

Data extraction

Data was extracted by one reviewer (M.H.) and checked for accuracy by two independent reviewers (K.A. and Y.S.). An Excel sheet was used to extract relevant information from studies including study design, main findings, baseline characteristics of study population, and outcome measures reported in raw numbers. The study by Kindel et al. utilized 5-F and 6-F HC and NC sheaths and therefore had two intervention arms and two control arms. ¹⁹ The 5-F and 6-F HC sheath arms were combined in our analysis as the intervention arm, and the 5-F and 6-F NC sheath arms were combined in our analysis as the control arm. The study by Rathore et al. utilized 23 cm and 13 cm HC sheaths and 23 cm and 13 cm NC sheaths and therefore had two intervention arms and two control arms. ¹⁴ The 23 cm and 13 cm HC sheath arms were combined in our analysis as the intervention arm, and the 23 cm and 13 cm NC sheath arms were combined in our analysis as the control arm.

Outcome measures

The efficacy outcomes of interest were incidence of radial artery spasm, incidence of radial artery occlusion, and patient pain or discomfort during the procedure. Safety outcomes included local hematoma, abscess formation, infection, and pseudoaneurysm. Due to inconsistency of reported safety outcomes in the included studies, only hematoma and pseudoaneurysm were pooled and displayed in a forest plot. Other complications such as abscess and infection were only reported by Rathore et al. and were summarized in the results section. Subgrouping was performed on studies using 5-Fr sheaths and 6-Fr sheaths to determine whether HC sheaths reduce the incidence of RAS independent of sheath size. Caussin et al. utilized 5-Fr sheaths whereas Kiemeneij et al., Rathore et al., Saito et al., and Lu et al. utilized 6-Fr sheaths. Kindel et al. included both 5-Fr and 6-Fr sheaths in the intervention and control arms. The study by Lu et al. reported proximal and distal RAO. In order to maintain consistency with the remaining included studies, only distal RAO was included in our analysis.

Data analysis

Data analysis was conducted using RevMan 5.4 software. Data pertaining to the frequency of each outcome was displayed in a forest plot. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using the Mantel–Haenszel test using a random effects model. For continuous variables, mean difference was reported with 95% CI. Heterogeneity was quantified with the I² statistic, with values ≥50% indicating significant heterogeneity. A trial sequential analysis (TSA) was done to assess whether further trials need to be conducted.

Results

Literature search results

Our search strategy yielded a total of 87 articles that were imported into the Rayyan software. Twenty duplicates were removed, yielding a total of 67 articles that were screened based on title and abstract. One additional study was found by a non-systematic search. Fifty-six articles were excluded at this stage, and 12 articles were screened based on full text. Four articles were excluded at this stage, yielding a total of 8 articles that were included in this systematic review and meta-analysis. A summary of the search and screening results is presented in a PRISMA flow diagram in Figure 1.

Figure 1.

PRISMA flow diagram. Flow diagram of study screening and inclusion.

Risk of bias assessment

Risk of bias assessment according to the Cochrane Handbook for Systematic Reviews of Interventions for RCTs RoB 2.0 tool resulted in five studies with low risk of bias (Caussin et al., Kiemeneij et al., Rathore et al., Saito et al., and Lu et al.), and three studies with some concerns (Dery et al., Kindel et al., and Sindberg et al.).^{14,17–20,24,25} The risk of bias summary is presented in Figure 2.

Figure 2.

Risk of bias assessment. Risk of bias was assessed by two independent reviewers according to the five domains; bias arising from the randomization process, bias due to deviations from intended intervention, bias due to missing outcome data, bias in measurement of the outcome, and bias in the selection of the reported result.

Summary of included studies

Eight RCTs comprising 4003 subjects were included in our systematic review and meta-analysis.^{14,17–20,24–26} These RCTs were conducted in France, Canada, The Netherlands, Germany, The United Kingdom, Japan, China, and Denmark. Introducer sheath lengths varied between 7 and 25 cm. All studies utilized HC sheaths in the intervention arm and NC sheaths in the control arm. In all studies, patients were undergoing coronary angiography with or without percutaneous coronary intervention using a transradial approach. With the exception of Lu et al., Rathore et al., and Saito et al., all studies utilized spasmolytic therapy after arterial puncture with nitroglycerin and/or verapamil in both the control and intervention arms. A summary of the included studies and their study design, sample size, inclusion/exclusion criteria, reported outcomes, and main findings is presented in Table 1.

Table 1.

Summary of included studies.

Author, year	Country	Study design	Sample size	Inclusion and exclusion criteria	Intervention	Outcomes reported	Definition of RAS	Spasmolytic therapy	Definition of RAO	Summary/Main findings
Caussin, 2010	France	RCT	Hydrophilic coated sheath = 177 Non-coated sheath = 174	Inclusion: Patients admitted for selective coronary angiography ± coronary intervention. Exclusion: Programmed PCI, coronary bypass catheterization, a negative Allen's test.	25 cm 5 Fr Terumo hydrophilic coated sheath vs. 7 cm 5 Fr Terumo non-coated sheath.	Pain, reported friction, radial artery spasm, radial artery occlusion, catheterization failure, hematoma, procedure failure.	Pain score >4 or presence of friction assessed by operator during catheter manipulation or sheath withdrawal.	1.5–5 mg intraradial verapamil in HC and NC groups.	Complete interruption of pulsed and color echo-Doppler signal the day after procedure.	The hydrophilic sheath resulted in a reduced incidence of radial artery spasm and pain compared to the non-coated sheath. Radial artery occlusion did not differ between the hydrophilic sheath and control sheath.
Dery, 2001	Canada	RCT	Hydrophilic coated sheath = 44 Non-coated sheath = 46	Inclusion: Patients with a patent ulno-palmar arterial arch who were referred for diagnostic coronary angiography or planned angioplasty. Exclusion: Not stated.	19 cm 5 Fr Cook hydrophilic coated sheath vs. 21 cm 5 Fr Namic non-coated sheath.	Peak traction force upon sheath removal, pain, procedure duration.	N/A	10 cc of 250 μg/cc intraradial verapamil in both HC and NC groups.	N/A	The use of the hydrophilic coated sheath resulted in reduced peak traction force during sheath withdrawal and reduced pain during withdrawal compared to the non-coated sheath.
Kiemeneij, 2003	The Netherlands	RCT	Hydrophilic coated sheath = 45 Non-coated sheath = 45	Inclusion: Patients undergoing transradial coronary angioplasty. Exclusion: Patients with a negative Allen's test.	25 cm 6 Fr Radifocus hydrophilic coated sheath vs. 25 cm 6 Fr Radifocus non-coated sheath.	Maximum pullback force, mean pullback force, pain, procedure duration, radial artery spasm.	Friction upon sheath withdrawal and patient pain.	200 μg nitroglycerin and 5 mg verapamil in 10 mL normal saline in both HC and NC groups.	N/A	The use of the hydrophilic coated sheath resulted in decreased pain, and maximum and mean pullback force compared to the non-coated sheath. The use of the hydrophilic coated sheath had no effect on radial artery spasm compared to the non-coated sheath.
Kindel, 2008	Germany	RCT	Hydrophilic coated 5-F sheath = 50 Hydrophilic coated 6-F sheath = 50 Non-coated 5-F sheath = 50 Non-coated 6-F sheath = 50	Inclusion: Patients scheduled for coronary angiography with normal findings on Allen's test. Exclusion: Patients with radial artery diameters <1.7 mm or with radial artery abnormalities.	23 cm hydrophilic coated 5 Fr sheath vs. 23 cm hydrophilic coated 6 Fr sheath vs. 23 cm non-coated 5 Fr sheath vs. 23 cm non-coated 6 Fr sheath.	Radial artery occlusion, radial artery spasm, pain, vascular stenosis, hematoma, local inflammation.	Friction limiting sheath introduction and patient pain.	0.2 mg nitroglycerin and 2 mg verapamil in both HC and NC groups.	Occlusion evidenced by color flow Doppler and two-dimensional ultrasound.	The use of the hydrophilic coated sheath reduced pain but had no effect on radial artery occlusion or radial artery spasm compared to the non-coated sheath.
Rathore, 2010	United Kingdom	RCT	Hydrophilic coated sheath = 397 Non-coated sheath = 393 23 cm long sheath = 396 13 cm short sheath = 394	Inclusion: Patients undergoing coronary catheterization and intervention via the transradial approach. Exclusion: Patients who are hemodynamically unstable, patients with forearm arteriovenous fistulae, patients with chronic renal failure, patients with prior transradial procedures.	23 cm 6 Fr Cook hydrophilic coated sheath vs. 13 cm 6 Fr Cook hydrophilic coated sheath vs. 23 cm 6 Fr Cook non-coated sheath vs. 13 cm 6 Fr Cook non-coated sheath.	Procedure duration, procedural success, radial artery spasm, patient discomfort, radial artery occlusion, large hematoma, noncoronary dissection, late complications.	Difficulty perceived by the operator during insertion, manipulation and/or withdrawal as well as moderate to severe pain perceived by the patient.	Not used.	Absence of palpable radial artery pulsation confirmed by an abnormal reverse Allen test, plethysmography and oximetry test or absent flow signal on handheld Doppler.	The use of the hydrophilic coated sheath resulted in reduced patient discomfort and radial artery spasm compared to the non-coated sheath. There were no differences between short and long sheaths. There was no difference in radial artery occlusion between groups.
Saito, 2002	Japan	RCT	Hydrophilic coated sheath = 37 Non-coated sheath = 36	Inclusion: Patients undergoing transradial coronary intervention. Exclusion: Patients undergoing transfemoral coronary intervention, patients requiring 5, 7, or 8 Fr introducers, patients undergoing emergency transradial coronary intervention, or ad hoc transradial coronary intervention.	16 cm 6 Fr Terumo hydrophilic coated sheath vs. 16 cm 6 Fr Terumo non-coated sheath.	Procedure duration, dynamic friction resistance, ease of insertion grade, radial artery spasm.	Pain perceived by patient during sheath withdrawal.	Not used.	N/A	The use of the hydrophilic coated sheath improved ease of sheath removal but had no effect on radial artery spasm compared to the non-coated sheath.
Sindberg, 2019	Denmark	RCT	Hydrophilic coated sheath = 499 Non-coated sheath = 500	Inclusion: Patients over 18 years of age undergoing transradial coronary angiography or PCI. Exclusion: Abnormal Barbeau test or planned intervention using an 8-F sheath.	10 cm 6 Fr hydrophilic coated Terumo Glidesheath Slender vs. 10 cm 6 Fr non-coated Terumo Radifocus sheath.	Maximal pain during sheath insertion and removal, proportion of patients converted to femoral access, use of analgesics or sedatives, result of reverse Barbeau test, number of catheters used, number of sheaths used.	N/A	0.25 mg nitroglycerin in both HC and NC groups.	Reverse Barbeau test revealing reverse Barbeau type D was interpreted as presence of RAO at discharge. If after 1 month repeat reverse Barbeau test revealed Barbeau type D and arterial ultrasound examination confirmed RAO this was interpreted as RAO at 30 days.	The use of the hydrophilic coated sheath resulted in less pain during sheath insertion with no difference in radial artery occlusion.
Lu, 2024	China	RCT	Hydrophilic coated sheath = 314 Non-coated sheath = 306	Inclusion: 18 years of age with palpable DRA and CRA. Exclusion: 90 years of age or older, height > 185 cm, STEMI or cardiogenic shock, contraindicated for puncture at the planned site, inner diameter of the DRA < 1.5 mm.	6-Fr Hydrophilic coated Terumo Glidesheath Slender vs. 6 Fr non-coated Terumo Radifocus Introducer II sheath	Incidence of RAO, puncture success rate, puncture time, pain during sheath placement, hemostasis time, radial artery dissection, hematoma, numbness.	N/A	Not used.	RAO was evaluated using Doppler ultrasound at 24 h after procedure and defined as disappearance of antegrade blood flow in DRA.	HC sheaths were associated with significantly lower incidence of RAO compared to NC sheaths with no significant differences in any other outcomes.

Abbreviations: RCT, randomized controlled trial; PCI, percutaneous coronary intervention; DRA, distal radial artery; CRA, conventional radial artery; STEMI, ST-elevation myocardial infarction.

The mean age for subjects in the HC sheath arms was 64.57 years (standard deviation (SD) = 11.06 years). The mean age for subjects in the NC sheath arms was 64.98 years (SD = 10.93 years). The mean weight of subjects in the HC sheath and NC sheath arms were 78.85 kg and 79.60 kg, respectively (SD = 14.45 kg and 14.78 kg). The mean height of subjects in the HC sheath and NC sheath arms were 169.2 cm and 169.85 cm, respectively (SD = 9.0 cm and 8.8 cm). The average procedure duration was 35.8 minutes (SD = 22.43 minutes) in the HC sheath arms and 33.3 minutes (SD = 20.1 minutes) in the NC sheath arms. Detailed characteristics of the patient population are provided in Table 2.

Table 2.

Baseline characteristics of patient population.

Study ID	Group	Sample size n	Age Mean (± SD)	Male n (%)	Weight (kg) Mean (± SD)	Height (cm) Mean (± SD)	Body-mass index Mean (± SD)	Radial artery diameter (mm) Mean (± SD)	Procedure duration (minutes) Mean (± SD)	Purpose of procedure	Diabetes n (%)	HTN n (%)	HLD n (%)
Caussin, 2010	HC Sheath	177	66.0 (11.0)	116 (66)	76.0 (15.0)	167.6 (8.6)	26.8 (4.8)	3.0 (0.5)	10.7 (7.4)	CA ± PCI	54 (31)	NR	NR
	NC Sheath	174	66.0 (12.0)	119 (68)	76.0 (15.0)	168.3 (8.9)	26.6 (4.4)	3.1 (0.5)	10.3 (8.1)	CA ± PCI	34 (20)	NR	NR
Dery, 2001	HC Sheath	44	61.1 (10.4)	34 (77)	80.2 (14.4)	168.1 (8.0)	NR	NR	42.1 (27.8)	CA ± PCI	NR	NR	NR
	NC Sheath	46	59.2 (9.4)	37 (80)	78.9 (14.2)	169.5 (7.5)	NR	NR	27.9 (20.7)	CA ± PCI	NR	NR	NR
Kiemeneij, 2003	HC Sheath	45	64.1 (11.4)	33 (73)	75.6 (11.8)	172.0 (9.0)	NR	NR	48.0 (34.0)	CA	NR	NR	NR
	NC Sheath	45	65.0 (12.7)	30 (66)	79.7 (13.7)	173.0 (10.0)	NR	NR	38.0 (26.0)	CA	NR	NR	NR
Kindel, 2008	HC 5F Sheath	50	NR	NR	NR	NR	NR	2.0 (0.1)	NR	CA ± PCI	NR	NR	NR
	NC 5F Sheath	50	NR	NR	NR	NR	NR	2.0 (0.1)	NR	CA ± PCI	NR	NR	NR
	HC 6F Sheath	50	NR	NR	NR	NR	NR	2.6 (0.2)	NR	CA ± PCI	NR	NR	NR
	NC 6F Sheath	50	NR	NR	NR	NR	NR	2.7 (0.3)	NR	CA ± PCI	NR	NR	NR
Rathore, 2010	Long Sheath	396	62.7 (11.5)	293 (74)	83.2 (16.6)	168.7 (10.1)	29.2 (4.8)	NR	50.2 (27.7)	CA ± PCI	68 (17)	275 (69)	360 (91)
	Short Sheath	394	63.0 (10.8)	293 (74)	84.1 (16.2)	169.0 (9.4)	29.4 (5.0)	NR	50.6 (28.9)	CA ± PCI	87 (22)	272 (69)	359 (91)
	HC Sheath	397	62.7 (11.2)	292 (74)	83.6 (16.6)	169.1 (10.4)	29.2 (4.8)	NR	47.4 (26.0)	CA ± PCI	79 (20)	283 (71)	366 (92)
	NC Sheath	393	63.1 (11.1)	294 (75)	83.8 (16.2)	168.6 (9.1)	29.4 (4.9)	NR	53.6 (30.2)	CA ± PCI	76 (19)	264 (67)	353 (90)
Saito, 2002	HC Sheath	37	66.6 (9.8)	29 (78)	NR	NR	NR	2.8 (0.6)	44.9 (18.4)	CA ± PCI	8 (22)	9 (24)	10 (27)
	NC Sheath	36	67.0 (9.2)	26 (72)	NR	NR	NR	2.7 (0.6)	47.5 (15.5)	CA ± PCI	6 (17)	12 (33)	10 (28)
Sindberg, 2019	HC Sheath	499	66.4 (12.0)	NR	NR	NR	27.5 (4.5)	NR	24.0 (21.1)	CA ± PCI	94 (19)	305 (61)	272 (55)
	NC Sheath	500	67.3 (11.6)	NR	NR	NR	27.0 (4.7)	NR	22.6 (18.0)	CA ± PCI	97 (19)	280 (56)	300 (60)
Lu, 2024	HC Sheath	314	67.0 (11.2)	205 (65)	NR	NR	24.8 (3.1)	2.3 (0.5)	33.3 (22.3)	CA ± PCI	100 (32)	231 (74)	21 (7)
	NC Sheath	306	67.7 (10.4)	206 (67)	NR	NR	24.8 (3.3)	2.3 (0.5)	33.3 (22.3)	CA ± PCI	90 (29)	206 (67)	22 (7)

Abbreviations: HC, hydrophilic coated; NC, non-coated; CA, coronary angiography; PCI, percutaneous coronary intervention; HTN, hypertension; HLD, hyperlipidemia; NR, not reported; SD, standard deviation.

Efficacy outcomes

The use of HC sheaths was associated with a 62% reduction in the risk of RAS compared to NC sheaths (RR = 0.38, 95% CI [0.24, 0.60], I²= 19%) (Figure 3A). Subgrouping based on sheath size showed that 5-Fr HC sheaths were associated with a 79% reduction in the risk of RAS compared to 5-Fr NC sheaths (RR = 0.21, 95% CI [0.10, 0.46], I²= 0%) (Figure 3B). 6-Fr HC sheaths were associated with a 52% reduction in the risk of RAS compared to 6-Fr NC sheaths (RR = 0.48, 95% CI [0.38, 0.60], I²= 0%) (Figure 3B). The use of HC sheaths was associated with a 53% reduction in the risk of patient pain/discomfort compared to NC sheaths (RR = 0.47, 95% CI [0.37, 0.59], I²= 1%) (Figure 3C). The use of HC sheaths compared to NC sheaths had no impact on the risk of RAO (RR = 1.05, 95% CI [0.74, 1.49], I² = 11%) (Figure 3D). Subgrouping based on assessment of RAO at discharge (early RAO) and at 1- to 6-month follow-up (late RAO) showed no impact of HC sheaths compared to NC sheaths on RAO at discharge (RR = 0.89, 95% CI [0.52, 1.51], I²= 34%) or at follow-up (RR = 1.28, 95% CI [0.73, 2.27], I²= 0%) (Figure 3D).

Figure 3.

Efficacy outcomes. Pooled results from included studies comparing hydrophilic-coated and non-coated introducer sheaths on the risk of radial artery spasm (A). Subgrouping was performed based on sheath size to determine the risk of radial artery spasm in 5-Fr and 6-Fr hydrophilic-coated and non-coated sheaths (B). Pooled results comparing hydrophilic-coated and non-coated sheaths on the risk of patient pain/discomfort (C). Pooled results comparing hydrophilic-coated and non-coated sheaths on the risk of radial artery occlusion at discharge (early RAO) and at 30-day post-procedure (late RAO) (D).

TSA was conducted on significant comes, RAS (Figure 4) and patient pain/discomfort (Figure 5), to further examine the robustness of the evidence. For both outcomes, we found that the cumulative Z-curve crossed the conventional boundary for benefit, as well as the trial sequential monitoring (TSM) boundary. The expected risk reduction was 62% and 53% for RAS and pain/discomfort, respectively, with an alpha of 5% and power of 80%, indicating the robustness of the obtained evidence. The crossing of both the conventional boundary as well as the TSM boundary indicates that the evidence is conclusive and sufficient (Figures 4 and 5).

Figure 4.

Trial sequential analysis of radial artery spasm. Trial sequential analysis was performed on the outcome of radial artery spasm. TSA is a statistical method used in meta-analyses to determine if the cumulative evidence from multiple trials is conclusive or if more data is needed to avoid errors, ensuring more reliable conclusions. A TSA graph is interpreted by checking whether the cumulative evidence line crosses the predefined boundaries; crossing indicates sufficient evidence for a conclusion, while staying within the boundaries suggests that more data is needed.

Figure 5.

Trial sequential analysis of pain. Trial sequential analysis was performed on the outcome of pain/discomfort during the procedure. TSA is a statistical method used in meta-analyses to determine if the cumulative evidence from multiple trials is conclusive or if more data is needed to avoid errors, ensuring more reliable conclusions. A TSA graph is interpreted by checking whether the cumulative evidence line crosses the predefined boundaries; crossing indicates sufficient evidence for a conclusion, while staying within the boundaries suggests that more data is needed.

Safety outcomes

Five studies reported hematoma as a complication and pooled results showed no difference in hematoma occurrence with the use of HC sheaths compared to NC sheaths (RR = 0.57, 95% CI [0.16, 2.04], I²= 31%) (Figure 6A). Three studies reported pseudoaneurysm as a complication and pooled results showed no difference in pseudoaneurysm occurrence with the use of HC sheaths compared to NC sheaths (RR = 3.05, 95% CI [0.32, 29.03], I²= 0%) (Figure 6B). Caussin et al. reported catheterization failure in 1/177 subjects with HC sheaths and 2/174 subjects with NC sheaths. ¹⁷ Dery et al. reported thrombosis of the radial artery in 1/44 subjects with HC sheaths and 2/46 subjects with NC sheaths, all of which were asymptomatic. ²⁴ Kindel et al. reported local inflammation in 1/100 subjects with HC sheaths and 0/100 subjects with NC sheaths, incomplete sheath insertion in 0/100 subjects with HC sheaths and 3/100 subjects with NC sheaths, and consistent pain for 4-weeks in 0/100 subjects with HC sheaths and 2/100 subjects with NC sheaths. ¹⁹ Rathore et al. reported abscess in 9/397 subjects with HC sheaths and 0/393 subjects with NC sheaths, and infection in 11/397 subjects with HC sheaths and 1/393 subjects with NC sheaths. ¹⁴

Figure 6.

Safety outcomes. Pooled results comparing hydrophilic-coated and non-coated introducer sheaths on the risk of access site hematoma (A) and pseudoaneurysm (B).

Discussion

RAS is a common and significant problem encountered when utilizing the radial access site during interventional procedures. RAS occurs in up to 35% of transradial procedures and can lead to significant pain, prolonged procedure times, vascular injury, access site crossover and procedural failure.^8,10 HC-coated introducer sheaths have been shown to reduce the incidence of RAS during transradial procedures in some studies, however this benefit is uncertain due to discordance in the literature. In this systematic review and meta-analysis, we pooled results from eight RCTs comparing the use of HC-introducer sheaths compared to NC-introducer sheaths during transradial procedures. Pooled results showed that the use of HC sheaths is associated with a 62% reduction in the risk of RAS and 53% reduction in the risk of patient pain and discomfort compared to NC sheaths with no impact on the rate of RAO either at discharge or at 1- to 6-month follow-up. There were no significant differences in the risk of hematoma or pseudoaneurysm with the use of HC sheaths compared to NC sheaths. Subgrouping based on sheath size showed that the risk of RAS was significantly lower in the HC sheath groups in both 5-Fr and 6-Fr subgroups, thus HC sheaths were associated with a reduced risk of RAS compared to NC sheaths independent of sheath size.

Rathore et al. and Caussin et al. reported a significant reduction in the incidence of RAS with the use of HC sheaths compared to NC sheaths which is in agreement with the pooled results of our findings.^14,17 However, the studies by Kindel et al., Saito et al., and Kiemeneij et al. did not find a significant association between the use of HC sheaths and the incidence of RAS.^18–20 Two of these studies were limited by small sample sizes and low incidences of RAS in both the intervention and control groups, which may explain why results failed to reach significance in these studies but were significant in our pooled analysis. The cumulative Z-curve in our TSA crossed both the conventional boundary for benefit and the TSM boundary, indicating sufficient evidence supporting the use of HC sheaths to prevent RAS and patient pain.

Even atraumatic interactions between the catheter surface and the endothelial lining of the blood vessel can cause endothelial cell dysfunction and subsequent vasospasm. ²⁷ Thus, hydrophilic coating may reduce RAS by reducing frictional resistance with catheter sheath insertion and mitigating friction-induced endothelial cell damage. The reduced frictional resistance conferred by hydrophilic coating allows for easier operator maneuverability within the radial artery. In addition to reducing friction-induced damage and vasospasm, hydrophilic coating can improve the comfort of both the patient and the operator during transradial procedures, which has positive implications for patient care. The literature pertaining to the biochemical mechanisms by which hydrophilic coating may reduce the incidence of vasospasm is sparse, and further research in this area is warranted.

Prior studies have shown that the risk of radial access site complications such as spasm and occlusion are higher with 6-Fr sheaths compared to 5-Fr sheaths.^28,29 Our subgroup analysis showed a significantly lower risk of RAS with HC sheaths compared to NC sheaths in both 5-Fr and 6-Fr subgroups, thus the effect of HC sheaths on risk of RAS appears to be independent of sheath size. This is in agreement with the results reported by Kindel et al. which utilized both 5-Fr and 6-Fr sheaths in both the intervention and control groups. ¹⁹ The other included studies kept the sheath size consistent between HC and NC sheath groups, which further supports the notion that the reduced risk of RAS is independent of sheath size. Sheath length may also play a role in the risk of RAS. Long radial sheaths that span the entire length of the radial artery can prevent spasm from contacting the guide catheter beyond the introducer sheath. ³⁰ The mean radial artery length has been reported to be approximately 22.6 cm in men and 20.9 cm in women. ³¹ The lengths of the introducer sheaths used in the studies included in this meta-analysis ranged from 7 to 25 cm. While Caussin et al. attributed the reduction in RAS to the hydrophilic coating of the introducer sheath, it is important to note that this study utilized a 25-cm HC sheath and a 7-cm NC sheath in the intervention and control groups, respectively. ¹⁷ Thus, we cannot be certain that the observed effect was due to the hydrophilic coating or the sheath length. Rathore et al. used 23 cm and 13 cm HC and NC sheaths and found no differences between short and long sheaths. ¹⁴ All other included studies kept sheath length consistent between HC and NC arms, which supports the protective effect of hydrophilic coating on incidence of RAS irrespective of sheath length. We were unable to perform subgroup analysis comparing short versus long HC and NC sheaths on the risk of RAS, as only one of the included studies, the study by Rathore et al., utilized a short sheath in both HC and NC sheath groups.

Out of the eight RCTs included in this meta-analysis, only the study by Rathore et al. reported complications such as abscess and infection and found that there was a significantly higher incidence of local infection and abscess with the use of HC sheaths compared to NC sheaths (5.1% vs 0.3%, respectively, p = 0.001). ¹⁴ Infectious complications from HC or NC sheaths were not reported in the remaining studies. Given that we observed a significant reduction in the risk of RAS and patient pain with the use of HC sheaths compared to NC sheaths, these risks may be outweighed by the benefit of HC sheaths in reducing RAS and periprocedural pain. Indeed, reduction of pain/discomfort with the use of HC sheaths compared to NC sheaths has been consistently reported and is confirmed by the pooled results in this study.

The literature is heavily biased towards cardiac interventions, which is evidenced by the fact that all included studies were performed for either coronary angiography or percutaneous coronary intervention. However, these results are also applicable to neurointerventional procedures as these procedures utilize the same radial access site and similar sheath sizes as those reported in interventional cardiology literature. Diagnostic cerebral angiograms are commonly performed using 5-Fr sheaths. Additionally, 6-Fr guide sheaths are adequate to perform a wide range of neuroendovascular interventions, including mechanical thrombectomies and endovascular management of intracranial aneurysms. ³² A prior study reported that the 5-Fr Cook Shuttle sheath, a hydrophilic-coated sheath, was the most common device used for pediatric neuroendovascular procedures via the transfemoral access site. ³³ It is also common for neurointerventional procedures to utilize 7-Fr sheaths, and our ability to draw conclusions on the efficacy of 7-Fr hydrophilic-coated sheaths in reducing the risk of RAS is limited by the lack of comparative studies utilizing these sheaths in the neurointerventional literature. A recent study investigated the rates of RAO with the use of a 6-Fr Neuron MAX sheath, a non-coated sheath, for the treatment of intracranial aneurysms using the radial artery access site. ³⁴ The authors state that the rigidity of the sheath as well as the absence of outer hydrophilic coating could explain the higher rate of RAO that was observed in this study. ³⁴

Neurointerventional procedures typically involve longer procedural times compared to coronary angiograms or percutaneous coronary interventions. As procedure duration increases, the risk of RAS and RAO also increases, as prolonged access site pressure can exacerbate endothelial damage and vasospasm that leads to RAS and RAO. Thus, the utility of HC sheaths to mitigate frictional forces is especially important in neurointerventional procedures, where prolonged access site pressure can influence complication rates and patient comfort. Additionally, neurointerventional procedures tend to require larger sheath sizes compared to cardiac interventions. The larger sheath sizes used in neurointerventional procedures creates additional challenges for vascular access such as higher rates of spasm or patient discomfort because the larger sheath diameter amplifies the frictional forces acting on the radial artery during the procedure. Thus, the use of HC sheaths may offer greater advantages in the neurointerventional context by decreasing friction between the sheath and the vessel wall.

Chen et al. conducted a multicenter study on the transradial approach for aneurysm treatment that utilized a 6-Fr Terumo Glidesheath Slender introducer sheath, a hydrophilic-coated sheath that was used in several of the included studies in our meta-analysis. This study reported two cases of RAS leading to conversion to femoral access out of a total of 39 patients, and no cases of symptomatic RAO or access site hematomas. ³⁵ Phillips et al. conducted a study on transradial versus transfermoral access for mechanical thrombectomy and utilized a 7-Fr HC introducer sheath during the transradial procedures. ³⁶ Three out of a total of 130 patients (2.3%) in the TRA group had asymptomatic RAO at discharge and no patients had major access site complications. ³⁶ The lack of a control group utilizing a NC introducer sheath prevented our ability to include these two studies in our meta-analysis.

In conclusion, the use of HC introducer sheaths during transradial procedures is associated with a reduction in the risk of RAS and periprocedural pain/discomfort with no significant effect on RAO, pseudoaneurysm, or hematoma when compared to NC sheaths. The relatively low incidence of infection and abscess formation that have been reported in the literature are likely outweighed by the benefit of HC sheaths in reducing RAS and periprocedural pain. By minimizing procedural pain and RAS, HC sheaths may enhance the overall experience of both patients and clinicians. The lack of comparative studies utilizing HC and NC introducer sheaths in the neurointerventional literature is a significant limitation that highlights the need for further research in this area specific to neurological interventions. Nonetheless, the superiority of HC sheaths compared to NC sheaths observed in the cardiology literature is applicable to neurointerventional procedures, and our results suggest that HC coated sheaths should be the sheaths of choice for neurointerventionalists seeking to optimize the TRA approach.

Limitations

This study has several limitations. First, the included studies varied in terms of the brand and size of sheaths used which may have contributed to the heterogeneity observed in our results. Second, the definition of radial artery spasm and radial artery occlusion varied across studies, which may have led to inconsistencies in reporting and pooling of data. Third, several studies did not include long-term follow-up and the studies which had follow-up varied in terms of follow-up duration, which may have impacted the accuracy of the pooled findings. Fourth, the lack of consistency in reporting of safety outcomes such as infection, abscess, and inflammation limited the ability to generate pooled results for these outcomes. We were unable to perform subgroup analysis on short versus long introducer sheaths due to the lack of studies utilizing short sheaths in both HC and NC groups. Four of the eight included studies were published in the same journal, which raises concern for publication bias. The fact that these studies were conducted by different research teams and had varying methodologies helps reduce the risk of bias stemming from a single source or group. Consistent findings despite different methodologies and author groups help to reinforce the reliability of the findings. Due to the limited number of included studies, we were unable to generate a meaningful funnel plot to visually assess publication bias. Also the studies varied in terms of their conclusions (e.g., two studies had nonsignificant findings for RAS, while one study had significant findings and one study did not include RAS as an outcome) also mitigates the likelihood of publication bias. Lastly, the lack of studies in the neurointerventional literature meeting the inclusion and exclusion criteria for this systematic review and meta-analysis limited our ability to include these studies in the meta-analysis.

Impact on daily practice

This study underscores the clinical benefits of HC sheaths in reducing the risk of spasm and pain during transradial procedures with no significant increase in access site complications, which may guide best practice recommendations leading to utilization HC introducer sheaths instead of NC sheaths in clinical practice.

Abbreviations and Acronyms

RAS

radial artery spasm

RAO

radial artery occlusion

HC

hydrophilic-coated

NC

non-coated

TRA

transradial access